A Study to Assess the Efficacy and Safety of BIVV009 (Sutimlimab) in Participants With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion (Cardinal Study)

• ClinicalTrials.gov Identifier: NCT03347396
• Recruitment Status: Completed
• First Posted: November 20, 2017
• Results First Posted: October 31, 2022
• Last Update Posted: October 31, 2022
• Sponsor: Bioverativ, a Sanofi company
• Information provided by (Responsible Party): Sanofi ( Bioverativ, a Sanofi company )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Agglutinin Disease, Cold
• Intervention: Drug: BIVV009
• Enrollment: 24

Participant Flow

Recruitment Details	The study was conducted at 16 active sites in 8 countries. Out of 42 screened participants, a total of 24 participants were enrolled from 05 March 2018 to 10 Jan 2019. This was a single arm study that consisted of 2 Parts: Part A and Part B.
Pre-assignment Details	Participants were stratified based on baseline body weight to receive BIVV009 6.5 grams (g) (if <75 kg) or 7.5 g (if >=75 kg). As planned, data presented as: 1) Dose-wise (2 dose cohorts: BIVV009 6.5 g & BIVV009 7.5 g) for sections, 'disposition, baseline characteristics, safety endpoints & AEs' and 2) combined population (BIVV009) for efficacy endpoints.

Arm/Group Title	BIVV009 6.5 g	BIVV009 7.5 g
Arm/Group Description	Participants with primary cold agglutinin disease (CAD) and body weight less than (<)75 kg with a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an intravenous (IV) infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All participants who completed Part A elected to continue in Part B.	Participants with primary CAD and body weight greater than or equal to (>=)75 kg with a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Period Title: Part A (26 Weeks)
Started	17	7
Completed	16	6
Not Completed	1	1
Reason Not Completed
Adverse Event	1	0
Death	0	1
Period Title: Part B (149 Weeks)
Started	16	6
Completed	14	5
Not Completed	2	1
Reason Not Completed
Adverse Event	1	1
Death	1	0

Baseline Characteristics

Arm/Group Title		BIVV009 6.5 g	BIVV009 7.5 g	Total
Arm/Group Description		Participants with primary CAD and body weight <75 kg with a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All participants who completed Part A elected to continue in Part B.	Participants with primary CAD and body weight >=75 kg with a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.	Total of all reporting groups
Overall Number of Baseline Participants		17	7	24
Baseline Analysis Population Description		Analysis was performed on all enrolled participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	17 participants	7 participants	24 participants
		71.8 (9.05)	70.1 (6.01)	71.3 (8.18)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	17 participants	7 participants	24 participants
	Female	11 64.7%	4 57.1%	15 62.5%
	Male	6 35.3%	3 42.9%	9 37.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	17 participants	7 participants	24 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	3 17.6%	0 0.0%	3 12.5%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	2 11.8%	1 14.3%	3 12.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	12 70.6%	6 85.7%	18 75.0%

Outcome Measures

1. Primary Outcome

Title	Part A: Percentage of Participants With Response to Treatment
Description	A participant was considered a responder: if he or she did not receive a blood transfusion from Week 5 through Week 26 (end of treatment in Part A) and did not receive treatment for CAD beyond what was permitted per protocol. Additionally, the participant's hemoglobin (Hgb) level must meet either of the following criteria: Hgb level >= 12 grams per deciliter (g/dL) at the treatment assessment endpoint (defined as the average of the values from the Week 23, 25, and 26 visits), or Hgb increased >= 2 g/dL from baseline (defined as the last Hgb value before administration of the first dose of study drug) at treatment assessment endpoint. Percentage of responders was calculated together with a 95% exact Clopper-Pearson confidence interval (CI).
Time Frame	From Week 5 through Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part A-full analysis set (FAS) which included all participants who received at least 1 dose (including partial dose) of study drug. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	24
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	54.2; (32.8 to 74.4)

2. Primary Outcome

Title	Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description	An Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TESAEs was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the treatment-emergent (TE) period (from the first investigational medicinal product [IMP] administration in Part B to the last IMP administration + 9 weeks follow up period).
Time Frame	Part B, 6.5 g cohort: From first dose (Week 27) up to 143 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 179); Part B, 7.5 g cohort: From first dose (Week 27) up to 149 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B safety analysis set (SAS) which included all participants who received at least 1 dose (including partial dose) of study drug in Part B. Data for this outcome measures was planned to be collected and analyzed for dose-wise reporting groups (BIVV009 6.5g and BIVV009 7.5 g).

Arm/Group Title	BIVV009 6.5 g	BIVV009 7.5 g
Arm/Group Description:	Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All participants who completed Part A elected to continue in Part B.	Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	16	6
Measure Type: Count of Participants; Unit of Measure: Participants
TEAEs	16 100.0%	6 100.0%
TESAEs	10 62.5%	2 33.3%

3. Secondary Outcome

Title	Part A: Mean Change From Baseline in Bilirubin Levels at the Treatment Assessment Timepoint
Description	Mean change from baseline in bilirubin levels at the treatment assessment timepoint was reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. Least squares (LS) mean and 95% confidence interval (CI) was assessed by Mixed Model for Repeated Measures (MMRM) approach using heterogeneous Toeplitz (TOEPH) covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.
Time Frame	Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	14
Least Squares Mean (95% Confidence Interval); Unit of Measure: micromoles per Liter (mcmol/L)
	-38.18; (-42.52 to -33.84)

4. Secondary Outcome

Title	Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Treatment Assessment Timepoint
Description	FACIT-Fatigue scale consists of 13 questions assessed using a 5-point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question were added to obtain a total score. Total score ranged from 0 to 52, with higher score indicating more fatigue. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.
Time Frame	Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	17
Least Squares Mean (95% Confidence Interval); Unit of Measure: score on a scale
	10.85; (8.00 to 13.70)

5. Secondary Outcome

Title	Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint
Description	Mean change from baseline in LDH at the treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.
Time Frame	Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	17
Least Squares Mean (95% Confidence Interval); Unit of Measure: units per liter
	-126.95; (-218.47 to -35.42)

6. Secondary Outcome

Title	Part A: Number of Blood Transfusions Per Participant
Description	A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the participant had symptoms of anemia or Hgb was <7 g/dL and the participant was asymptomatic. Number of transfusions after the first 5 weeks of study drug administration and up to Week 26 are reported in this outcome measure.
Time Frame	From Week 5 up to Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	23
Mean (Standard Deviation); Unit of Measure: blood transfusions per participant
	0.9 (2.75)

7. Secondary Outcome

Title	Part A: Number of Blood Units Transfused Per Participant
Description	A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: -Hgb was <9 g/dL and the participant had symptoms of anemia or Hgb was <7 g/dL and the participant was asymptomatic. Number of blood units transfused after the first 5 weeks of study drug administration and up to Week 26 are reported in this outcome measure.
Time Frame	From Week 5 up to Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = number of participants with at least 1 transfusion. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	6
Mean (Standard Deviation); Unit of Measure: blood units transfused per participant
	5.8 (8.47)

8. Secondary Outcome

Title	Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint
Description	Mean change from baseline (Week 0) in Hgb at treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.
Time Frame	Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	17
Least Squares Mean (95% Confidence Interval); Unit of Measure: g/dL
	2.60; (0.74 to 4.46)

9. Secondary Outcome

Title	Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points
Description	Change From Hgb level from baseline (Week 0) at each specified time points (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and early termination/safety follow up [ET/SFU] Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame	Baseline, Weeks 27,29,31,33,35,37,39,41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS which included all participants who enrolled in Part B study and received at least 1 dose (including partial dose) of study drug. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title		BIVV009
Arm/Group Description:		Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: g/dL
Week 27	Number Analyzed	22 participants
		2.76 (2.20)
Week 29	Number Analyzed	22 participants
		2.77 (2.20)
Week 31	Number Analyzed	22 participants
		2.74 (1.96)
Week 33	Number Analyzed	22 participants
		2.87 (1.97)
Week 35	Number Analyzed	21 participants
		2.82 (2.10)
Week 37	Number Analyzed	21 participants
		2.71 (2.08)
Week 39	Number Analyzed	21 participants
		2.72 (2.26)
Week 41	Number Analyzed	21 participants
		2.76 (2.24)
Week 43	Number Analyzed	21 participants
		2.73 (2.06)
Week 45	Number Analyzed	21 participants
		2.84 (2.21)
Week 47	Number Analyzed	21 participants
		2.74 (1.95)
Week 49	Number Analyzed	21 participants
		2.73 (2.09)
Week 51	Number Analyzed	22 participants
		2.71 (1.97)
Week 53	Number Analyzed	22 participants
		2.66 (1.97)
Week 55	Number Analyzed	21 participants
		2.73 (1.96)
Week 57	Number Analyzed	21 participants
		3.01 (2.36)
Week 59	Number Analyzed	21 participants
		2.81 (2.10)
Week 61	Number Analyzed	21 participants
		2.88 (2.37)
Week 63	Number Analyzed	21 participants
		2.99 (2.33)
Week 65	Number Analyzed	21 participants
		2.53 (2.18)
Week 67	Number Analyzed	20 participants
		2.52 (2.20)
Week 69	Number Analyzed	20 participants
		2.96 (2.08)
Week 71	Number Analyzed	19 participants
		2.86 (2.31)
Week 73	Number Analyzed	20 participants
		2.79 (2.25)
Week 75	Number Analyzed	21 participants
		2.70 (2.18)
Week 77	Number Analyzed	21 participants
		2.93 (2.59)
Week 79	Number Analyzed	19 participants
		3.13 (2.23)
Week 83	Number Analyzed	20 participants
		2.89 (2.47)
Week 87	Number Analyzed	18 participants
		2.63 (2.36)
Week 91	Number Analyzed	20 participants
		3.23 (2.17)
Week 95	Number Analyzed	19 participants
		3.12 (2.06)
Week 99	Number Analyzed	20 participants
		2.98 (2.01)
Week 103	Number Analyzed	21 participants
		2.92 (2.09)
Week 107	Number Analyzed	21 participants
		2.60 (2.10)
Week 111	Number Analyzed	21 participants
		2.82 (2.17)
Week 115	Number Analyzed	19 participants
		2.96 (2.25)
Week 119	Number Analyzed	20 participants
		2.79 (2.57)
Week 123	Number Analyzed	20 participants
		2.82 (2.35)
Week 127	Number Analyzed	19 participants
		2.89 (1.99)
Week 131	Number Analyzed	19 participants
		3.03 (2.19)
Week 135	Number Analyzed	19 participants
		3.35 (1.99)
Week 139	Number Analyzed	13 participants
		3.42 (2.14)
Week 143	Number Analyzed	11 participants
		3.43 (2.31)
Week 147	Number Analyzed	8 participants
		3.75 (2.38)
Week 151	Number Analyzed	8 participants
		3.43 (1.91)
Week 155	Number Analyzed	8 participants
		3.74 (1.94)
Week 159	Number Analyzed	6 participants
		5.20 (1.65)
Week 163	Number Analyzed	4 participants
		4.18 (1.14)
Week 167	Number Analyzed	2 participants
		4.80 (0.42)
Week 171	Number Analyzed	1 participants
		4.80
Week 175	Number Analyzed	1 participants
		4.40
ET/SFU Visit	Number Analyzed	20 participants
		1.21 (1.56)

10. Secondary Outcome

Title	Part B: Change From Baseline in Bilirubin Levels at Each Specified Time Points
Description	Change from baseline (Week 0) in bilirubin levels at each specified time point (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame	Baseline, Weeks 27,29,31,33,35,37,39,41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title		BIVV009
Arm/Group Description:		Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: mcmol/L
Week 27	Number Analyzed	19 participants
		-34.96 (18.31)
Week 29	Number Analyzed	19 participants
		-34.92 (15.78)
Week 31	Number Analyzed	19 participants
		-32.58 (17.07)
Week 33	Number Analyzed	19 participants
		-32.67 (17.52)
Week 35	Number Analyzed	19 participants
		-32.25 (22.39)
Week 37	Number Analyzed	19 participants
		-33.24 (15.53)
Week 39	Number Analyzed	13 participants
		-35.92 (13.17)
Week 41	Number Analyzed	18 participants
		-35.03 (13.71)
Week 43	Number Analyzed	16 participants
		-36.46 (17.25)
Week 45	Number Analyzed	18 participants
		-34.81 (15.76)
Week 47	Number Analyzed	18 participants
		-34.57 (16.53)
Week 49	Number Analyzed	18 participants
		-32.36 (19.50)
Week 51	Number Analyzed	16 participants
		-34.88 (15.90)
Week 53	Number Analyzed	19 participants
		-35.25 (18.32)
Week 55	Number Analyzed	18 participants
		-34.79 (16.70)
Week 57	Number Analyzed	18 participants
		-36.32 (16.54)
Week 59	Number Analyzed	18 participants
		-35.77 (17.73)
Week 61	Number Analyzed	18 participants
		-36.39 (16.14)
Week 63	Number Analyzed	17 participants
		-38.25 (15.43)
Week 65	Number Analyzed	17 participants
		-35.46 (16.84)
Week 67	Number Analyzed	17 participants
		-35.74 (18.37)
Week 69	Number Analyzed	17 participants
		-33.88 (16.83)
Week 71	Number Analyzed	17 participants
		-32.54 (23.01)
Week 73	Number Analyzed	14 participants
		-33.03 (21.82)
Week 75	Number Analyzed	16 participants
		-30.55 (21.68)
Week 77	Number Analyzed	18 participants
		-30.95 (22.83)
Week 79	Number Analyzed	17 participants
		-35.51 (14.79)
Week 83	Number Analyzed	16 participants
		-38.60 (13.90)
Week 87	Number Analyzed	15 participants
		-37.45 (16.29)
Week 91	Number Analyzed	16 participants
		-35.19 (16.07)
Week 95	Number Analyzed	15 participants
		-33.57 (15.93)
Week 99	Number Analyzed	15 participants
		-28.71 (21.98)
Week 103	Number Analyzed	18 participants
		-32.04 (22.45)
Week 107	Number Analyzed	18 participants
		-34.46 (15.27)
Week 111	Number Analyzed	15 participants
		-37.67 (14.28)
Week 115	Number Analyzed	16 participants
		-36.41 (16.76)
Week 119	Number Analyzed	16 participants
		-34.65 (13.71)
Week 123	Number Analyzed	17 participants
		-29.99 (24.96)
Week 127	Number Analyzed	17 participants
		-35.57 (17.83)
Week 131	Number Analyzed	16 participants
		-35.03 (18.72)
Week 135	Number Analyzed	15 participants
		-36.88 (14.71)
Week 139	Number Analyzed	11 participants
		-37.60 (14.59)
Week 143	Number Analyzed	8 participants
		-44.50 (15.96)
Week 147	Number Analyzed	6 participants
		-44.82 (15.12)
Week 151	Number Analyzed	6 participants
		-46.53 (10.80)
Week 155	Number Analyzed	6 participants
		-50.32 (12.63)
Week 159	Number Analyzed	5 participants
		-46.30 (13.90)
Week 163	Number Analyzed	4 participants
		-46.13 (11.86)
Week 167	Number Analyzed	2 participants
		-36.30 (12.59)
Week 171	Number Analyzed	1 participants
		-32.50
Week 175	Number Analyzed	1 participants
		-29.10
ET/SFU Visit	Number Analyzed	17 participants
		-9.98 (18.11)

11. Secondary Outcome

Title	Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and Early Termination (ET) Visit/Safety Follow-up Visit
Description	FACIT-Fatigue scale consists of 13 questions assessed using a 5-point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question were added to obtain a total score. The Total score ranged from 0 to 52, with higher score indicating more fatigue. Baseline (Week 0) was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame	Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU visit (i.e., up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title		BIVV009
Arm/Group Description:		Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: score on a scale
Week 39	Number Analyzed	19 participants
		9.37 (16.00)
Week 51	Number Analyzed	20 participants
		10.50 (12.05)
Week 63	Number Analyzed	19 participants
		10.21 (11.88)
Week 75	Number Analyzed	19 participants
		11.00 (11.51)
Week 87	Number Analyzed	18 participants
		10.39 (13.41)
Week 99	Number Analyzed	17 participants
		9.94 (8.19)
Week 111	Number Analyzed	18 participants
		9.11 (12.35)
Week 123	Number Analyzed	19 participants
		6.79 (11.28)
Week 135	Number Analyzed	14 participants
		11.71 (13.85)
Week 147	Number Analyzed	7 participants
		13.29 (13.39)
Week 159	Number Analyzed	4 participants
		24.75 (10.24)
Week 171	Number Analyzed	1 participants
		32.00
ET/SFU Visit	Number Analyzed	19 participants
		1.05 (8.15)

12. Secondary Outcome

Title	Part B: Change From Baseline in 12-Item Short-Form Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Each Specified Time Points
Description	SF-12: 12 item-questionnaire assessed health-related quality of life (HRQOL) contained 12 items, categorized into 8 domains (subscales) of functioning and well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality and social functioning, with each domain score ranged from 0 (poor health) to 100 (better health). Higher scores = good health condition. These 8 domains were further summarized into 2 summary scores, PCS and MCS for which, score ranged 0 (poor health) to 100 (better health). Higher scores = better HRQOL. Baseline (Week 0) was defined as the last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Change from baseline in SF-12 PCS and MCS scores is reported in this outcome measure.
Time Frame	Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135 and ET Visit/SFU visit (i.e., up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title		BIVV009
Arm/Group Description:		Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: score on a scale
Week 39-PCS	Number Analyzed	16 participants
		7.813 (10.486)
Week 39-MCS	Number Analyzed	16 participants
		5.859 (10.249)
Week 51-PCS	Number Analyzed	18 participants
		6.677 (9.925)
Week 51-MCS	Number Analyzed	18 participants
		3.912 (9.493)
Week 63-PCS	Number Analyzed	19 participants
		8.318 (7.148)
Week 63-MCS	Number Analyzed	19 participants
		2.385 (9.777)
Week 75-PCS	Number Analyzed	18 participants
		6.580 (9.214)
Week 75-MCS	Number Analyzed	18 participants
		3.102 (9.881)
Week 87-PCS	Number Analyzed	18 participants
		6.398 (9.021)
Week 87-MCS	Number Analyzed	18 participants
		1.611 (10.336)
Week 99-PCS	Number Analyzed	14 participants
		9.054 (5.803)
Week 99-MCS	Number Analyzed	14 participants
		2.581 (9.169)
Week 111-PCS	Number Analyzed	8 participants
		11.958 (3.832)
Week 111-MCS	Number Analyzed	8 participants
		2.523 (12.585)
Week 123-PCS	Number Analyzed	6 participants
		4.743 (6.900)
Week 123-MCS	Number Analyzed	6 participants
		3.810 (14.071)
Week 135-PCS	Number Analyzed	1 participants
		10.450
Week 135-MCS	Number Analyzed	1 participants
		27.900
ET/SFU Visit-PCS	Number Analyzed	1 participants
		-8.920
ET/SFU Visit-MCS	Number Analyzed	1 participants
		-1.180

13. Secondary Outcome

Title	Part B: Change From Baseline in 5-level European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Health State Utility Index and VAS Scores at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU Visit
Description	EQ-5D-5L:standardized, participant-rated questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state utility index (descriptive system) and Visual Analog Scale (VAS). EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response option: no problems, slight problems, moderate problems, severe problems, and extreme problems measured with Likert scale. EQ-5D-5L responses relating to 5 dimensions are converted into a single index utility score between 0 to 1, where higher score=better health state. The EQ-5D-5L VAS rated participant's current health state on a scale from 0=worst imaginable health state to 100 =best imaginable health state. Baseline (Week 0): last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame	Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU visit (i.e., up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title		BIVV009
Arm/Group Description:		Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: score on a scale
Week 39 - Index score	Number Analyzed	18 participants
		0.067 (0.264)
Week 39 - VAS score	Number Analyzed	18 participants
		18.111 (20.642)
Week 51 - Index score	Number Analyzed	20 participants
		0.078 (0.194)
Week 51 - VAS score	Number Analyzed	20 participants
		14.500 (19.050)
Week 63 - Index score	Number Analyzed	19 participants
		0.092 (0.166)
Week 63 - VAS score	Number Analyzed	19 participants
		18.053 (16.844)
Week 75 - Index score	Number Analyzed	19 participants
		0.069 (0.211)
Week 75 - VAS score	Number Analyzed	19 participants
		17.842 (16.604)
Week 87 - Index score	Number Analyzed	19 participants
		0.022 (0.226)
Week 87 - VAS score	Number Analyzed	19 participants
		14.421 (20.815)
Week 99 - Index Score	Number Analyzed	17 participants
		0.060 (0.136)
Week 99 - VAS Score	Number Analyzed	17 participants
		14.059 (13.818)
Week 111 - Index score	Number Analyzed	18 participants
		0.099 (0.174)
Week 111 - VAS score	Number Analyzed	18 participants
		18.889 (15.408)
Week 123 - Index Score	Number Analyzed	19 participants
		0.009 (0.190)
Week 123 - VAS score	Number Analyzed	19 participants
		8.842 (18.765)
Week 135 - Index score	Number Analyzed	15 participants
		0.085 (0.233)
Week 135 - VAS score	Number Analyzed	15 participants
		17.067 (21.608)
Week 147 - Index score	Number Analyzed	7 participants
		0.143 (0.131)
Week 147 - VAS score	Number Analyzed	7 participants
		17.857 (20.178)
Week 159 - Index Score	Number Analyzed	4 participants
		0.250 (0.145)
Week 159 - VAS score	Number Analyzed	4 participants
		36.250 (14.930)
Week 171 - Index score	Number Analyzed	1 participants
		0.535
Week 171 - VAS score	Number Analyzed	1 participants
		35.000
ET/SFU Visit - Index score	Number Analyzed	19 participants
		-0.025 (0.173)
ET/SFU Visit - VAS score	Number Analyzed	19 participants
		1.263 (19.287)

14. Secondary Outcome

Title	Part B: Number of Participants With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU Visit
Description	The PGIS is a self-reported scale. The PGIS is a 1-item questionnaire designed to assess participant's impression of disease severity using a 5-point scale ranging from 1 to 5, where 1=none, 2= mild, 3=moderate, 4=severe, 5=very severe. Higher scores indicated greater severity. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame	At Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU visit (i.e., up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS population. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title		BIVV009
Arm/Group Description:		Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed		22
Measure Type: Count of Participants; Unit of Measure: Participants
Week 39 - None	Number Analyzed	18 participants
		5 27.8%
Week 39 - Mild	Number Analyzed	18 participants
		8 44.4%
Week 39 - Moderate	Number Analyzed	18 participants
		4 22.2%
Week 39 - Severe	Number Analyzed	18 participants
		1 5.6%
Week 39 - Very severe	Number Analyzed	18 participants
		0 0.0%
Week 51 - None	Number Analyzed	21 participants
		5 23.8%
Week 51 - Mild	Number Analyzed	21 participants
		13 61.9%
Week 51 - Moderate	Number Analyzed	21 participants
		3 14.3%
Week 51 - Severe	Number Analyzed	21 participants
		0 0.0%
Week 51 - Very severe	Number Analyzed	21 participants
		0 0.0%
Week 63 - None	Number Analyzed	20 participants
		4 20.0%
Week 63 - Mild	Number Analyzed	20 participants
		12 60.0%
Week 63 - Moderate	Number Analyzed	20 participants
		3 15.0%
Week 63 - Severe	Number Analyzed	20 participants
		1 5.0%
Week 63 - Very severe	Number Analyzed	20 participants
		0 0.0%
Week 75 - None	Number Analyzed	20 participants
		3 15.0%
Week 75 - Mild	Number Analyzed	20 participants
		12 60.0%
Week 75 - Moderate	Number Analyzed	20 participants
		5 25.0%
Week 75 - Severe	Number Analyzed	20 participants
		0 0.0%
Week 75 - Very severe	Number Analyzed	20 participants
		0 0.0%
Week 87 - None	Number Analyzed	19 participants
		5 26.3%
Week 87 - Mild	Number Analyzed	19 participants
		9 47.4%
Week 87 - Moderate	Number Analyzed	19 participants
		3 15.8%
Week 87 - Severe	Number Analyzed	19 participants
		2 10.5%
Week 87 - Very severe	Number Analyzed	19 participants
		0 0.0%
Week 99 - None	Number Analyzed	18 participants
		4 22.2%
Week 99 - Mild	Number Analyzed	18 participants
		10 55.6%
Week 99 - Moderate	Number Analyzed	18 participants
		4 22.2%
Week 99 - Severe	Number Analyzed	18 participants
		0 0.0%
Week 99 - Very severe	Number Analyzed	18 participants
		0 0.0%
Week 111 - None	Number Analyzed	19 participants
		7 36.8%
Week 111 - Mild	Number Analyzed	19 participants
		6 31.6%
Week 111 - Moderate	Number Analyzed	19 participants
		6 31.6%
Week 111 - Severe	Number Analyzed	19 participants
		0 0.0%
Week 111 - Very severe	Number Analyzed	19 participants
		0 0.0%
Week 123 - None	Number Analyzed	20 participants
		4 20.0%
Week 123 - Mild	Number Analyzed	20 participants
		7 35.0%
Week 123 - Moderate	Number Analyzed	20 participants
		7 35.0%
Week 123 - Severe	Number Analyzed	20 participants
		2 10.0%
Week 123 - Very severe	Number Analyzed	20 participants
		0 0.0%
Week 135 - None	Number Analyzed	15 participants
		4 26.7%
Week 135 - Mild	Number Analyzed	15 participants
		8 53.3%
Week 135 - Moderate	Number Analyzed	15 participants
		3 20.0%
Week 135 - Severe	Number Analyzed	15 participants
		0 0.0%
Week 135 - Very severe	Number Analyzed	15 participants
		0 0.0%
Week 147 - None	Number Analyzed	7 participants
		3 42.9%
Week 147 - Mild	Number Analyzed	7 participants
		3 42.9%
Week 147 - Moderate	Number Analyzed	7 participants
		1 14.3%
Week 147 - Severe	Number Analyzed	7 participants
		0 0.0%
Week 147 - Very severe	Number Analyzed	7 participants
		0 0.0%
Week 159 - None	Number Analyzed	4 participants
		3 75.0%
Week 159 - Mild	Number Analyzed	4 participants
		1 25.0%
Week 159 - Moderate	Number Analyzed	4 participants
		0 0.0%
Week 159 - Severe	Number Analyzed	4 participants
		0 0.0%
Week 159 - Very severe	Number Analyzed	4 participants
		0 0.0%
Week 171 - None	Number Analyzed	1 participants
		0 0.0%
Week 171 - Mild	Number Analyzed	1 participants
		1 100.0%
Week 171 - Moderate	Number Analyzed	1 participants
		0 0.0%
Week 171 - Severe	Number Analyzed	1 participants
		0 0.0%
Week 171 - Very severe	Number Analyzed	1 participants
		0 0.0%
ET/SFU Visit - None	Number Analyzed	20 participants
		4 20.0%
ET/SFU Visit - Mild	Number Analyzed	20 participants
		6 30.0%
ET/SFU Visit - Moderate	Number Analyzed	20 participants
		4 20.0%
ET/SFU Visit - Severe	Number Analyzed	20 participants
		5 25.0%
ET/SFU Visit - Very severe	Number Analyzed	20 participants
		1 5.0%

15. Secondary Outcome

Title	Part B: Number of Participants With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU Visit
Description	PGIC is a self-administered questionnaire to evaluate the improvement or worsening compared to the start of the study. PGIC was assessed on a 7-point Likert scale ranged from 1 (greatly improved) to 7 (greatly worsened). Categories were defined based on the PGIC scores as follows: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse and 7=very much worsen. Higher scores indicated greater severity. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame	At Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU visit (i.e., up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title		BIVV009
Arm/Group Description:		Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed		22
Measure Type: Count of Participants; Unit of Measure: Participants
Week 39 - Very much improved	Number Analyzed	19 participants
		9 47.4%
Week 39 - Much improved	Number Analyzed	19 participants
		5 26.3%
Week 39 - Minimally improved	Number Analyzed	19 participants
		3 15.8%
Week 39 - No change	Number Analyzed	19 participants
		1 5.3%
Week 39 - Minimally worse	Number Analyzed	19 participants
		0 0.0%
Week 39 - Much worse	Number Analyzed	19 participants
		1 5.3%
Week 39 - Very much worse	Number Analyzed	19 participants
		0 0.0%
Week 51 - Very much improved	Number Analyzed	21 participants
		6 28.6%
Week 51 - Much improved	Number Analyzed	21 participants
		13 61.9%
Week 51 - Minimally improved	Number Analyzed	21 participants
		2 9.5%
Week 51 - No change	Number Analyzed	21 participants
		0 0.0%
Week 51 - Minimally worse	Number Analyzed	21 participants
		0 0.0%
Week 51 - Much worse	Number Analyzed	21 participants
		0 0.0%
Week 51- Very much worse	Number Analyzed	21 participants
		0 0.0%
Week 63 - Very much improved	Number Analyzed	20 participants
		8 40.0%
Week 63 - Much improved	Number Analyzed	20 participants
		9 45.0%
Week 63 - Minimally improved	Number Analyzed	20 participants
		1 5.0%
Week 63 - No change	Number Analyzed	20 participants
		1 5.0%
Week 63 - Minimally worse	Number Analyzed	20 participants
		1 5.0%
Week 63 - Much worse	Number Analyzed	20 participants
		0 0.0%
Week 63 - Very much worse	Number Analyzed	20 participants
		0 0.0%
Week 75 - Very much improved	Number Analyzed	20 participants
		5 25.0%
Week 75 - Much improved	Number Analyzed	20 participants
		11 55.0%
Week 75 - Minimally improved	Number Analyzed	20 participants
		1 5.0%
Week 75 - No change	Number Analyzed	20 participants
		2 10.0%
Week 75 - Minimally worse	Number Analyzed	20 participants
		1 5.0%
Week 75 - Much worse	Number Analyzed	20 participants
		0 0.0%
Week 75 - Very much worse	Number Analyzed	20 participants
		0 0.0%
Week 87 - Very much improved	Number Analyzed	19 participants
		5 26.3%
Week 87 - Much improved	Number Analyzed	19 participants
		11 57.9%
Week 87 - Minimally improved	Number Analyzed	19 participants
		2 10.5%
Week 87 - No change	Number Analyzed	19 participants
		1 5.3%
Week 87 - Minimally worse	Number Analyzed	19 participants
		0 0.0%
Week 87 - Much worse	Number Analyzed	19 participants
		0 0.0%
Week 87 - Very much worse	Number Analyzed	19 participants
		0 0.0%
Week 99 - Very much improved	Number Analyzed	18 participants
		4 22.2%
Week 99 - Much improved	Number Analyzed	18 participants
		10 55.6%
Week 99 - Minimally improved	Number Analyzed	18 participants
		3 16.7%
Week 99 - No Change	Number Analyzed	18 participants
		1 5.6%
Week 99 - Minimally worse	Number Analyzed	18 participants
		0 0.0%
Week 99 - Much worse	Number Analyzed	18 participants
		0 0.0%
Week 99 - Very much worse	Number Analyzed	18 participants
		0 0.0%
Week 111 - Very much improved	Number Analyzed	19 participants
		7 36.8%
Week 111 - Much improved	Number Analyzed	19 participants
		7 36.8%
Week 111 - Minimally improved	Number Analyzed	19 participants
		5 26.3%
Week 111 - No change	Number Analyzed	19 participants
		0 0.0%
Week 111 - Minimally worse	Number Analyzed	19 participants
		0 0.0%
Week 111 - Much worse	Number Analyzed	19 participants
		0 0.0%
Week 111 - Very much worse	Number Analyzed	19 participants
		0 0.0%
Week 123 - Very much improved	Number Analyzed	20 participants
		8 40.0%
Week 123 - Much improved	Number Analyzed	20 participants
		6 30.0%
Week 123 - Minimally improved	Number Analyzed	20 participants
		6 30.0%
Week 123 - No change	Number Analyzed	20 participants
		0 0.0%
Week 123 - Minimally worse	Number Analyzed	20 participants
		0 0.0%
Week 123 - Much worse	Number Analyzed	20 participants
		0 0.0%
Week 123 - Very much worse	Number Analyzed	20 participants
		0 0.0%
Week 135 - Very much improved	Number Analyzed	15 participants
		5 33.3%
Week 135 - Much improved	Number Analyzed	15 participants
		6 40.0%
Week 135 - Minimally improved	Number Analyzed	15 participants
		2 13.3%
Week 135 - No change	Number Analyzed	15 participants
		1 6.7%
Week 135 - Minimally worse	Number Analyzed	15 participants
		1 6.7%
Week 135 - Much worse	Number Analyzed	15 participants
		0 0.0%
Week 135 - Very much worse	Number Analyzed	15 participants
		0 0.0%
Week 147 - Very much improved	Number Analyzed	7 participants
		4 57.1%
Week 147 - Much improved	Number Analyzed	7 participants
		2 28.6%
Week 147 - Minimally improved	Number Analyzed	7 participants
		1 14.3%
Week 147 - No change	Number Analyzed	7 participants
		0 0.0%
Week 147 - Minimally worse	Number Analyzed	7 participants
		0 0.0%
Week 147 - Much worse	Number Analyzed	7 participants
		0 0.0%
Week 147 - Very much worse	Number Analyzed	7 participants
		0 0.0%
Week 159 - Very much improved	Number Analyzed	4 participants
		4 100.0%
Week 159 - Much improved	Number Analyzed	4 participants
		0 0.0%
Week 159 - Minimally improved	Number Analyzed	4 participants
		0 0.0%
Week 159 - No change	Number Analyzed	4 participants
		0 0.0%
Week 159 - Minimally worse	Number Analyzed	4 participants
		0 0.0%
Week 159 - Much worse	Number Analyzed	4 participants
		0 0.0%
Week 159 - Very much worse	Number Analyzed	4 participants
		0 0.0%
Week 171 - Very much improved	Number Analyzed	1 participants
		1 100.0%
Week 171 - Much improved	Number Analyzed	1 participants
		0 0.0%
Week 171 - Minimally improved	Number Analyzed	1 participants
		0 0.0%
Week 171 - No Change	Number Analyzed	1 participants
		0 0.0%
Week 171 - Minimally worse	Number Analyzed	1 participants
		0 0.0%
Week 171 - Much worse	Number Analyzed	1 participants
		0 0.0%
Week 171 - Very much worse	Number Analyzed	1 participants
		0 0.0%
ET/SFU Visit - Very much improved	Number Analyzed	20 participants
		3 15.0%
ET/SFU Visit - Much improved	Number Analyzed	20 participants
		8 40.0%
ET/SFU Visit - Minimally improved	Number Analyzed	20 participants
		2 10.0%
ET/SFU Visit - No Change	Number Analyzed	20 participants
		4 20.0%
ET/SFU Visit - Minimally worse	Number Analyzed	20 participants
		2 10.0%
ET/SFU Visit - Much worse	Number Analyzed	20 participants
		0 0.0%
ET/SFU Visit - Very much worse	Number Analyzed	20 participants
		1 5.0%

16. Secondary Outcome

Title	Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points
Description	Mean change from baseline in LDH levels at each specified time points (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and ET/SFU Visit) is reported in this outcome measure. Baseline (Week 0) was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame	Baseline, Weeks 27,29,31,33,35,37,39,41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title		BIVV009
Arm/Group Description:		Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: units per liter
Week 27	Number Analyzed	22 participants
		-111.59 (327.80)
Week 29	Number Analyzed	21 participants
		-129.76 (331.91)
Week 31	Number Analyzed	22 participants
		-95.27 (319.25)
Week 33	Number Analyzed	21 participants
		-82.19 (330.04)
Week 35	Number Analyzed	22 participants
		-126.64 (346.75)
Week 37	Number Analyzed	21 participants
		-151.57 (307.15)
Week 39	Number Analyzed	15 participants
		-49.27 (172.53)
Week 41	Number Analyzed	21 participants
		-116.10 (305.11)
Week 43	Number Analyzed	19 participants
		-150.26 (271.72)
Week 45	Number Analyzed	21 participants
		-85.48 (308.01)
Week 47	Number Analyzed	21 participants
		-79.81 (286.13)
Week 49	Number Analyzed	21 participants
		-104.38 (313.66)
Week 51	Number Analyzed	19 participants
		-76.84 (344.60)
Week 53	Number Analyzed	21 participants
		-87.00 (299.09)
Week 55	Number Analyzed	21 participants
		-68.29 (305.09)
Week 57	Number Analyzed	21 participants
		-101.71 (273.44)
Week 59	Number Analyzed	21 participants
		-97.71 (296.74)
Week 61	Number Analyzed	21 participants
		-89.48 (298.05)
Week 63	Number Analyzed	20 participants
		-94.20 (288.34)
Week 65	Number Analyzed	20 participants
		-91.05 (305.75)
Week 67	Number Analyzed	19 participants
		-106.32 (327.48)
Week 69	Number Analyzed	19 participants
		-75.00 (333.47)
Week 71	Number Analyzed	18 participants
		-52.39 (378.82)
Week 73	Number Analyzed	17 participants
		-70.35 (348.56)
Week 75	Number Analyzed	19 participants
		-18.68 (323.02)
Week 77	Number Analyzed	21 participants
		-64.67 (335.73)
Week 79	Number Analyzed	20 participants
		-54.10 (338.58)
Week 83	Number Analyzed	19 participants
		-87.21 (344.88)
Week 87	Number Analyzed	18 participants
		-89.17 (392.80)
Week 91	Number Analyzed	19 participants
		-78.47 (349.15)
Week 95	Number Analyzed	16 participants
		-132.75 (301.36)
Week 99	Number Analyzed	18 participants
		-13.83 (155.04)
Week 103	Number Analyzed	20 participants
		-106.40 (309.44)
Week 107	Number Analyzed	20 participants
		-85.45 (312.50)
Week 111	Number Analyzed	19 participants
		-107.58 (286.18)
Week 115	Number Analyzed	19 participants
		-107.84 (293.61)
Week 119	Number Analyzed	19 participants
		-63.68 (310.56)
Week 123	Number Analyzed	20 participants
		-58.90 (339.49)
Week 127	Number Analyzed	18 participants
		-57.72 (400.26)
Week 131	Number Analyzed	19 participants
		-113.63 (344.53)
Week 135	Number Analyzed	17 participants
		-97.06 (339.41)
Week 139	Number Analyzed	13 participants
		-1.00 (256.65)
Week 143	Number Analyzed	10 participants
		180.70 (318.62)
Week 147	Number Analyzed	7 participants
		-10.29 (196.90)
Week 151	Number Analyzed	8 participants
		-24.13 (146.79)
Week 155	Number Analyzed	8 participants
		-17.38 (146.80)
Week 159	Number Analyzed	4 participants
		-126.00 (150.38)
Week 163	Number Analyzed	4 participants
		-31.50 (35.49)
Week 167	Number Analyzed	2 participants
		-48.50 (68.59)
Week 171	Number Analyzed	1 participants
		-23.00
Week 175	Number Analyzed	1 participants
		6.00
ET/SFU visit	Number Analyzed	20 participants
		-107.50 (249.28)

17. Secondary Outcome

Title	Part B: Number of Blood Transfusions Per Participant
Description	A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the participant had symptoms of anemia or Hgb was <7 g/dL and the participant was asymptomatic.
Time Frame	From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part-B FAS. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	22
Mean (Standard Deviation); Unit of Measure: blood transfusions per participant
	2.86 (6.58)

18. Secondary Outcome

Title	Part B: Number of Blood Units Transfused Per Participant
Description	A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the participant had symptoms of anemia or Hgb was <7 g/dL and the participant was asymptomatic.
Time Frame	From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS. Here, 'overall number of participants analyzed' = number of participants with at least 1 transfusion. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: blood units transfused per participants
	16.57 (16.85)

19. Secondary Outcome

Title	Part B: Change From Baseline in Haptoglobin Values at Each Specified Time Points
Description	Change in Haptoglobin values from baseline at each specified time points (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Haptoglobin values <0.2 were imputed as 0.2.
Time Frame	Baseline, Weeks 27,29,31,33,35,37,39,41,43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title		BIVV009
Arm/Group Description:		Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: grams per liter
Week 27	Number Analyzed	22 participants
		0.21 (0.38)
Week 29	Number Analyzed	21 participants
		0.21 (0.45)
Week 31	Number Analyzed	22 participants
		0.21 (0.43)
Week 33	Number Analyzed	22 participants
		0.28 (0.53)
Week 35	Number Analyzed	22 participants
		0.25 (0.41)
Week 37	Number Analyzed	21 participants
		0.14 (0.28)
Week 39	Number Analyzed	17 participants
		0.27 (0.49)
Week 41	Number Analyzed	20 participants
		0.39 (0.59)
Week 43	Number Analyzed	18 participants
		0.29 (0.47)
Week 45	Number Analyzed	21 participants
		0.16 (0.26)
Week 47	Number Analyzed	20 participants
		0.15 (0.35)
Week 49	Number Analyzed	21 participants
		0.21 (0.41)
Week 51	Number Analyzed	19 participants
		0.20 (0.37)
Week 53	Number Analyzed	22 participants
		0.23 (0.46)
Week 55	Number Analyzed	20 participants
		0.26 (0.45)
Week 57	Number Analyzed	20 participants
		0.26 (0.43)
Week 59	Number Analyzed	21 participants
		0.29 (0.44)
Week 61	Number Analyzed	21 participants
		0.23 (0.43)
Week 63	Number Analyzed	20 participants
		0.38 (0.50)
Week 65	Number Analyzed	20 participants
		0.25 (0.41)
Week 67	Number Analyzed	19 participants
		0.25 (0.42)
Week 69	Number Analyzed	20 participants
		0.24 (0.47)
Week 71	Number Analyzed	19 participants
		0.19 (0.33)
Week 73	Number Analyzed	19 participants
		0.13 (0.29)
Week 75	Number Analyzed	20 participants
		0.13 (0.24)
Week 77	Number Analyzed	21 participants
		0.17 (0.29)
Week 79	Number Analyzed	20 participants
		0.09 (0.22)
Week 83	Number Analyzed	20 participants
		0.14 (0.25)
Week 87	Number Analyzed	18 participants
		0.35 (0.53)
Week 91	Number Analyzed	19 participants
		0.17 (0.28)
Week 95	Number Analyzed	20 participants
		0.19 (0.33)
Week 99	Number Analyzed	18 participants
		0.21 (0.37)
Week 103	Number Analyzed	21 participants
		0.15 (0.25)
Week 107	Number Analyzed	21 participants
		0.26 (0.40)
Week 111	Number Analyzed	19 participants
		0.22 (0.33)
Week 115	Number Analyzed	18 participants
		0.21 (0.35)
Week 119	Number Analyzed	19 participants
		0.16 (0.31)
Week 123	Number Analyzed	20 participants
		0.19 (0.45)
Week 127	Number Analyzed	20 participants
		0.14 (0.23)
Week 131	Number Analyzed	19 participants
		0.18 (0.38)
Week 135	Number Analyzed	18 participants
		0.18 (0.35)
Week 139	Number Analyzed	13 participants
		0.10 (0.17)
Week 143	Number Analyzed	11 participants
		0.07 (0.16)
Week 147	Number Analyzed	8 participants
		0.06 (0.16)
Week 151	Number Analyzed	8 participants
		0.12 (0.24)
Week 155	Number Analyzed	8 participants
		0.09 (0.22)
Week 159	Number Analyzed	5 participants
		0.15 (0.34)
Week 163	Number Analyzed	4 participants
		0.30 (0.35)
Week 167	Number Analyzed	2 participants
		0.00 (0.00)
Week 171	Number Analyzed	1 participants
		0.00
Week 175	Number Analyzed	1 participants
		0.00
ET/SFU visit	Number Analyzed	20 participants
		0.02 (0.13)

20. Secondary Outcome

Title	Part B: Number of Healthcare Visits by Type
Description	In this outcome measure, number of healthcare visits which included non-study healthcare resource utilization visit (consisted mainly of extra visits to the office of the study doctor, or visit to a generalist doctor, or visit to a specialist doctor) and hospitalization visit and visit to hospital emergency is reported.
Time Frame	From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Part B-FAS. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).

Arm/Group Title	BIVV009
Arm/Group Description:	Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed	22
Measure Type: Number; Unit of Measure: visits
Non-study healthcare resource utilization visits	16
Hospitalization	8
Visit to a hospital emergency room	3

Adverse Events

Time Frame	Part A (both 6.5 g and 7.5 g cohorts): From first dose (Day 0) up to Week 26; Part B, 6.5 g cohort: From first dose (Week 27) up to 143 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 179). Part B, 7.5 g cohort: From first dose (Week 27) up to 149 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 185)
Adverse Event Reporting Description	Reported AEs and SAEs including fatal AEs were TEAEs that developed/worsened or became serious during on-treatment period. Analysis was performed on SAS.
Arm/Group Title	Part A: BIVV009 6.5 g		Part A: BIVV009 7.5 g		Part B: BIVV009 6.5 g		Part B: BIVV009 7.5 g
Arm/Group Description	Participants with primary CAD and body weight <75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25.		Participants with primary CAD and body weight >=75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25.		Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All participants who completed Part A elected to continue in Part B.		Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
All-Cause Mortality
	Part A: BIVV009 6.5 g		Part A: BIVV009 7.5 g		Part B: BIVV009 6.5 g		Part B: BIVV009 7.5 g
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/17 (0.00%)		1/7 (14.29%)		2/16 (12.50%)		0/6 (0.00%)
Serious Adverse Events
	Part A: BIVV009 6.5 g		Part A: BIVV009 7.5 g		Part B: BIVV009 6.5 g		Part B: BIVV009 7.5 g
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/17 (23.53%)		3/7 (42.86%)		10/16 (62.50%)		2/6 (33.33%)
Blood and lymphatic system disorders
Anaemia † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Cold Type Haemolytic Anaemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Haemolytic Anaemia † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Cardiac disorders
Angina Pectoris † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Coronary Artery Stenosis † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Stress Cardiomyopathy † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Eye disorders
Iridocyclitis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Retinal Detachment † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	2
Uveitis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Vitreous Haemorrhage † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	1/6 (16.67%)	1
Gastrointestinal disorders
Abdominal Pain Upper † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Gastrointestinal Haemorrhage † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Haemorrhoids † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Inguinal Hernia † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
General disorders
Inflammation † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Non-Cardiac Chest Pain † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Hepatobiliary disorders
Biliary Colic † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Cholecystitis Acute † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Cholelithiasis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Infections and infestations
Appendicitis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Asymptomatic Covid-19 † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Covid-19 Pneumonia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Erysipelas † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Escherichia Sepsis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Herpes Zoster † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Pneumococcal Sepsis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Pneumonia Klebsiella † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Respiratory Tract Infection † 1	1/17 (5.88%)	2	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Streptococcal Sepsis † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Urinary Tract Infection Bacterial † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	2	0/6 (0.00%)	0
Urosepsis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Viral Infection † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Wound Infection Staphylococcal † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Injury, poisoning and procedural complications
Femoral Neck Fracture † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic Cancer † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Meningioma † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Renal Cell Carcinoma † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Tubular Breast Carcinoma † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Nervous system disorders
Parkinsonism † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Transient Global Amnesia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Renal and urinary disorders
Urinary Retention † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Vascular disorders
Cyanosis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	3	0/6 (0.00%)	0
Peripheral Artery Thrombosis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Peripheral Vascular Disorder † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	2	0/6 (0.00%)	0
1 Term from vocabulary, MedDRA 24.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Part A: BIVV009 6.5 g		Part A: BIVV009 7.5 g		Part B: BIVV009 6.5 g		Part B: BIVV009 7.5 g
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/17 (88.24%)		6/7 (85.71%)		16/16 (100.00%)		6/6 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	0/17 (0.00%)	0	1/7 (14.29%)	3	5/16 (31.25%)	11	2/6 (33.33%)	2
Cold Type Haemolytic Anaemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	2	0/6 (0.00%)	0
Haemolysis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	1/6 (16.67%)	3
Haemolytic Anaemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Increased Tendency To Bruise † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Leukopenia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Monoclonal B-Cell Lymphocytosis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Thrombocytopenia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Cardiac disorders
Aortic Valve Incompetence † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Aortic Valve Sclerosis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Aortic Valve Stenosis † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Atrial Fibrillation † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Atrioventricular Block First Degree † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	2	0/6 (0.00%)	0
Cardiac Failure † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Coronary Artery Disease † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Mitral Valve Incompetence † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Sinus Bradycardia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Stress Cardiomyopathy † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Supraventricular Extrasystoles † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Tricuspid Valve Incompetence † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Ventricular Extrasystoles † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Ear and labyrinth disorders
Meniere's Disease † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	2
Tinnitus † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Vertigo † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Eye disorders
Cataract † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	2	0/6 (0.00%)	0
Dry Eye † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Macular Degeneration † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Ocular Discomfort † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Photopsia † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Visual Field Defect † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Visual Impairment † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Gastrointestinal disorders
Abdominal Distension † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Abdominal Pain † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	1/16 (6.25%)	1	0/6 (0.00%)	0
Abdominal Pain Upper † 1	1/17 (5.88%)	1	1/7 (14.29%)	1	2/16 (12.50%)	3	1/6 (16.67%)	8
Abdominal Tenderness † 1	1/17 (5.88%)	2	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Ascites † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Constipation † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	3/16 (18.75%)	3	1/6 (16.67%)	1
Dental Caries † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Diarrhoea † 1	1/17 (5.88%)	1	1/7 (14.29%)	1	2/16 (12.50%)	4	3/6 (50.00%)	4
Dyspepsia † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Dysphagia † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	2/16 (12.50%)	3	0/6 (0.00%)	0
Gastritis † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Gastritis Erosive † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Gastrooesophageal Reflux Disease † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Haemorrhoidal Haemorrhage † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Haemorrhoids † 1	2/17 (11.76%)	2	0/7 (0.00%)	0	1/16 (6.25%)	2	0/6 (0.00%)	0
Nausea † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	3/16 (18.75%)	3	2/6 (33.33%)	5
Oral Mucosal Blistering † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Periodontal Disease † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Stomatitis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Vomiting † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
General disorders
Asthenia † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	1/16 (6.25%)	4	1/6 (16.67%)	1
Catheter Site Haematoma † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Chest Discomfort † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Device Related Thrombosis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Drug Intolerance † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Facial Pain † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Fatigue † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	3/16 (18.75%)	3	3/6 (50.00%)	5
Feeling Cold † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Influenza Like Illness † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Malaise † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	1/6 (16.67%)	1
Mucosal Inflammation † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Non-Cardiac Chest Pain † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	1/6 (16.67%)	1
Oedema Peripheral † 1	1/17 (5.88%)	1	1/7 (14.29%)	1	2/16 (12.50%)	2	1/6 (16.67%)	2
Peripheral Swelling † 1	1/17 (5.88%)	2	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Pyrexia † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	3/16 (18.75%)	4	2/6 (33.33%)	4
Temperature Intolerance † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Hepatobiliary disorders
Biliary Colic † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Cholelithiasis † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Immune system disorders
Allergy To Arthropod Bite † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Autoinflammatory Disease † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Seasonal Allergy † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Infections and infestations
Abdominal Infection † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Asymptomatic Covid-19 † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Bacteriuria † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Bronchitis † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	1/6 (16.67%)	2
Cystitis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	7	1/6 (16.67%)	1
Cystitis Bacterial † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Escherichia Urinary Tract Infection † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	2	1/6 (16.67%)	2
Eye Infection † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Fungal Skin Infection † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Gastroenteritis † 1	2/17 (11.76%)	2	0/7 (0.00%)	0	1/16 (6.25%)	3	0/6 (0.00%)	0
Herpes Simplex Viraemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Infection † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Nasopharyngitis † 1	2/17 (11.76%)	2	0/7 (0.00%)	0	4/16 (25.00%)	6	0/6 (0.00%)	0
Oral Herpes † 1	1/17 (5.88%)	2	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Otitis Externa † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Otitis Externa Bacterial † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Pneumonia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Rash Pustular † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Respiratory Tract Infection Viral † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Root Canal Infection † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Skin Candida † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Skin Infection † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Tinea Pedis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	3	0/6 (0.00%)	0
Tooth Infection † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	2	0/6 (0.00%)	0
Upper Respiratory Tract Infection † 1	2/17 (11.76%)	4	0/7 (0.00%)	0	1/16 (6.25%)	1	1/6 (16.67%)	2
Urinary Tract Infection † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	3/16 (18.75%)	13	2/6 (33.33%)	6
Urinary Tract Infection Bacterial † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	1/6 (16.67%)	1
Viral Infection † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	1/16 (6.25%)	2	0/6 (0.00%)	0
Viral Upper Respiratory Tract Infection † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Injury, poisoning and procedural complications
Ankle Fracture † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Arthropod Bite † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Back Injury † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Bone Contusion † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Concussion † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Contusion † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	1/16 (6.25%)	1	0/6 (0.00%)	0
Exposure To Extreme Temperature † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Eye Contusion † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Fall † 1	1/17 (5.88%)	3	1/7 (14.29%)	1	1/16 (6.25%)	1	1/6 (16.67%)	1
Hand Fracture † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Infusion Related Reaction † 1	1/17 (5.88%)	1	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Joint Injury † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Limb Injury † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Procedural Pain † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Road Traffic Accident † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Skin Abrasion † 1	1/17 (5.88%)	2	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Spinal Column Injury † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Stress Fracture † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Tendon Rupture † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Investigations
Alanine Aminotransferase Increased † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Blood Creatinine Increased † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Blood Immunoglobulin G Decreased † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Blood Pressure Increased † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
C-Reactive Protein Increased † 1	0/17 (0.00%)	0	1/7 (14.29%)	1	0/16 (0.00%)	0	0/6 (0.00%)	0
Chest X-Ray Abnormal † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Computerised Tomogram Head Abnormal † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Serum Ferritin Decreased † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Weight Increased † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Metabolism and nutrition disorders
Cachexia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Decreased Appetite † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Gout † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Hypercholesterolaemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Hypertriglyceridaemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	2	0/6 (0.00%)	0
Hypoalbuminaemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Hypocalcaemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Hypokalaemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Hyponatraemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Hypophosphataemia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Iron Deficiency † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Magnesium Deficiency † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Malnutrition † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Vitamin B12 Deficiency † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	2/16 (12.50%)	2	2/6 (33.33%)	3
Back Pain † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	2
Coccydynia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Intervertebral Disc Calcification † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Muscle Spasms † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Myalgia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Neck Pain † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Osteoarthritis † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	2/16 (12.50%)	3	0/6 (0.00%)	0
Osteoporosis † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Pain In Extremity † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	3	0/6 (0.00%)	0
Rotator Cuff Syndrome † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Systemic Scleroderma † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Temporomandibular Joint Syndrome † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Tendonitis † 1	0/17 (0.00%)	0	1/7 (14.29%)	2	0/16 (0.00%)	0	1/6 (16.67%)	1
Trigger Finger † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma † 1	1/17 (5.88%)	1	1/7 (14.29%)	1	1/16 (6.25%)	1	0/6 (0.00%)	0
Bowen's Disease † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Myelodysplastic Syndrome † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Seborrhoeic Keratosis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Nervous system disorders
Brain Oedema † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Carotid Artery Stenosis † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Cerebrovascular Disorder † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Dizziness † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	3/16 (18.75%)	3	1/6 (16.67%)	1
Dizziness Postural † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	2	0/6 (0.00%)	0
Headache † 1	1/17 (5.88%)	1	1/7 (14.29%)	1	2/16 (12.50%)	2	2/6 (33.33%)	3
Multiple Sclerosis Relapse † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Paraesthesia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	2/16 (12.50%)	2	0/6 (0.00%)	0
Parkinsonism † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Seizure † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Syncope † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Psychiatric disorders
Adjustment Disorder † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Anxiety Disorder † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Confusional State † 1	1/17 (5.88%)	1	1/7 (14.29%)	1	1/16 (6.25%)	3	0/6 (0.00%)	0
Insomnia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Mental Fatigue † 1	1/17 (5.88%)	1	0/7 (0.00%)	0	0/16 (0.00%)	0	0/6 (0.00%)	0
Renal and urinary disorders
Acute Kidney Injury † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Chronic Kidney Disease † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Dysuria † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Haemoglobinuria † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Renal Failure † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	0/16 (0.00%)	0	1/6 (16.67%)	1
Renal Impairment † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Reproductive system and breast disorders
Benign Prostatic Hyperplasia † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0
Intermenstrual Bleeding † 1	0/17 (0.00%)	0	0/7 (0.00%)	0	1/16 (6.25%)	1	0/6 (0.00%)	0