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 Description

Brief Summary:

The purpose of Part A was to determine whether sutimlimab administration resulted in a greater than or equal to (>=) 2 grams per deciliter (g/dL) increase in hemoglobin (Hgb) levels or increased Hgb to >= 12 g/dL and obviated the need for blood transfusion during treatment in participants with primary cold agglutinin disease (CAD) who had a recent history of blood transfusion. The purpose of Part B was to evaluate the long-term safety and tolerability of sutimlimab in participants with CAD.

Condition or disease	Intervention/treatment	Phase
Agglutinin Disease, Cold	Drug: BIVV009	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Pivotal, Open-label, Multicenter Study to Assess the Efficacy and Safety of Sutimlimab in Patients With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion
• Actual Study Start Date: March 5, 2018
• Actual Primary Completion Date: October 5, 2021
• Actual Study Completion Date: October 5, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: BIVV009; Participants with primary CAD who had a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an intravenous (IV) infusion of BIVV009 6.5 grams (g) (if body weight was less than [<] 75 kilograms [kg]) or BIVV009 7.5 g (if body weight was greater than or equal to [>=] 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.

Drug: BIVV009; Sutimlimab was administered as intravenous (IV) infusion.; Other Name: Sutimlimab

Outcome Measures

Primary Outcome Measures :

1. Part A: Percentage of Participants With Response to Treatment [ Time Frame: From Week 5 through Week 26 ]
   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).
2. Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [ 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) ]
   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).

Secondary Outcome Measures :

1. Part A: Mean Change From Baseline in Bilirubin Levels at the Treatment Assessment Timepoint [ Time Frame: Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26) ]
   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.
2. Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Treatment Assessment Timepoint [ Time Frame: Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26) ]
   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.
3. Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint [ Time Frame: Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26) ]
   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.
4. Part A: Number of Blood Transfusions Per Participant [ Time Frame: From Week 5 up to Week 26 ]
   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.
5. Part A: Number of Blood Units Transfused Per Participant [ Time Frame: From Week 5 up to Week 26 ]
   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.
6. Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint [ Time Frame: Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26) ]
   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.
7. Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points [ 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) ]
   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).
8. Part B: Change From Baseline in Bilirubin Levels at Each Specified Time Points [ 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) ]
   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).
9. 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 [ 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) ]
   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).
10. 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 [ Time Frame: Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135 and ET Visit/SFU visit (i.e., up to Week 185) ]
    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.
11. 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 [ 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) ]
    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).
12. 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 [ 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) ]
    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).
13. 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 [ 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) ]
    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).
14. Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points [ 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) ]
    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).
15. Part B: Number of Blood Transfusions Per Participant [ Time Frame: From Week 27 up to 149 weeks of treatment (i.e., up to Week 176) ]
    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.
16. Part B: Number of Blood Units Transfused Per Participant [ Time Frame: From Week 27 up to 149 weeks of treatment (i.e., up to Week 176) ]
    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.
17. Part B: Change From Baseline in Haptoglobin Values at Each Specified Time Points [ 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) ]
    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.
18. Part B: Number of Healthcare Visits by Type [ Time Frame: From Week 27 up to 149 weeks of treatment (i.e., up to Week 176) ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Body weight of >= 39 kg at screening.
• Confirmed diagnosis of primary CAD based on the following criteria: a) Chronic hemolysis; b) Polyspecific direct antiglobulin test (DAT) positive; c) Monospecific DAT strongly positive for C3d; d) Cold agglutinin titer >= 64 at 4 degree celsius; e) Immunoglobulin G (IgG) DAT less than or equal to (<=) 1+, and f) No overt malignant disease.
• History of at least one documented blood transfusion within 6 months of enrollment.
• Hemoglobin level <= 10.0 g/dL.
• Bilirubin level above the normal reference range, including participants with Gilbert's Syndrome.

Exclusion Criteria:

• Cold agglutinin syndrome secondary to infection, rheumatologic disease, or active hematologic malignancy.
• Clinically relevant infection of any kind within the month preceding enrollment (e.g., active hepatitis C, pneumonia).
• Clinical diagnosis of systemic lupus erythematosus; or other autoimmune disorders with anti-nuclear antibodies at Screening. Anti-nuclear antibodies of long-standing duration without associated clinical symptoms adjudicated on a case-by-case basis during the Confirmatory Review of Patient Eligibility.
• Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening.
• Positive human immunodeficiency virus (HIV) antibody at screening.
• Treatment with rituximab monotherapy within 3 months or rituximab combination therapies (e.g., with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment.

Contacts and Locations

Locations

United States, Arizona

Arizona Oncology Associates PC

Tucson, Arizona, United States, 85711

United States, California

USC/Keck School of Medicine

Los Angeles, California, United States, 90033

The Oncology Institute of Hope and Innovation

Whittier, California, United States, 90603

United States, District of Columbia

Georgetown University Medical Center

Georgetown, District of Columbia, United States, 20007

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, New York

Montefiore Medical Center

New York, New York, United States, 10461

New York Medical College at Westchester Medical Center

Valhalla, New York, United States, 10595

United States, North Carolina

East Carolina University

Greenville, North Carolina, United States, 27834

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15232

United States, Wisconsin

UW Hospitals and Clinics

Madison, Wisconsin, United States, 53792

Australia, Queensland

USC Health Clinics

Buderim, Queensland, Australia, 4556

Australia, Victoria

Ballarat Oncology & Haematology

Ballarat, Victoria, Australia, 3350

Monash Medical Centre

Clayton, Victoria, Australia, 3168

Austria

Medical University of Vienna

Vienna, Austria, 1090

Belgium

ZNA Stuivenberg

Antwerpen, Belgium, 2060

Centre Hospitalier Jolimont

La Louvière, Belgium, 7100

University Hospitals Leuven

Leuven, Belgium, 3000

Canada, Ontario

St. Michael's Hospital

Toronto, Ontario, Canada, M5B1W8

Canada, Quebec

McGill University Health Center

Montréal, Quebec, Canada, H4A3J1

Canada

University of Alberta

Edmonton, Canada, T6G1Z1

France

CHU de Caen

Caen, France, 14033

Centre Hospitalier Henri Mondor

Créteil, France, 94000

Centre Hospitalier Lyon Sud

Lyon, France, 69495

Germany

Gemeinschaftspraxis Hämatologie-Onkologie

Dresden, Germany, 1307

Universitätsklinikum Essen

Essen, Germany, 45147

Univ Ulm, Inst Klin. Transfusions. Immungen

Ulm, Germany, 89081

Israel

Hadassah Medical Center

Jerusalem, Israel, 91120

Laniado Hospital

Netanya, Israel, 4244916

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 64239

Italy

A. O. Spedali Civili di Brescia

Brescia, Italy, 25123

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy, 20122

U.O.C. Ematologia- Policlinico "A. Gemelli"

Rome, Italy, 00168

U.O.C. Ematologia Ospedale San Bortolo

Vicenza, Italy, 36100

Japan

Tokai University Hospital

Isehara, Kanagawa, Japan, 259-1193

Saitama Medical University Hospital

Iruma-gun, Saitama-Ken, Japan, 350-0495

Juntendo University Nerima Hospital

Tokyo, Tokyo-To, Japan, 177-8521

Netherlands

Academisch Medisch Centrum

Amsterdam, Netherlands, 1105

Norway

Haukeland University Hospital

Bergen, Norway, 5053

Oslo University Hospital

Oslo, Norway, 0372

St Olavs Hospital, Avdeling for blodsykdommer

Trondheim, Norway, 7030

Spain

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain, 28222

Hospital Clinci i Provincial de Barcelona

Barcelona, Spain, 08036

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

Hospital Universitario Dr. Peset

Valencia, Spain, 46017

United Kingdom

St James Hospital, Leeds

Leeds, United Kingdom, LS9 7TF

University College London

London, United Kingdom, WC1E 6AG

Sponsors and Collaborators

Bioverativ, a Sanofi company

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

  Study Documents (Full-Text)

Documents provided by Sanofi ( Bioverativ, a Sanofi company ):

Study Protocol  [PDF] December 19, 2019

Statistical Analysis Plan  [PDF] April 25, 2019

More Information

Additional Information:

Inhibition of Complement C1s with Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Results from the Phase 3 Cardinal Study 

Publications of Results:

Alexander Röth, Wilma Barcellini, Shirley D'Sa, Yoshitaka Miyakawa, Catherine M Broome, Marc Michel, David J. Kuter, Bernd Jilma, Tor Henrik Anderson Tvedt, Stella Lin, Xiaoyu Jiang, Caroline Reuter, William Hobbs, Sigbjørn Berentsen; Inhibition of Complement C1s with Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Results from the Phase 3 Cardinal Study. Blood 2019; 134 (Supplement_2): LBA-2. doi: https://doi.org/10.1182/blood-2019-132490

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Roth A, Barcellini W, Tvedt THA, Miyakawa Y, Kuter DJ, Su J, Jiang X, Hobbs W, Arias JM, Shafer F, Weitz IC. Sutimlimab improves quality of life in patients with cold agglutinin disease: results of patient-reported outcomes from the CARDINAL study. Ann Hematol. 2022 Oct;101(10):2169-2177. doi: 10.1007/s00277-022-04948-y. Epub 2022 Aug 23.

Tvedt THA, Steien E, Ovrebo B, Haaverstad R, Hobbs W, Wardecki M, Tjonnfjord GE, Berentsen SA. Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery. Am J Hematol. 2022 Feb 1;97(2):E51-E54. doi: 10.1002/ajh.26409. Epub 2021 Dec 11. No abstract available.

Roth A, Barcellini W, D'Sa S, Miyakawa Y, Broome CM, Michel M, Kuter DJ, Jilma B, Tvedt THA, Fruebis J, Jiang X, Lin S, Reuter C, Morales-Arias J, Hobbs W, Berentsen S. Sutimlimab in Cold Agglutinin Disease. N Engl J Med. 2021 Apr 8;384(14):1323-1334. doi: 10.1056/NEJMoa2027760.

• Responsible Party: Bioverativ, a Sanofi company
• ClinicalTrials.gov Identifier: NCT03347396
• Other Study ID Numbers: EFC16215; BIVV009-03 ( Other Identifier: Bioverativ Therapeutics Inc. ); 2017-003538-10 ( EudraCT Number )
• First Posted: November 20, 2017
• Results First Posted: October 31, 2022
• Last Update Posted: October 31, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Anemia, Hemolytic, Autoimmune; Anemia, Hemolytic; Anemia; Hematologic Diseases; Autoimmune Diseases; Immune System Diseases