Safety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy

• ClinicalTrials.gov Identifier: NCT04025632
• Recruitment Status: Terminated
• First Posted: July 19, 2019
• Results First Posted: May 16, 2022
• Last Update Posted: July 27, 2022
• Sponsor: Ra Pharmaceuticals
• Information provided by (Responsible Party): UCB Pharma ( Ra Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Immune Mediated Necrotizing Myopathy
• Interventions: Drug: zilucoplan; Other: Placebo
• Enrollment: 27

Participant Flow

Recruitment Details

This study was performed in 4 countries (France, the Netherlands, the United Kingdom, and the United States of America) between 07 November 2019 and 14 June 2021.

Pre-assignment Details

Of the 37 participants who were screened, 10 participants were deemed ineligible and were screen failures. 27 participants with immune-mediated necrotizing myopathy were randomized in a 1:1 ratio to receive zilucoplan 0.3 mg/kg or a matching placebo for the 8-week Treatment Period in the Main Portion of the study. All eligible participants were given the option to receive daily subcutaneous (SC) zilucoplan 0.3 mg/kg in the Extension Portion of the study.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Period Title: Overall Study
Started	15	12
Completed Main Portion	15	12
Started Main Portion Safety Follow-up [1]	2	0
Completed Main Portion Safety Follow-up [1]	0	0
Started Extension Portion	13	12
Completed [2]	0	0
Not Completed	15	12
Reason Not Completed
Adverse Event	1	1
Withdrawal by Subject	1	1
Study Terminated by Sponsor	10	9
Physician Decision	3	1
[1] Refers to study participants who completed the 8-week blinded treatment period in the Main Portion of the study and had not entered the Extension Portion.; [2] Completed Main Portion, Main Portion Safety Follow-up or Extension Portion.

Baseline Characteristics

Arm/Group Title		Placebo	Zilucoplan 0.3 mg/kg	Total
Arm/Group Description		Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Total of all reporting groups
Overall Number of Baseline Participants		15	12	27
Baseline Analysis Population Description		Intent-to-Treat (ITT) Population included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	15 participants	12 participants	27 participants
		52.8 (13.6)	56.9 (9.0)	54.6 (11.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants	12 participants	27 participants
	Female	7 46.7%	6 50.0%	13 48.1%
	Male	8 53.3%	6 50.0%	14 51.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants	12 participants	27 participants
	Hispanic or Latino	4 26.7%	5 41.7%	9 33.3%
	Not Hispanic or Latino	8 53.3%	5 41.7%	13 48.1%
	Unknown or Not Reported	3 20.0%	2 16.7%	5 18.5%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	15 participants	12 participants	27 participants
American Indian/Alaska native		0 0.0%	0 0.0%	0 0.0%
Asian		0 0.0%	0 0.0%	0 0.0%
Black or African American		1 6.7%	3 25.0%	4 14.8%
Native Hawaiian or other Pacific Islander		0 0.0%	0 0.0%	0 0.0%
White		10 66.7%	7 58.3%	17 63.0%
Other/Mixed		0 0.0%	0 0.0%	0 0.0%
Unknown or Not Reported		1 6.7%	0 0.0%	1 3.7%
Missing		3 20.0%	2 16.7%	5 18.5%

Outcome Measures

1. Primary Outcome

Title	Percentage Change From Baseline to Week 8 in Serum Creatine Kinase (CK) Levels
Description	All laboratory samples were obtained prior to administration of study drug at applicable visits. CK levels were measured by a central laboratory.
Time Frame	Baseline (Day 1) and end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The ITT Population with no missing observations at Baseline and Week 8.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Overall Number of Participants Analyzed	14	10
Mean (Standard Deviation); Unit of Measure: percentage change
	-20.72 (31.22)	-9.86 (26.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Zilucoplan 0.3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.464
	Comments	Conducted using a 2-sided Van Elteren test, which represents an extension of the Wilcoxon rank sum test for comparing 2 treatments in a stratified experiment using within-stratum ranks assigning greater weight to rank sums from smaller strata.
	Method	2-sided Van Elteren test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Wilcoxon-Mann-Whitney odds
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.19 to 1.57
	Estimation Comments	The magnitude of association between treatment groups was expressed as in Wilcoxon-Mann-Whitney odds followed by the 95% confidence intervals.

2. Primary Outcome

Title	Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE)
Description	A TEAE was defined as: An adverse event (AE) that occurred after study treatment start that was not present at the time of treatment start.; An AE that increased in severity after treatment start if the event was present at the time of treatment start.
Time Frame	Baseline (Day 1) to end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The Safety Population included all participants who have received at least 1 dose of study drug, with participants analyzed based on the actual study treatment received.

Arm/Group Title	Main Portion: Placebo	Main Portion: Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study.
Overall Number of Participants Analyzed	15	12
Measure Type: Count of Participants; Unit of Measure: Participants
	13 86.7%	9 75.0%

3. Secondary Outcome

Title	Number of Participants Who Achieve at Least Minimal Response Based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Response Criteria Scale
Description	The ACR/EULAR scale utilized a conjoint analysis-based continuous model using absolute percent change from Baseline in core set measures (physician, patient, and Myositis Disease Activity Assessment Tool (MDAAT); muscle strength; Health Assessment Questionnaire (HAQ); and muscle enzyme levels). A total improvement score (range 0-100) was determined by summing scores for each core set measure and comparing improvement in each respective core set measure. The threshold for minimal improvement was ≥20 in the total improvement score with higher scores indicating a better outcome.
Time Frame	Baseline (Day 1) and end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The ITT Population with no missing observations at Baseline and Week 8.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Overall Number of Participants Analyzed	14	11
Measure Type: Count of Participants; Unit of Measure: Participants
	7 50.0%	6 54.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Zilucoplan 0.3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.919
	Comments	P-value for the comparison of treatment groups was calculated using logistic regression with investigational medicinal product and strata as fixed factors.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.088
	Confidence Interval	(2-Sided) 95%; 0.214 to 5.535
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline to Week 8 in Triple Timed Up and Go Test (3TUG) Time
Description	The 3TUG test involved the ambulatory participant getting up from a seated position in a chair, walking at their normal pace for 3 meters, turning around, walking back to the chair, and sitting down. This sequence was repeated 3 times without rest, and the 3TUG test time is the average of the 3 lap times. A negative change from baseline indicated a better outcome.
Time Frame	Baseline (Day 1) and end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The ITT Population with no missing observations at Baseline and Week 8. The test was also only performed in participants who were ambulatory.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Overall Number of Participants Analyzed	10	10
Least Squares Mean (Standard Error); Unit of Measure: seconds
	-0.712 (0.789)	-1.401 (0.788)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Zilucoplan 0.3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.496
	Comments	Based on a linear model with treatment and strata (anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase [HMGCR]+/anti-signal recognition particle [SRP]+) as fixed factors with Baseline 3TUG as a covariate.
	Method	Linear Mixed Effect Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares (LS) mean difference
	Estimated Value	-0.688
	Confidence Interval	(2-Sided) 95%; -2.781 to 1.404
	Estimation Comments	The difference presented is zilucoplan 0.3 mg/kg minus placebo.

5. Secondary Outcome

Title	Change From Baseline to Week 8 in Proximal Manual Muscle Testing (MMT) Score
Description	The proximal MMT assessed muscle strength using manual muscle testing in 7 muscle groups (left and right sides assessed separately). The total MMT score for this study, inclusive of both sides, could range from 0-140, where 0 means no strength in any muscles and 140 means full strength in all the muscles examined. A negative change from Baseline indicated a worse outcome.
Time Frame	Baseline (Day 1) and end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The ITT Population with no missing observations at Baseline and Week 8.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Overall Number of Participants Analyzed	14	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.18 (3.44)	3.71 (3.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Zilucoplan 0.3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.431
	Comments	Based on a linear model with treatment and strata (anti-HMGCR+/anti-SRP+) as fixed factors with Baseline proximal MMT as a covariate.
	Method	Linear Mixed Effect Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	3.89
	Confidence Interval	(2-Sided) 95%; -6.18 to 13.95
	Estimation Comments	The difference presented is zilucoplan 0.3 mg/kg minus placebo.

6. Secondary Outcome

Title	Change From Baseline to Week 8 in Physician Global Activity Visual Analogue Scale (VAS) Score
Description	The Physician Global Activity VAS Score measured the treating physician's global evaluation of the participant's overall disease activity using a 10 cm VAS labelled with "no activity" at the left end and "maximum activity" at the right end. The Physician Global Activity VAS Score ranged from 0 (absent extramuscular disease activity) to 10 (maximum extramuscular disease activity). A negative change from Baseline indicated a better outcome.
Time Frame	Baseline (Day 1) and end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The ITT Population with no missing observations at Baseline and Week 8.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Overall Number of Participants Analyzed	15	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.626 (0.557)	-0.830 (0.671)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Zilucoplan 0.3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.800
	Comments	Based on a linear model with treatment and strata (anti-HMGCR+/anti-SRP+) as fixed factors with Baseline Physician Global Activity VAS as a covariate.
	Method	Linear Mixed Effect Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.204
	Confidence Interval	(2-Sided) 95%; -1.855 to 1.448
	Estimation Comments	The difference presented is zilucoplan 0.3 mg/kg minus placebo.

7. Secondary Outcome

Title	Change From Baseline to Week 8 in Patient Global Activity VAS Score
Description	The Patient Global Activity VAS Score measured the treating participant's global evaluation of their overall disease activity using a 10 cm VAS labelled with "no activity" at the left end and "maximum activity" at the right end. The Patient Global Activity VAS score ranged from 0 (absent extramuscular disease activity) to 10 (maximum extramuscular disease activity). A negative change from Baseline indicated a better outcome.
Time Frame	Baseline (Day 1) and end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The ITT Population with no missing observations at Baseline and Week 8.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Overall Number of Participants Analyzed	15	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.685 (0.707)	-1.966 (0.854)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Zilucoplan 0.3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.221
	Comments	Based on a linear model with treatment and strata (anti-HMGCR+/anti-SRP+) as fixed factors with Baseline Patient Global Activity VAS as a covariate.
	Method	Linear Mixed Effect Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-1.281
	Confidence Interval	(2-Sided) 95%; -3.390 to 0.829
	Estimation Comments	The difference presented is zilucoplan 0.3 mg/kg minus placebo.

8. Secondary Outcome

Title	Change From Baseline to Week 8 in HAQ Score
Description	The HAQ had 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities with 2 to 3 questions for each section. Scoring within each section ranged from 0 (without any difficulty) to 3 (unable to do). The total HAQ score was then calculated by summing the scores and dividing by the number of categories answered. The total HAQ score for this study could range from 0-3, where 0 means no functional impairment and 3 means complete functional impairment. A negative change from Baseline indicated a better outcome.
Time Frame	Baseline (Day 1) and end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The ITT Population with no missing observations at Baseline and Week 8.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Overall Number of Participants Analyzed	15	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	0.022 (0.151)	-0.125 (0.183)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Zilucoplan 0.3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.508
	Comments	Based on a linear model with treatment and strata (anti-HMGCR+/anti-SRP+) as fixed factors with Baseline HAQ as a covariate.
	Method	Linear Mixed Effect Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.147
	Confidence Interval	(2-Sided) 95%; -0.601 to 0.307
	Estimation Comments	The difference presented is zilucoplan 0.3 mg/kg minus placebo.

9. Secondary Outcome

Title	Change From Baseline to Week 8 in MDAAT Extramuscular Disease Activity VAS Score
Description	The MDAAT extramuscular disease activity VAS score measured the degree of disease activity of extramuscular organ systems and muscle. The scoring was performed by the physician and ranged from 0 (absent extramuscular disease activity) to 10 (maximum extramuscular disease activity). A negative change from Baseline indicated a better outcome.
Time Frame	Baseline (Day 1) and end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The ITT Population with no missing observations at Baseline and Week 8.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Overall Number of Participants Analyzed	15	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.144 (0.336)	-0.287 (0.398)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Zilucoplan 0.3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.765
	Comments	[Not Specified]
	Method	Linear Mixed Effect Model
	Comments	Based on a linear model with treatment and strata (anti-HMGCR+/anti-SRP+) as fixed factors with Baseline MDAAT as a covariate.
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.143
	Confidence Interval	(2-Sided) 95%; -1.123 to 0.837
	Estimation Comments	The difference presented is zilucoplan 0.3 mg/kg minus placebo.

10. Secondary Outcome

Title	Change From Baseline to Week 8 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score
Description	The FACIT-Fatigue Scale is a 13-item tool which measured an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue was measured on a 4-point Likert scale. The total FACIT-Fatigue Scale score for this study could range from 0-52, where 0 means the participants were very much fatigued during their usual daily activities and 52 means the participants were not at all fatigued during their usual daily activities. A negative change from Baseline indicated a worse outcome.
Time Frame	Baseline (Day 1) and end of Main Portion (Week 8)

Outcome Measure Data

Analysis Population Description

The ITT Population with no missing observations at Baseline and Week 8.

Arm/Group Title	Placebo	Zilucoplan 0.3 mg/kg
Arm/Group Description:	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.	Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study. All eligible participants were given the option to receive daily SC zilucoplan 0.3 mg/kg in the Extension Portion of the study.
Overall Number of Participants Analyzed	15	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	3.45 (3.41)	8.98 (4.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Zilucoplan 0.3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.265
	Comments	Based on a linear model with treatment and strata (anti-HMGCR+/anti-SRP+) as fixed factors with Baseline FACIT-Fatigue Scale as a covariate.
	Method	Linear Mixed Effect Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	5.53
	Confidence Interval	(2-Sided) 95%; -4.49 to 15.55
	Estimation Comments	The difference presented is zilucoplan 0.3 mg/kg minus placebo.

Adverse Events

Time Frame	Baseline (Day 1) to End of Safety Follow-up (Week 83)
Adverse Event Reporting Description	The Safety Population included all participants who have received at least 1 dose of study drug, with participants analyzed based on the actual study treatment received.
Arm/Group Title	Main Portion: Placebo		Main Portion: Zilucoplan 0.3 mg/kg		Extension Portion: Zilucoplan 0.3 mg/kg
Arm/Group Description	Participants were randomized to receive daily SC doses of matching placebo during the 8-week Main Portion of the study.		Participants were randomized to receive daily SC doses of zilucoplan 0.3 mg/kg during the 8-week Main Portion of the study.		Participants received daily SC doses of zilucoplan 0.3 mg/kg during the Extension Portion of the study.
All-Cause Mortality
	Main Portion: Placebo		Main Portion: Zilucoplan 0.3 mg/kg		Extension Portion: Zilucoplan 0.3 mg/kg
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/15 (0.00%)		0/12 (0.00%)		1/25 (4.00%)
Serious Adverse Events
	Main Portion: Placebo		Main Portion: Zilucoplan 0.3 mg/kg		Extension Portion: Zilucoplan 0.3 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/15 (20.00%)		0/12 (0.00%)		8/25 (32.00%)
Cardiac disorders
Ventricular tachycardia † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Gastrointestinal disorders
Rectal haemorrhage † 1	0/15 (0.00%)	0	0/12 (0.00%)	0	1/25 (4.00%)	1
General disorders
Asthenia † 1	0/15 (0.00%)	0	0/12 (0.00%)	0	1/25 (4.00%)	1
Infections and infestations
COVID-19 † 1	0/15 (0.00%)	0	0/12 (0.00%)	0	3/25 (12.00%)	4
Sinusitis bacterial † 1	0/15 (0.00%)	0	0/12 (0.00%)	0	1/25 (4.00%)	1
Staphylococcal sepsis † 1	0/15 (0.00%)	0	0/12 (0.00%)	0	1/25 (4.00%)	1
Rhinovirus infection † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Urinary tract infection † 1	1/15 (6.67%)	2	0/12 (0.00%)	0	0/25 (0.00%)	0
Investigations
Liver function test increased † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness † 1	0/15 (0.00%)	0	0/12 (0.00%)	0	1/25 (4.00%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
1 Term from vocabulary, MedDRA (24.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Main Portion: Placebo		Main Portion: Zilucoplan 0.3 mg/kg		Extension Portion: Zilucoplan 0.3 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/15 (86.67%)		9/12 (75.00%)		15/25 (60.00%)
Blood and lymphatic system disorders
Anaemia † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	2/25 (8.00%)	2
Cardiac disorders
Palpitations † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Sinus tachycardia † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Ear and labyrinth disorders
Vertigo † 1	2/15 (13.33%)	2	0/12 (0.00%)	0	1/25 (4.00%)	1
Gastrointestinal disorders
Nausea † 1	3/15 (20.00%)	3	3/12 (25.00%)	3	0/25 (0.00%)	0
Diarrhoea † 1	0/15 (0.00%)	0	0/12 (0.00%)	0	2/25 (8.00%)	2
Constipation † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	1/25 (4.00%)	1
Haemorrhoidal haemorrhage † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Faeces soft † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Lower gastrointestinal haemorrhage † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Vomiting † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
General disorders
Injection site pain † 1	1/15 (6.67%)	1	1/12 (8.33%)	1	1/25 (4.00%)	1
Injection site pruritus † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	1/25 (4.00%)	1
Influenza like illness † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	1/25 (4.00%)	1
Injection site erythema † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Oedema peripheral † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Fatigue † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Injection site bruising † 1	1/15 (6.67%)	2	0/12 (0.00%)	0	0/25 (0.00%)	0
Vaccination site pain † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Vessel puncture site bruise † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Infections and infestations
Sinusitis † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	1/25 (4.00%)	1
Conjunctivitis † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Nasopharyngitis † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	1/25 (4.00%)	1
Urinary tract infection pseudomonal † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Injury, poisoning and procedural complications
Fall † 1	0/15 (0.00%)	0	0/12 (0.00%)	0	3/25 (12.00%)	3
Contusion † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Skin procedural complication † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Investigations
Lipase increased † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	1/25 (4.00%)	1
Lymphocyte count decreased † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	1/25 (4.00%)	1
Amylase increased † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Weight decreased † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
White blood cell count decreased † 1	1/15 (6.67%)	1	1/12 (8.33%)	1	1/25 (4.00%)	1
Blood bilirubin increased † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Blood glucose increased † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Blood pressure increased † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Gamma-glutamyltransferase increased † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/15 (0.00%)	0	0/12 (0.00%)	0	2/25 (8.00%)	2
Myalgia † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	1/25 (4.00%)	1
Intervertebral disc protrusion † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Muscular weakness † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Neck pain † 1	0/15 (0.00%)	0	1/12 (8.33%)	1	0/25 (0.00%)	0
Tendonitis † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Nervous system disorders
Headache † 1	4/15 (26.67%)	5	4/12 (33.33%)	4	2/25 (8.00%)	2
Psychiatric disorders
Insomnia † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	1/25 (4.00%)	1
Renal and urinary disorders
Nephrolithiasis † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Skin and subcutaneous tissue disorders
Pruritus † 1	1/15 (6.67%)	1	1/12 (8.33%)	1	1/25 (4.00%)	1
Dermatitis contact † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	0/25 (0.00%)	0
Vascular disorders
Hypertension † 1	1/15 (6.67%)	1	0/12 (0.00%)	0	1/25 (4.00%)	1
1 Term from vocabulary, MedDRA (24.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

The study was terminated based on the primary efficacy endpoint analysis after the first data lock.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Clin Trial Reg & Results Disclosure
• Organization: UCB BIOSCIENCES GmbH
• Phone: Please email
• EMail: clinicaltrials@ucb.com

• Responsible Party: UCB Pharma ( Ra Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT04025632
• Other Study ID Numbers: RA101495-02.202
• First Submitted: July 17, 2019
• First Posted: July 19, 2019
• Results First Submitted: March 3, 2022
• Results First Posted: May 16, 2022
• Last Update Posted: July 27, 2022