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Trial record 2 of 2 for:    02.202

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04025632
Recruitment Status : Terminated (The study was terminated based on the primary efficacy endpoint analysis after the first data lock.)
First Posted : July 19, 2019
Results First Posted : May 16, 2022
Last Update Posted : July 27, 2022
Sponsor:
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
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
Hide 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.
Arm/Group Title Placebo Zilucoplan 0.3 mg/kg Total
Hide 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
Hide 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%
1.Primary Outcome
Title Percentage Change From Baseline to Week 8 in Serum Creatine Kinase (CK) Levels
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population with no missing observations at Baseline and Week 8.
Arm/Group Title Placebo Zilucoplan 0.3 mg/kg
Hide 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)
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population with no missing observations at Baseline and Week 8.
Arm/Group Title Placebo Zilucoplan 0.3 mg/kg
Hide 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%
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population with no missing observations at Baseline and Week 8.
Arm/Group Title Placebo Zilucoplan 0.3 mg/kg
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population with no missing observations at Baseline and Week 8.
Arm/Group Title Placebo Zilucoplan 0.3 mg/kg
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population with no missing observations at Baseline and Week 8.
Arm/Group Title Placebo Zilucoplan 0.3 mg/kg
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population with no missing observations at Baseline and Week 8.
Arm/Group Title Placebo Zilucoplan 0.3 mg/kg
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population with no missing observations at Baseline and Week 8.
Arm/Group Title Placebo Zilucoplan 0.3 mg/kg
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population with no missing observations at Baseline and Week 8.
Arm/Group Title Placebo Zilucoplan 0.3 mg/kg
Hide 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)
Hide 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.
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
Hide 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%)    
Hide 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
Hide 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
The study was terminated based on the primary efficacy endpoint analysis after the first data lock.
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
Layout table for Results Point of Contact information
Name/Title: Clin Trial Reg & Results Disclosure
Organization: UCB BIOSCIENCES GmbH
Phone: Please email
EMail: clinicaltrials@ucb.com
Layout table for additonal information
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