Back to resultsSafety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy
Primary Purpose
Immune Mediated Necrotizing Myopathy
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
zilucoplan
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Immune Mediated Necrotizing Myopathy
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of IMNM (Immune-Mediated Necrotizing Myopathy)
- Positive serology for anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) or anti-signal recognition particle (SRP) autoantibodies
- Clinical evidence of weakness (≤ grade 4 out of 5) on manual muscle testing in at least one proximal limb muscle group
- Creatine kinase (CK) of >1000 U/L at Screening
- No change in corticosteroid dose for at least 30 days prior to Baseline or anticipated to occur during the first 8-weeks on study
- No changes in immunosuppressive therapy, including dose, for at least 30 days prior to Baseline or anticipated to occur during the first 8-weeks on study
Exclusion Criteria:
- History of meningococcal disease
- Current or recent systemic infection within 2 weeks prior to Screening or infection requiring intravenous (IV) antibiotics within 4 weeks prior to Screening
- Recent initiation of intravenous immunoglobulin (IVIG) (i.e., first cycle administered less than 90 days prior to Baseline)
- Rituximab use within 90 days prior to Baseline or anticipated to occur during study
- Statin use within 30 days prior to Baseline or anticipated to occur during study
- Plasma exchange within 4 weeks prior to Baseline or expected to occur during the 8-week Treatment Period
Sites / Locations
- University of California Los Angeles
- University of California Irvine
- University of Florida Health Jacksonville
- University of South Florida
- University of Kansas Medical Center
- National Institute of Health
- Brigham and Women's Hospital
- Washington University School of Medicine in Saint Louis
- Northwell Health Neuroscience Institute
- The Ohio State University
- University of Pennsylvania
- Wesley Neurology Clinic
- Austin Neuromuscular Center
- The University of Texas Health Science Center at Houston
- Hôpital Universitaire Pitié Salpêtrière
- Amsterdam UMC
- University College London Hospitals NHS Foundation Trust
- Salford Royal NHS Barnes Clinical Research Facility
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
0.3 mg/kg zilucoplan
Placebo
Arm Description
Daily subcutaneous (SC) injection
Daily subcutaneous (SC) injection
Outcomes
Primary Outcome Measures
Percentage Change From Baseline to Week 8 in Serum Creatine Kinase (CK) Levels
All laboratory samples were obtained prior to administration of study drug at applicable visits. CK levels were measured by a central laboratory.
Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE)
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.
Secondary Outcome Measures
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
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.
Change From Baseline to Week 8 in Triple Timed Up and Go Test (3TUG) Time
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.
Change From Baseline to Week 8 in Proximal Manual Muscle Testing (MMT) Score
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.
Change From Baseline to Week 8 in Physician Global Activity Visual Analogue Scale (VAS) Score
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.
Change From Baseline to Week 8 in Patient Global Activity VAS Score
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.
Change From Baseline to Week 8 in HAQ Score
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.
Change From Baseline to Week 8 in MDAAT Extramuscular Disease Activity VAS Score
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.
Change From Baseline to Week 8 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04025632
Brief Title
Safety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy
Official Title
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated based on the primary efficacy endpoint analysis after the first data lock.
Study Start Date
November 7, 2019 (Actual)
Primary Completion Date
March 4, 2021 (Actual)
Study Completion Date
June 14, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ra Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of the study is to evaluate the safety and efficacy of zilucoplan in patients with Immune-Mediated Necrotizing Myopathy (IMNM). Subjects will be randomized in a 1:1 ratio to receive daily SC doses of 0.3 mg/kg zilucoplan or matching placebo for 8 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune Mediated Necrotizing Myopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
0.3 mg/kg zilucoplan
Arm Type
Experimental
Arm Description
Daily subcutaneous (SC) injection
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Daily subcutaneous (SC) injection
Intervention Type
Drug
Intervention Name(s)
zilucoplan
Intervention Description
Daily subcutaneous (SC) inection
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Daily subcutaneous (SC) inection
Primary Outcome Measure Information:
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)
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)
Secondary Outcome Measure Information:
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)
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)
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)
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)
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)
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)
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)
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of IMNM (Immune-Mediated Necrotizing Myopathy)
Positive serology for anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) or anti-signal recognition particle (SRP) autoantibodies
Clinical evidence of weakness (≤ grade 4 out of 5) on manual muscle testing in at least one proximal limb muscle group
Creatine kinase (CK) of >1000 U/L at Screening
No change in corticosteroid dose for at least 30 days prior to Baseline or anticipated to occur during the first 8-weeks on study
No changes in immunosuppressive therapy, including dose, for at least 30 days prior to Baseline or anticipated to occur during the first 8-weeks on study
Exclusion Criteria:
History of meningococcal disease
Current or recent systemic infection within 2 weeks prior to Screening or infection requiring intravenous (IV) antibiotics within 4 weeks prior to Screening
Recent initiation of intravenous immunoglobulin (IVIG) (i.e., first cycle administered less than 90 days prior to Baseline)
Rituximab use within 90 days prior to Baseline or anticipated to occur during study
Statin use within 30 days prior to Baseline or anticipated to occur during study
Plasma exchange within 4 weeks prior to Baseline or expected to occur during the 8-week Treatment Period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Cares
Organizational Affiliation
UCB Pharma
Official's Role
Study Director
Facility Information:
Facility Name
University of California Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of Florida Health Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
National Institute of Health
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Washington University School of Medicine in Saint Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Northwell Health Neuroscience Institute
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Wesley Neurology Clinic
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38018
Country
United States
Facility Name
Austin Neuromuscular Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78756
Country
United States
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hôpital Universitaire Pitié Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Amsterdam UMC
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
University College London Hospitals NHS Foundation Trust
City
London
ZIP/Postal Code
WC1N3BG
Country
United Kingdom
Facility Name
Salford Royal NHS Barnes Clinical Research Facility
City
Manchester
ZIP/Postal Code
M6 8HD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
IPD Sharing Time Frame
Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
IPD Sharing Access Criteria
Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
IPD Sharing URL
http://www.Vivli.org
Learn more about this trial
Safety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy
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