Safety and Efficacy Study of RA101495 in Subjects With Generalized Myasthenia Gravis
- Conditions
- Generalized Myasthenia Gravis
- Interventions
- Drug: Placebo
- Registration Number
- NCT03315130
- Lead Sponsor
- Ra Pharmaceuticals
- Brief Summary
The purpose of the study is to evaluate the safety and efficacy of RA101495 in patients with generalized Myasthenia Gravis (gMG). Subjects will be randomized in a 1:1:1 ratio to receive daily SC doses of 0.1 mg/kg RA101495, 0.3 mg/kg RA101495, or matching placebo for 12 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
- Diagnosis of gMG [Myasthenia Gravis Foundation of America (MGFA) Class II-IVa] at Screening
- Positive serology for acetylcholine receptor (AChR) autoantibodies
- QMG score ≥ 12 at Screening and Randomization
- No change in corticosteroid dose for at least 30 days prior to Randomization or anticipated to occur during the 12-week Treatment Period
- No change in immunosuppressive therapy, including dose, for at least 30 days prior to Randomization or anticipated to occur during the 12-week Treatment Period
- Thymectomy within 6 months prior to Randomization or scheduled to occur during the 12 week Treatment Period
- History of meningococcal disease
- Current or recent systemic infection within 2 weeks prior to Randomization or infection requiring intravenous (IV) antibiotics within 4 weeks prior to Randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.1 mg/kg zilucoplan (RA101495) zilucoplan (RA101495) - Placebo Placebo - 0.3 mg/kg zilucoplan (RA101495) zilucoplan (RA101495) -
- Primary Outcome Measures
Name Time Method Main Portion: Change From Baseline to Week 12 in Quantitative Myasthenia Gravis (QMG) Score From Baseline to Week 12 The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for myasthenia gravis (MG). The scale consists of 13 individual assessments, each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the individual scores with a range of 0-39. Higher scores are representative of more severe impairment.
- Secondary Outcome Measures
Name Time Method Main Portion: Change From Baseline in C5 Levels at Week 12 (Pre-dose) Baseline and Week 12 (Pre-dose) Blood samples were collected from participants to assess Complement Component 5C levels.
Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Scale From Baseline to Week 12 The MG-ADL is a brief 8-item survey designed to evaluate MG symptom severity. The scale consists of 8 items each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the 8 individual scores with range of 0-24. Higher scores are associated with more severe symptoms of MG.
Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Quality of Life 15r (MG-QOL15r) Survey From Baseline to Week 12 The MG-QOL15r is a 15-item survey that was designed to assess quality of life in participants with MG. The survey consisted of 15 questions and the corresponding responses were each scored on a 0-2 point scale (0=Not much at all, 1=Somewhat, 2=Very Much). The total score is the sum of the 15 individual item scores with a range of 0-30. Higher scores indicate more severe impact of the disease on aspects of the participant's life.
Main Portion: Change From Baseline in Sheep Red Blood Cell (sRBC) Lysis Assay at Week 12 (Pre-dose) Baseline and Week 12 (Pre-dose) A BioTek ELx800 automated microplate reader is used to measure the optical density at 415 nanometer (nm) of human plasma samples to calculate the percent lysis of sheep erythrocytes that has occurred as a result of total complement activity. The measure of complement activity is determined by the degree of hemolysis of the erythrocytes.
Main Portion: Change From Baseline to Week 12 in the MG Composite Scale Total Score From Baseline to Week 12 The MG Composite is a 10-item scale that has been used to measure the clinical status of participants with MG, in order to evaluate treatment response. It consists of 10 items which included ptosis (score range=0 to 3), double vision on lateral gaze left/right/both (score range=0 to 4), eye closure (score range=0 to 2), talking (score range=0 to 6), chewing (score range=0 to 6), swallowing (score range=0 to 6), breathing (score range=0 to 9), neck flexion or extension (score range=0 to 4), shoulder abduction (score range=0 to 5) and hip flexion (score range= 0 to 5). The total score is the sum of the 10 individual scores with a range of 0-50. Higher scores in the MG Composite indicate more severe impairment due to the disease.
Main Portion: Percentage of Participants With >= 3-point Reduction in QMG Total Score at Week 12 Week 12 The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consists of 13 individual assessments, each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the individual scores with a range of 0-39. Higher scores are representative of more severe impairment.
Main Portion: Percentage of Participants Who Required Rescue Therapy Over the 12-week Treatment Period Up to Week 12 Percentage of participants who used at least 1 dose of rescue medication were reported.
Main Portion: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Baseline to Week 12 An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulted in death, life-threatening, significant or persistent disability/incapacity, congenital anomaly/birth defect, important medical event, initial inpatient hospitalization or prolongation of hospitalization.
Main Portion: Plasma Concentration of RA101495 and Its Major Metabolites 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12 RA102758 and RA103488 are the metabolites of RA101495.
Main Portion: Maximum Plasma Concentration (Cmax) on Day 1 Pre-dose, 1, 3 and 6 hours postdose on Day 1 Cmax is defined as the maximum observed plasma concentration.
Main Portion: Time Corresponding to Cmax (Tmax) on Day 1 Pre-dose, 1, 3 and 6 hours postdose on Day 1 Tmax is defined as the time to observe maximum plasma concentration.
Main Portion: Metabolites (RA102758 and RA103488) to Parent Ratio Pre-dose, 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12 RA102758 and RA103488 are the metabolites of RA101495.
Trial Locations
- Locations (30)
University of Florida
🇺🇸Jacksonville, Florida, United States
Michigan State University
🇺🇸East Lansing, Michigan, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Wayne State University
🇺🇸Detroit, Michigan, United States
Wesley Neurology Clinic
🇺🇸Cordova, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Center for Neurological Disorders
🇺🇸Milwaukee, Wisconsin, United States
London Health Sciences Centre University Hospital
🇨🇦London, Ontario, Canada
Montreal Neurological Institute and Hospital
🇨🇦Montreal, Quebec, Canada
University of Vermont
🇺🇸Burlington, Vermont, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Diagnostic and Medical Clinic - Mobile
🇺🇸Mobile, Alabama, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
The Research Center of Southern California
🇺🇸Carlsbad, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
University of California Irvine Health ALS and Neuromuscular Center
🇺🇸Orange, California, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
George Washington University
🇺🇸Washington, District of Columbia, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
Lahey Hospital and Medical Center
🇺🇸Burlington, Massachusetts, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of Buffalo
🇺🇸Buffalo, New York, United States
Allegheny Neurological Associates
🇺🇸Pittsburgh, Pennsylvania, United States
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Yale University
🇺🇸New Haven, Connecticut, United States
University of South Florida
🇺🇸Tampa, Florida, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States