Safety and Efficacy Study of RA101495 in Subjects With Generalized Myasthenia Gravis

Generalized Myasthenia Gravis Clinical Trial

Official title:

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of RA101495 in Subjects With Generalized Myasthenia Gravis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03315130
• Other study ID #: RA101495-02.201
• Status: Completed
• Phase: Phase 2
• Start date: October 11, 2017
• Est. completion date: November 19, 2020

Study information

• Verified date: July 2022
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: November 19, 2020
• Est. primary completion date: December 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis

Intervention

Drug:
• zilucoplan (RA101495)
Daily subcutaneous (SC) injection
• Placebo
Daily subcutaneous (SC) injection

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	London Health Sciences Centre University Hospital	London	Ontario
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
United States	University of Maryland	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Buffalo	Buffalo	New York
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Vermont	Burlington	Vermont
United States	The Research Center of Southern California	Carlsbad	California
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	Wesley Neurology Clinic	Cordova	Tennessee
United States	University of Texas Southwestern	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Michigan State University	East Lansing	Michigan
United States	University of Florida	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	UCLA Medical Center	Los Angeles	California
United States	Center for Neurological Disorders	Milwaukee	Wisconsin
United States	Diagnostic and Medical Clinic - Mobile	Mobile	Alabama
United States	Yale University	New Haven	Connecticut
United States	Hospital for Special Surgery	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	University of California Irvine Health ALS and Neuromuscular Center	Orange	California
United States	Allegheny Neurological Associates	Pittsburgh	Pennsylvania
United States	University of Utah	Salt Lake City	Utah
United States	University of South Florida	Tampa	Florida
United States	George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Ra Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Howard JF Jr, Nowak RJ, Wolfe GI, Freimer ML, Vu TH, Hinton JL, Benatar M, Duda PW, MacDougall JE, Farzaneh-Far R, Kaminski HJ; Zilucoplan MG Study Group, Barohn R, Dimachkie M, Pasnoor M, Farmakidis C, Liu T, Colgan S, Benatar MG, Bertorini T, Pillai R, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Main Portion: Change From Baseline to Week 12 in Quantitative Myasthenia Gravis (QMG) Score	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.	From Baseline to Week 12
Secondary	Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Scale	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.	From Baseline to Week 12
Secondary	Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Quality of Life 15r (MG-QOL15r) Survey	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.	From Baseline to Week 12
Secondary	Main Portion: Change From Baseline to Week 12 in the MG Composite Scale Total Score	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.	From Baseline to Week 12
Secondary	Main Portion: Percentage of Participants With >= 3-point Reduction in QMG Total Score at 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.	Week 12
Secondary	Main Portion: Percentage of Participants Who Required Rescue Therapy Over the 12-week Treatment Period	Percentage of participants who used at least 1 dose of rescue medication were reported.	Up to Week 12
Secondary	Main Portion: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	From Baseline to Week 12
Secondary	Main Portion: Change From Baseline in Sheep Red Blood Cell (sRBC) Lysis Assay at 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.	Baseline and Week 12 (Pre-dose)
Secondary	Main Portion: Change From Baseline in C5 Levels at Week 12 (Pre-dose)	Blood samples were collected from participants to assess Complement Component 5C levels.	Baseline and Week 12 (Pre-dose)
Secondary	Main Portion: Plasma Concentration of RA101495 and Its Major Metabolites	RA102758 and RA103488 are the metabolites of RA101495.	1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12
Secondary	Main Portion: Maximum Plasma Concentration (Cmax) on Day 1	Cmax is defined as the maximum observed plasma concentration.	Pre-dose, 1, 3 and 6 hours postdose on Day 1
Secondary	Main Portion: Time Corresponding to Cmax (Tmax) on Day 1	Tmax is defined as the time to observe maximum plasma concentration.	Pre-dose, 1, 3 and 6 hours postdose on Day 1
Secondary	Main Portion: Metabolites (RA102758 and RA103488) to Parent Ratio	RA102758 and RA103488 are the metabolites of RA101495.	Pre-dose, 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12