Clinical trial NCT03315130: Safety and Efficacy Study of RA101495 in Subjects With Generalized Myasthenia Gravis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Generalized Myasthenia Gravis
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2017-10-19
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Main Portion: Change From Baseline to Week 12 in Quantitative Myasthenia Gravis (QMG) Score
timeFrame: From Baseline to Week 12
Secondary outcomes:
measure: Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Scale
timeFrame: From Baseline to Week 12
measure: Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Quality of Life 15r (MG-QOL15r) Survey
timeFrame: From Baseline to Week 12
measure: Main Portion: Change From Baseline to Week 12 in the MG Composite Scale Total Score
timeFrame: From Baseline to Week 12
measure: Main Portion: Percentage of Participants With >= 3-point Reduction in QMG Total Score at Week 12
timeFrame: Week 12
measure: Main Portion: Percentage of Participants Who Required Rescue Therapy Over the 12-week Treatment Period
timeFrame: Up to Week 12
measure: Main Portion: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Baseline to Week 12
measure: Main Portion: Change From Baseline in Sheep Red Blood Cell (sRBC) Lysis Assay at Week 12 (Pre-dose)
timeFrame: Baseline and Week 12 (Pre-dose)
measure: Main Portion: Change From Baseline in C5 Levels at Week 12 (Pre-dose)
timeFrame: Baseline and Week 12 (Pre-dose)
measure: Main Portion: Plasma Concentration of RA101495 and Its Major Metabolites
timeFrame: 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12
measure: Main Portion: Maximum Plasma Concentration (Cmax) on Day 1
timeFrame: Pre-dose, 1, 3 and 6 hours postdose on Day 1
measure: Main Portion: Time Corresponding to Cmax (Tmax) on Day 1
timeFrame: Pre-dose, 1, 3 and 6 hours postdose on Day 1
measure: Main Portion: Metabolites (RA102758 and RA103488) to Parent Ratio
timeFrame: Pre-dose, 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Diagnostic and Medical Clinic - Mobile
state: Alabama
city: Carlsbad
country: United States
facility: The Research Center of Southern California
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine Health ALS and Neuromuscular Center
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Buffalo
country: United States
facility: University of Buffalo
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Neurological Associates
state: Pennsylvania
city: Cordova
country: United States
facility: Wesley Neurology Clinic
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Milwaukee
country: United States
facility: Center for Neurological Disorders
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre University Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: 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, Henegar R, Bromberg M, Gibson S, Janecki T, Freimer M, Elsheikh B, Matisak P, Genge A, Guidon A, David W, Habib AA, Mathew V, Mozaffar T, Hinton JL, Hewitt W, Barnett D, Sullivan P, Ho D, Howard JF Jr, Traub RE, Chopra M, Kaminski HJ, Aly R, Bayat E, Abu-Rub M, Khan S, Lange D, Holzberg S, Khatri B, Lindman E, Olapo T, Sershon LM, Lisak RP, Bernitsas E, Jia K, Malik R, Lewis-Collins TD, Nicolle M, Nowak RJ, Sharma A, Roy B, Nye J, Pulley M, Berger A, Shabbir Y, Sachdev A, Patterson K, Siddiqi Z, Sivak M, Bratton J, Small G, Kohli A, Fetter M, Vu T, Lam L, Harvey B, Wolfe GI, Silvestri N, Patrick K, Zakalik K, Duda PW, MacDougall J, Farzaneh-Far R, Pontius A, Hoarty M. Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial. JAMA Neurol. 2020 May 1;77(5):582-592. doi: 10.1001/jamaneurol.2019.5125.