Clinical trial NCT03863080: A Study of RVT-1401 in Myasthenia Gravis (MG) Patients
Official title: A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Extension of RVT-1401 in Myasthenia Gravis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthenia Gravis
Keywords: IMVT-1401
Lead sponsor: Immunovant Sciences GmbH
Sponsor class: INDUSTRY
First posted: 2019-03-05
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled Study with an Open-Label Extension
Primary purpose: TREATMENT

Brief summary: The purpose of the current study is to assess safety/tolerability and key pharmacodynamic (PD) effects that are considered to be associated with clinical benefit (reduction of total IgG and anti-AChR-IgG) in Myasthenia Gravis patients following treatment with RVT-1401 (also known as IMVT-1401) compared to placebo.


Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 18 years of age.
2. Myasthenia Gravis Foundation of America (MGFA) Class II-IVa and likely not in need of a respirator for the duration of the study as judged by the Investigator.
3. QMG score ≥12 at Screening and Baseline.

Other, more specific inclusion criteria are defined in the protocol.

Exclusion Criteria:

1. Use of rituximab, belimumab, eculizumab or any monoclonal antibody for immunomodulation within 6 months prior to first dosing.
2. Immunoglobulins given by SC, IV (IVIG), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 4 weeks before Screening.
3. Thymectomy performed \< 12 months prior to screening.
4. Total IgG level \<6 g/L (at screening).
5. Absolute neutrophil count \<1500 cells/mm3(at screening).

Other, more specific exclusion criteria are defined in the protocol

Primary outcomes:
measure: Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 18
measure: Open-Label Extension Period: Number of Participants Reporting AEs and SAEs
timeFrame: Up to Week 18
measure: Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Up to Week 7
measure: Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Up to Week 18
measure: Double-blind Treatment Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
timeFrame: Up to Week 7
measure: Open-label Extension Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
timeFrame: Up to Week 18
measure: Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
timeFrame: Up to Week 7
measure: Open-label Extension Period: Number of Participants With Clinically Significant Changes in ECG
timeFrame: Up to Week 18
measure: Double-blind Treatment Period: Percent Change From Baseline in Levels of Total Immunoglobulin G (IgG)
timeFrame: Baseline (Day 1) and Up to Week 7
measure: Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4
timeFrame: Baseline (Day 1) and Up to Week 7
measure: Double-Blind Treatment Period: Percent Change From Baseline in Anti-acetylcholine Receptor Immunoglobulin G (Anti-AChR-IgG) at Week 7
timeFrame: Baseline (Day 1) and Week 7
Secondary outcomes:
measure: Double-Blind Treatment Period: Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401
timeFrame: Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8
measure: Open-label Extension Period: AUC0-168h of RVT-1401
timeFrame: Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8, Week 9, Week 12 and Week 14
measure: Double-Blind Treatment Period: Maximum Concentration (Cmax) of RVT-1401
timeFrame: Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8
measure: Open-label Extension Period: Cmax of RVT-1401
timeFrame: Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8, Week 9, Week 12 and Week 14
measure: Double-Blind Treatment Period: Trough Concentrations (Ctrough) of RVT-1401
timeFrame: Pre-dose
measure: Open-label Extension Period: Ctrough of RVT-1401
timeFrame: Pre-dose
measure: Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score
timeFrame: Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36) and Week 7
measure: Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the QMG Score From Baseline
timeFrame: Baseline (Day 1) to Week 7
measure: Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score
timeFrame: Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36), Week 7
measure: Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the MG-ADL Score
timeFrame: Baseline (Day 1) to Week 7
measure: Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score
timeFrame: Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36), Week 7
measure: Double-Blind Treatment Period: Percentage of Participants With an Improvement on the MGC Score
timeFrame: Baseline (Day 1) to Week 7
measure: Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score
timeFrame: Baseline (Day 1) and at Week 4 and Week 7
measure: Double-Blind Treatment Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies
timeFrame: Up to Week 7
measure: Open-Label Extension Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies
timeFrame: Up to Week 18
Other outcomes:
Locations:
city: Mobile
country: United States
facility: IMC/Diagnostic and Medical Clinic
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Neurological Associates
state: Arizona
city: Carlsbad
country: United States
facility: The Neurology Center of Southern California
state: California
city: Orange
country: United States
facility: UC Irvine - MDA ALS and Neuromuscular Center
state: California
city: Pasadena
country: United States
facility: Care Access Research
state: California
city: Colorado Springs
country: United States
facility: CSNA
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine Department of Neurology
state: Connecticut
city: Orlando
country: United States
facility: Neurological Services of Orlando
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Minneapolis
country: United States
facility: University of Minnesota - Department of Neurology
state: Minnesota
city: Amherst
country: United States
facility: Dent Institute
state: New York
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: Pittsburgh
country: United States
facility: Allegheny Neurological Associates
state: Pennsylvania
city: Dallas
country: United States
facility: UTSW James W. Aston Ambulatory Care Center - Neurology Clinic
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta Hospitals - Division of Pulmonary Medicine
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: University Health Network Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
Study officials:
References: