A Study of RVT-1401 in Myasthenia Gravis (MG) Patients

NCT03863080 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RVT-1401-2002
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 20

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.

Conditions

Myasthenia Gravis

Keywords

IMVT-1401

Outcome Measures

Primary Outcomes (11)

• Double-Blind Treatment Period: 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 and which does not necessarily have to have a causal relationship with this treatment. SAEs were defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the other outcomes listed in the definition.

  Up to Week 18

• Open-Label Extension Period: Number of Participants Reporting AEs and SAEs

  An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. SAEs were defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the other outcomes listed in the definition.

  Up to Week 18

• Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Vital Signs

  Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate and temperature were measured after resting for at least 5 minutes in a semi-supine position.

  Up to Week 7

• Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs

  Vital signs including SBP, DBP, pulse rate and temperature were measured after resting for at least 5 minutes in a semi-supine position.

  Up to Week 18

• Double-blind Treatment Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters

  Clinical laboratory parameters included clinical chemistry, hematology and urinalysis.

  Up to Week 7

• Open-label Extension Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters

  Clinical laboratory parameters included clinical chemistry, hematology and urinalysis.

  Up to Week 18

• Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)

  Twelve-lead ECG was performed after 5 minutes of rest in the supine position.

  Up to Week 7

• Open-label Extension Period: Number of Participants With Clinically Significant Changes in ECG

  Twelve-lead ECG was performed after 5 minutes of rest in the supine position.

  Up to Week 18

• Double-blind Treatment Period: Percent Change From Baseline in Levels of Total Immunoglobulin G (IgG)

  Serum samples were collected for the analysis of total immunoglobulin G. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100.

  Baseline (Day 1) and Up to Week 7

• Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4

  Serum samples were collected for the analysis of IgG 1, 2, 3 and 4 levels. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100.

  Baseline (Day 1) and Up to Week 7

• Double-Blind Treatment Period: Percent Change From Baseline in Anti-acetylcholine Receptor Immunoglobulin G (Anti-AChR-IgG) at Week 7

  Serum samples were collected for the analysis of Anti-AChR-IgG. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100.

  Baseline (Day 1) and Week 7

Secondary Outcomes (15)

• Double-Blind Treatment Period: Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401

  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

• Open-label Extension Period: AUC0-168h of RVT-1401

  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

• Double-Blind Treatment Period: Maximum Concentration (Cmax) of RVT-1401

  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

• Open-label Extension Period: Cmax of RVT-1401

  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

• Double-Blind Treatment Period: Trough Concentrations (Ctrough) of RVT-1401

  Pre-dose

Study Arms (3)

Regimen A

EXPERIMENTAL

RVT-1401 680 mg weekly for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)

Drug: RVT-1401

Regimen B

EXPERIMENTAL

RVT-1401 340 mg weekly for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)

Drug: RVT-1401

Placebo

PLACEBO COMPARATOR

Placebo for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)

Drug: RVT-1401; Drug: Placebo

Interventions

RVT-1401 DRUG

Subcutaneous administration of RVT-1401

Placebo; Regimen A; Regimen B

Placebo DRUG

Subcutaneous administration of Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age.
• 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.
• QMG score ≥12 at Screening and Baseline.

You may not qualify if:

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

Sponsors & Collaborators

• Immunovant Sciences GmbH: lead

Study Sites (20)

IMC/Diagnostic and Medical Clinic

Mobile, Alabama, 36604, United States

Location

Phoenix Neurological Associates

Phoenix, Arizona, 85018, United States

Location

The Neurology Center of Southern California

Carlsbad, California, 92011, United States

Location

UC Irvine - MDA ALS and Neuromuscular Center

Orange, California, 92868, United States

Location

Care Access Research

Pasadena, California, 91101, United States

Location

CSNA

Colorado Springs, Colorado, 80907, United States

Location

Yale School of Medicine Department of Neurology

New Haven, Connecticut, 06510, United States

Location

Neurological Services of Orlando

Orlando, Florida, 32806, United States

Location

Rare Disease Research

Atlanta, Georgia, 30318, United States

Location

University of Minnesota - Department of Neurology

Minneapolis, Minnesota, 55455, United States

Location

Dent Institute

Amherst, New York, 14221, United States

Location

University of Buffalo

Buffalo, New York, 14260-1660, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Allegheny Neurological Associates

Pittsburgh, Pennsylvania, 15212, United States

Location

UTSW James W. Aston Ambulatory Care Center - Neurology Clinic

Dallas, Texas, 75390, United States

Location

University of Alberta Hospitals - Division of Pulmonary Medicine

Edmonton, Alberta, T6G 2G3, Canada

Location

London Health Sciences Centre

London, Ontario, N6G 2V4, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

University Health Network Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Central Study Contact
• Organization: Immunovant, Inc

clinicaltrials@immunovant.com

1-800-797-0414

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled Study with an Open-Label Extension

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: March 5, 2019
• Study Start: May 21, 2019
• Primary Completion: October 7, 2020
• Study Completion: December 21, 2020
• Last Updated: December 20, 2023
• Results First Posted: December 20, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5); US (15)