Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy (GO)

NCT03922321 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RVT-1401-1002
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study was to evaluate safety, tolerability, and pharmacodynamic parameters of RVT-1401 in graves' ophthalmopathy (GO) patients.

Conditions

Graves' Ophthalmopathy

Keywords

IMVT-1401; Graves' Orbitopathy; Thyroid Eye Disease

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Serious AE (SAE), Treatment-related Adverse Event (AE), and Death During the 6-week Treatment Period

  AEs were defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as AEs that either started on or after the date of the first dose of study drug and on or before the date of the last dose of study drug + 42 days, or had no recorded start date and the stop date was in between the date of the first dose and the last dose of study drug + 42 days. 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.

  from Baseline up to Week 6

• Number of Participants With Clinically Significant Findings Related to Vital Signs

  Clinical significance was determined by the investigator.

  up to Week 18

• Number of Participants With a Change From Normal Physical Examination Findings at Baseline to Abnormal Physical Examination Findings at the End of the Study

  Abnormality was determined by the investigator.

  up to Week 18

• Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs)

  Clinical significance was determined by the investigator.

  up to Week 18

• Percent Change From Baseline in Total Immunoglobulin G (IgG), IgG1, IgG2, IgG3, and IgG4 Levels

  The serum levels of total IgG and IgG subclasses (1-4) were determined. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7, Week 6 and 7 combined) minus the Baseline value, divided by the Baseline value x 100. A negative percent change from Baseline represents clinical improvement.

  Baseline; Week 7; Week 6 and 7 combined

• Mean Change From Baseline in Levels of Anti-thyroid-stimulating Hormone Receptor (Anti-TSHR) Antibodies at Week 7

  The serum levels of anti-TSHR antibodies were determined. Change from Baseline was calculated as the Week 7 value minus the Baseline value. A negative change from Baseline represents clinical improvement.

  Baseline; Week 7

Secondary Outcomes (6)

• Mean Change From Baseline in Proptosis in the Study Eye and Non-study Eye at Week 7

  Baseline; Week 7

• Number of Participants With an Overall Proptosis Response

  Up to Week 18

• 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

• 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

• Serum Concentration at the End of the Dosing Interval (Ctrough) of RVT-1401

  Week 2, Week 3, Week 4, Week 5, Week 6 Day 36, and Week 7

Study Arms (1)

RVT-1401

EXPERIMENTAL

RVT-1401 680 milligrams (mg) weekly for two weeks followed by 340 mg weekly for four weeks, administered subcutaneously

Drug: RVT-1401

Interventions

RVT-1401 DRUG

RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody.

RVT-1401

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.
• Clinical diagnosis of Graves' disease with hyperthyroidism associated with active, moderate to severe GO with a Clinical Activity Score (CAS) ≥ 4 for the most severely affected eye at Screening (on the 7-item scale) and Baseline (on the 10-item scale).
• Onset of active GO within 9 months of screening.
• Moderate-to-severe active GO (not sight-threatening but has an appreciable impact on daily life), usually associated with one or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, proptosis ≥ 3 mm above normal for race and gender, and/or inconstant or constant diplopia.

You may not qualify if:

• Use of any steroid (intravenous \[IV\] or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for the treatment of GO within 3 weeks prior to Screening.
• Use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months prior to Baseline.
• Total IgG level \< 6g/L at Screening.
• Absolute neutrophil count \<1500 cells/mm3 at Screening.
• Participants with decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months at Screening.
• Previous orbital irradiation or surgery for GO.

Sponsors & Collaborators

• Immunovant Sciences GmbH: lead

Study Sites (4)

UBC/VGH Eye Care Center

Vancouver, British Columbia, V5Z 3N9, Canada

Location

Toronto Retina Institute

North York, Ontario, M3C 0G9, Canada

Location

University of Ottwa Eye Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

CIUSSS de I'Est-de-I'lle-de-Montreal, Installation Maisonneuve- Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

MeSH Terms

Conditions

Graves Ophthalmopathy

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The PK parameters of AUC0-168h and Cmax were not estimated because of sparse PK sampling schedule.

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label study

Study Record Dates

• First Submitted: April 17, 2019
• First Posted: April 19, 2019
• Study Start: April 22, 2019
• Primary Completion: February 29, 2020
• Study Completion: May 21, 2020
• Last Updated: January 24, 2022
• Results First Posted: January 24, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)