Clinical trial NCT03922321: Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy (GO)
Official title: A Phase 2a, Multicenter, Open-Label Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graves' Ophthalmopathy
Keywords: IMVT-1401
Graves' Orbitopathy
Thyroid Eye Disease
Lead sponsor: Immunovant Sciences GmbH
Sponsor class: INDUSTRY
First posted: 2019-04-19
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label study
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 18 years of age.
2. 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).
3. Onset of active GO within 9 months of screening.
4. 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.
5. Other, more specific inclusion criteria are defined in the protocol

Exclusion Criteria:

1. 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.
2. Use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months prior to Baseline.
3. Total IgG level \< 6g/L at Screening.
4. Absolute neutrophil count \<1500 cells/mm3 at Screening.
5. 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.
6. Previous orbital irradiation or surgery for GO.
7. Other, more specific exclusion criteria are defined in the protocol

Primary outcomes:
measure: 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
timeFrame: from Baseline up to Week 6
measure: Number of Participants With Clinically Significant Findings Related to Vital Signs
timeFrame: up to Week 18
measure: Number of Participants With a Change From Normal Physical Examination Findings at Baseline to Abnormal Physical Examination Findings at the End of the Study
timeFrame: up to Week 18
measure: Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs)
timeFrame: up to Week 18
measure: Percent Change From Baseline in Total Immunoglobulin G (IgG), IgG1, IgG2, IgG3, and IgG4 Levels
timeFrame: Baseline; Week 7; Week 6 and 7 combined
measure: Mean Change From Baseline in Levels of Anti-thyroid-stimulating Hormone Receptor (Anti-TSHR) Antibodies at Week 7
timeFrame: Baseline; Week 7
Secondary outcomes:
measure: Mean Change From Baseline in Proptosis in the Study Eye and Non-study Eye at Week 7
timeFrame: Baseline; Week 7
measure: Number of Participants With an Overall Proptosis Response
timeFrame: Up to Week 18
measure: 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: 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: Serum Concentration at the End of the Dosing Interval (Ctrough) of RVT-1401
timeFrame: Week 2, Week 3, Week 4, Week 5, Week 6 Day 36, and Week 7
measure: Number of Participants With Anti-RVT-1401 Antibody and Confirmed Anti-RVT-1401 Antibody at Week 7
timeFrame: Week 7
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: UBC/VGH Eye Care Center
state: British Columbia
city: North York
country: Canada
facility: Toronto Retina Institute
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottwa Eye Institute
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de I'Est-de-I'lle-de-Montreal, Installation Maisonneuve- Rosemont
state: Quebec
Study officials:
References: