ASCEND GO-2: Study of RVT-1401 for the Treatment of Participants With Active, Moderate to Severe Graves' Ophthalmopathy ( GO )

Study Overview
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Brief Summary
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The purpose of the current study is to assess the efficacy and safety/tolerability of three dose regimens of RVT-1401 in the treatment of active, moderate to severe GO participants. In addition, the study is designed to characterize the effect of RVT-1401 exposure on reduction in anti-TSHR IgG

Official Title
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ASCEND GO-2: A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled Study of RVT-1401 for the Treatment of Patients With Active, Moderate to Severe Graves' Ophthalmopathy

Conditions
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Graves' Ophthalmopathy (GO)

Intervention / Treatment
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* Drug: RVT-1401 (Administered via subcutaneous injection)
* Other: Placebo (Administered via subcutaneous injection)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 years of age. Clinical diagnosis of Graves' disease with hyperthyroidism associated with active, moderate to severe Graves' Ophthalmopathy (GO) with a Clinical Activity Score (CAS) ≥4 for the most severely affected eye at Screening and Baseline (on the 7-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 millimeters (mm), moderate or severe soft tissue involvement, proptosis ≥3 mm above normal for race and gender, and/or inconstant or constant diplopia. Other, more specific inclusion criteria are defined in the protocol Exclusion Criteria: Use of any steroid (intravenous, oral, steroid eye drops) for the treatment of GO or other conditions within 3 weeks prior to Screening. Steroids cannot be initiated during the trial. Exceptions include topical and inhaled steroids which are allowed. Use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months prior to Baseline. Total IgG level <6 grams per liter (g/L) at Screening. Absolute neutrophil count <1500 cells per meter squared (cells/mm^3) 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. Other, more specific exclusion criteria are defined in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A-RVT-1401<br>Regimen A= RVT-1401 680 mg weekly for 12 weeks | Drug: RVT-1401 (Administered via subcutaneous injection)<br>* RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody.<br>|
| Experimental: Regimen B-RVT-1401<br>Regimen B= RVT-1401 340 mg weekly for 12 weeks | Drug: RVT-1401 (Administered via subcutaneous injection)<br>* RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody.<br>|
| Experimental: Regimen C-RVT-1401<br>Regimen C= RVT-1401 255 mg weekly for 12 weeks | Drug: RVT-1401 (Administered via subcutaneous injection)<br>* RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody.<br>|
| Placebo Comparator: Placebo<br>for 12 weeks | Other: Placebo (Administered via subcutaneous injection)<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Proptosis Response at Week 13 | Proptosis was assessed using an exophthalmometer. A proptosis response was defined as having at least a 2 millimeter (mm) reduction in study eye proptosis without a deterioration (at least a 2 mm increase) in the fellow eye at the same visit. The study eye was defined as the most severely affected eye at the baseline visit. | Baseline; Week 13 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) | AEs - any untoward medical occurrences in a participant, temporally associated with use of a medicinal product, whether or not considered related to the product. Clinically significant changes determined by the Investigator such as vital signs, ECGs, and clinical laboratory values were also reported as AEs. TEAE is defined as an AE that starts on or after the first dose of the study drug and before 30 days after the last dose of the study drug. SAEs were defined as any untoward medical occurrences that: resulted in death; were life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; were congenital anomaly/birth defects; were important medical events that may have jeopardized the participant or may have required medical or surgical intervention; invasive or malignant cancers; and development of drug dependency or drug abuse. | From Baseline up to Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Least Square Mean Percent Change From Baseline in Binding Anti-thyroid-stimulating Hormone Receptor (TSHR) Antibody Levels to Week 13 | Binding Anti-TSHR antibody serum levels are directly associated with GO clinical features. Baseline was the last available assessment prior to the time of the first dose unless it was specified otherwise and was identified as Day 1. A negative change from baseline in binding anti-TSHR antibody levels indicated therapeutic benefit. | Baseline and Week 13 | 
| Least Square Mean Percent Change From Baseline in Total IgG Levels | Blood samples we collected to determine total IgG levels. Baseline was the last available assessment prior to the time of the first dose unless it was specified otherwise and was identified as Day 1. A negative change from baseline in the IgG levels indicated therapeutic benefit. | Baseline and Week 13 | 
| Least Square Mean Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | Blood samples were collected to determine IgG 1,2,3 and 4 levels. Baseline was the last available assessment prior to the time of the first dose unless it was specified otherwise and was identified as Day 1. A negative change from baseline in the IgG levels indicated therapeutic benefit. | Baseline and Week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IMVT-1401, Graves' Orbitopathy, Thyroid Eye Disease