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

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

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

Study Overview

• Status: Terminated
• Conditions: Graves' Ophthalmopathy (GO)
• Intervention / Treatment: Drug: RVT-1401 (Administered via subcutaneous injection); Other: Placebo (Administered via subcutaneous injection)

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z-1M9
      • University of British Columbia
  • Ontario
    • North York, Ontario, Canada, M3C 0G9
      • Toronto Retina Institute
    • Ottawa, Ontario, Canada, K1H 8L6
      • University of Ottawa Eye Institute
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Ophthalmology University Center- Hôpital Maisonneuve-Rosemont
• Germany
  • Duisburg, Germany, 47057
    • Universität Duisburg-Essen
  • Frankfurt am Main, Germany, 60318
    • Orbitazentrum Frankfurt
  • Mainz, Germany, 55131
    • Universitätsmedizin Mainz
• Italy
  • Milan, Italy, 20122
    • Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico
  • Pisa, Italy, 56124
    • Unità Operativa di Endocrinologia 2, Azienda Ospedaliero-Universitaria Pisana
  • Catania
    • Palermo, Catania, Italy, 95122
      • ARNAS Garibaldi, Presidio di Nesima
• Spain
  • Barcelona, Spain, 08021
    • Centro de Oftalmologia Barraquer
  • Madrid, Spain, 28034
    • University Hospital Ramón Y Cajal
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
• United States
  • California
    • Beverly Hills, California, United States, 90212
      • Multispecialty Aesthetic Clinical Research Organziation (MACRO)
    • Pasadena, California, United States, 91105
      • Doheny Eye Center UCLA
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine Bascom Palmer Eye Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics - Eye Clinic
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan - Kellogg Eye Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63146
      • Washington University School of Medicine - Center for Advanced Medicine (CAM) - Eye Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (OHSU) - Casey Eye Institute (CEI)-Marquam Hill
  • Texas
    • Houston, Texas, United States, 77005
      • Eye Wellness Center
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Eyelid Center of Utah
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female ≥18 years of age.
2. 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).
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 millimeters (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, 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.
2. Use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months prior to Baseline.
3. Total IgG level <6 grams per liter (g/L) at Screening.
4. Absolute neutrophil count <1500 cells per meter squared (cells/mm^3) 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Immunovant Sciences GmbH

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): February 2, 2021
• Study Completion (Actual): April 15, 2021

Study Registration Dates

• First Submitted: May 1, 2019
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (Actual): May 6, 2019

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: August 26, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: IMVT-1401; Graves' Orbitopathy; Thyroid Eye Disease
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Thyroid Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Eye Diseases; Graves Ophthalmopathy
• Other Study ID Numbers: RVT-1401-2001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No