ASCEND GO-2: Study of RVT-1401 for the Treatment of Participants With Active, Moderate to Severe Graves' Ophthalmopathy ( GO )
- Conditions
- Graves' Ophthalmopathy (GO)
- Interventions
- Other: Placebo (Administered via subcutaneous injection)Drug: RVT-1401 (Administered via subcutaneous injection)
- Registration Number
- NCT03938545
- Lead Sponsor
- Immunovant Sciences GmbH
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 65
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo (Administered via subcutaneous injection) for 12 weeks Regimen A-RVT-1401 RVT-1401 (Administered via subcutaneous injection) Regimen A= RVT-1401 680 mg weekly for 12 weeks Regimen B-RVT-1401 RVT-1401 (Administered via subcutaneous injection) Regimen B= RVT-1401 340 mg weekly for 12 weeks Regimen C-RVT-1401 RVT-1401 (Administered via subcutaneous injection) Regimen C= RVT-1401 255 mg weekly for 12 weeks
- Primary Outcome Measures
Name Time Method Percentage of Participants With Proptosis Response at Week 13 Baseline; 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) From Baseline up to Week 20 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.
- Secondary Outcome Measures
Name Time Method Least Square Mean Percent Change From Baseline in Total IgG Levels Baseline and Week 13 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.
Least Square Mean Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 Baseline and Week 13 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.
Least Square Mean Percent Change From Baseline in Binding Anti-thyroid-stimulating Hormone Receptor (TSHR) Antibody Levels to Week 13 Baseline and 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.
Trial Locations
- Locations (25)
Universitat Duisburg-Essen
🇩🇪Duisburg, Germany
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
University of British Columbia
🇨🇦Vancouver, British Columbia, Canada
Hospital Universitari de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
University of Miami Miller School of Medicine Bascom Palmer Eye Institute
🇺🇸Miami, Florida, United States
Oregon Health & Science University (OHSU) - Casey Eye Institute (CEI)-Marquam Hill
🇺🇸Portland, Oregon, United States
Eyelid Center of Utah
🇺🇸Salt Lake City, Utah, United States
West Virginia University Eye Institute
🇺🇸Morgantown, West Virginia, United States
University of Michigan - Kellogg Eye Center
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Multispecialty Aesthetic Clinical Research Organziation (MACRO)
🇺🇸Beverly Hills, California, United States
Doheny Eye Center UCLA
🇺🇸Pasadena, California, United States
University of Iowa Hospitals & Clinics - Eye Clinic
🇺🇸Iowa City, Iowa, United States
Washington University School of Medicine - Center for Advanced Medicine (CAM) - Eye Center
🇺🇸Saint Louis, Missouri, United States
Eye Wellness Center
🇺🇸Houston, Texas, United States
Toronto Retina Institute
🇨🇦North York, Ontario, Canada
University of Ottawa Eye Institute
🇨🇦Ottawa, Ontario, Canada
Universitätsmedizin Mainz
🇩🇪Mainz, Germany
Ophthalmology University Center- Hôpital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
ARNAS Garibaldi, Presidio di Nesima
🇮🇹Palermo, Catania, Italy
Unità Operativa di Endocrinologia 2, Azienda Ospedaliero-Universitaria Pisana
🇮🇹Pisa, Italy
Centro de Oftalmologia Barraquer
🇪🇸Barcelona, Spain
Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
Orbitazentrum Frankfurt
🇩🇪Frankfurt am Main, Germany
University Hospital Ramon y Cajal
🇪🇸Madrid, Spain