Clinical trial NCT03938545: ASCEND GO-2: Study of RVT-1401 for the Treatment of Participants With Active, Moderate to Severe Graves' Ophthalmopathy ( GO )
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Graves' Ophthalmopathy (GO)
Keywords: IMVT-1401
Graves' Orbitopathy
Thyroid Eye Disease
Lead sponsor: Immunovant Sciences GmbH
Sponsor class: INDUSTRY
First posted: 2019-05-06
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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 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

Primary outcomes:
measure: Percentage of Participants With Proptosis Response at Week 13
timeFrame: Baseline; Week 13
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: From Baseline up to Week 20
Secondary outcomes:
measure: Least Square Mean Percent Change From Baseline in Binding Anti-thyroid-stimulating Hormone Receptor (TSHR) Antibody Levels to Week 13
timeFrame: Baseline and Week 13
measure: Least Square Mean Percent Change From Baseline in Total IgG Levels
timeFrame: Baseline and Week 13
measure: Least Square Mean Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4
timeFrame: Baseline and Week 13
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Multispecialty Aesthetic Clinical Research Organziation (MACRO)
state: California
city: Pasadena
country: United States
facility: Doheny Eye Center UCLA
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine Bascom Palmer Eye Institute
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics - Eye Clinic
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan - Kellogg Eye Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Center for Advanced Medicine (CAM) - Eye Center
state: Missouri
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU) - Casey Eye Institute (CEI)-Marquam Hill
state: Oregon
city: Houston
country: United States
facility: Eye Wellness Center
state: Texas
city: Salt Lake City
country: United States
facility: Eyelid Center of Utah
state: Utah
city: Morgantown
country: United States
facility: West Virginia University Eye Institute
state: West Virginia
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: North York
country: Canada
facility: Toronto Retina Institute
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Eye Institute
state: Ontario
city: Montreal
country: Canada
facility: Ophthalmology University Center- Hôpital Maisonneuve-Rosemont
state: Quebec
city: Duisburg
country: Germany
facility: Universitat Duisburg-Essen
city: Frankfurt am Main
country: Germany
facility: Orbitazentrum Frankfurt
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Palermo
country: Italy
facility: ARNAS Garibaldi, Presidio di Nesima
state: Catania
city: Milan
country: Italy
facility: Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico
city: Pisa
country: Italy
facility: Unità Operativa di Endocrinologia 2, Azienda Ospedaliero-Universitaria Pisana
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Centro de Oftalmologia Barraquer
city: Madrid
country: Spain
facility: University Hospital Ramon y Cajal
Study officials:
References: