Back to resultsASCEND GO-2: Study of RVT-1401 for the Treatment of Participants With Active, Moderate to Severe Graves' Ophthalmopathy ( GO )
Primary Purpose
Graves' Ophthalmopathy (GO)
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RVT-1401 (Administered via subcutaneous injection)
Placebo (Administered via subcutaneous injection)
Sponsored by
About this trial
This is an interventional treatment trial for Graves' Ophthalmopathy (GO) focused on measuring IMVT-1401, Graves' Orbitopathy, Thyroid Eye Disease
Eligibility Criteria
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
Sites / Locations
- Multispecialty Aesthetic Clinical Research Organziation (MACRO)
- Doheny Eye Center UCLA
- University of Miami Miller School of Medicine Bascom Palmer Eye Institute
- University of Iowa Hospitals & Clinics - Eye Clinic
- University of Michigan - Kellogg Eye Center
- Mayo Clinic
- Washington University School of Medicine - Center for Advanced Medicine (CAM) - Eye Center
- University of Rochester Medical Center
- Oregon Health & Science University (OHSU) - Casey Eye Institute (CEI)-Marquam Hill
- Eye Wellness Center
- Eyelid Center of Utah
- West Virginia University Eye Institute
- University of British Columbia
- Toronto Retina Institute
- University of Ottawa Eye Institute
- Ophthalmology University Center- Hôpital Maisonneuve-Rosemont
- Universitat Duisburg-Essen
- Orbitazentrum Frankfurt
- Universitätsmedizin Mainz
- ARNAS Garibaldi, Presidio di Nesima
- Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico
- Unità Operativa di Endocrinologia 2, Azienda Ospedaliero-Universitaria Pisana
- Hospital Universitari de Bellvitge
- Centro de Oftalmologia Barraquer
- University Hospital Ramon y Cajal
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Regimen A-RVT-1401
Regimen B-RVT-1401
Regimen C-RVT-1401
Placebo
Arm Description
Regimen A= RVT-1401 680 mg weekly for 12 weeks
Regimen B= RVT-1401 340 mg weekly for 12 weeks
Regimen C= RVT-1401 255 mg weekly for 12 weeks
for 12 weeks
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03938545
Brief Title
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
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision based on premature unblinding of treatment allocations necessitated by program-wide review
Study Start Date
July 23, 2019 (Actual)
Primary Completion Date
February 2, 2021 (Actual)
Study Completion Date
April 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Immunovant Sciences GmbH
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graves' Ophthalmopathy (GO)
Keywords
IMVT-1401, Graves' Orbitopathy, Thyroid Eye Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Regimen A-RVT-1401
Arm Type
Experimental
Arm Description
Regimen A= RVT-1401 680 mg weekly for 12 weeks
Arm Title
Regimen B-RVT-1401
Arm Type
Experimental
Arm Description
Regimen B= RVT-1401 340 mg weekly for 12 weeks
Arm Title
Regimen C-RVT-1401
Arm Type
Experimental
Arm Description
Regimen C= RVT-1401 255 mg weekly for 12 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
for 12 weeks
Intervention Type
Drug
Intervention Name(s)
RVT-1401 (Administered via subcutaneous injection)
Intervention Description
RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody.
Intervention Type
Other
Intervention Name(s)
Placebo (Administered via subcutaneous injection)
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Percentage of Participants With Proptosis Response at Week 13
Description
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.
Time Frame
Baseline; Week 13
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)
Description
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.
Time Frame
From Baseline up to Week 20
Secondary Outcome Measure Information:
Title
Least Square Mean Percent Change From Baseline in Binding Anti-thyroid-stimulating Hormone Receptor (TSHR) Antibody Levels to Week 13
Description
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.
Time Frame
Baseline and Week 13
Title
Least Square Mean Percent Change From Baseline in Total IgG Levels
Description
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.
Time Frame
Baseline and Week 13
Title
Least Square Mean Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4
Description
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.
Time Frame
Baseline and Week 13
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Multispecialty Aesthetic Clinical Research Organziation (MACRO)
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90212
Country
United States
Facility Name
Doheny Eye Center UCLA
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
University of Miami Miller School of Medicine Bascom Palmer Eye Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Iowa Hospitals & Clinics - Eye Clinic
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Michigan - Kellogg Eye Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine - Center for Advanced Medicine (CAM) - Eye Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63146
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Oregon Health & Science University (OHSU) - Casey Eye Institute (CEI)-Marquam Hill
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Eye Wellness Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77005
Country
United States
Facility Name
Eyelid Center of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84102
Country
United States
Facility Name
West Virginia University Eye Institute
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z-1M9
Country
Canada
Facility Name
Toronto Retina Institute
City
North York
State/Province
Ontario
ZIP/Postal Code
M3C 0G9
Country
Canada
Facility Name
University of Ottawa Eye Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Ophthalmology University Center- Hôpital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Universitat Duisburg-Essen
City
Duisburg
ZIP/Postal Code
47057
Country
Germany
Facility Name
Orbitazentrum Frankfurt
City
Frankfurt am Main
ZIP/Postal Code
60318
Country
Germany
Facility Name
Universitätsmedizin Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
ARNAS Garibaldi, Presidio di Nesima
City
Palermo
State/Province
Catania
ZIP/Postal Code
95122
Country
Italy
Facility Name
Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico
City
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
Unità Operativa di Endocrinologia 2, Azienda Ospedaliero-Universitaria Pisana
City
Pisa
ZIP/Postal Code
56124
Country
Italy
Facility Name
Hospital Universitari de Bellvitge
City
Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Centro de Oftalmologia Barraquer
City
Barcelona
ZIP/Postal Code
08021
Country
Spain
Facility Name
University Hospital Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
ASCEND GO-2: Study of RVT-1401 for the Treatment of Participants With Active, Moderate to Severe Graves' Ophthalmopathy ( GO )
We'll reach out to this number within 24 hrs