Graves' Ophthalmopathy (GO)Phase 2NCT03938545
ASCEND GO-2: Study of RVT-1401 for the Treatment of Participants With Active, Moderate to Severe Graves' Ophthalmopathy ( GO )
A Phase 2 study testing RVT-1401 (Administered via subcutaneous injection) in people with Graves' Ophthalmopathy (GO), run by Immunovant Sciences GmbH at 25 sites in 5 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graves' Ophthalmopathy (GO)
- What is being tested?
- RVT-1401 (Administered via subcutaneous injection)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 25 sitesin 5 countries
- Study dates
- 23 Jul 2019to 15 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
25 sites in 5 countries.
25 sites in 5 countries
United States12 sites
University of Michigan - Kellogg Eye Center
Ann Arbor, Michigan, 48105
Multispecialty Aesthetic Clinical Research Organziation (MACRO)
Beverly Hills, California, 90212
Eye Wellness Center
Houston, Texas, 77005
University of Iowa Hospitals & Clinics - Eye Clinic
Iowa City, Iowa, 52242
University of Miami Miller School of Medicine Bascom Palmer Eye Institute
Miami, Florida, 33136
West Virginia University Eye Institute
Morgantown, West Virginia, 26506
Doheny Eye Center UCLA
Pasadena, California, 91105
Oregon Health & Science University (OHSU) - Casey Eye Institute (CEI)-Marquam Hill
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester Medical Center
Rochester, New York, 14642
Eyelid Center of Utah
Salt Lake City, Utah, 84102
Washington University School of Medicine - Center for Advanced Medicine (CAM) - Eye Center
St Louis, Missouri, 63146
Canada4 sites
Ophthalmology University Center- Hôpital Maisonneuve-Rosemont
Montreal, Quebec, H1T 2M4
Toronto Retina Institute
North York, Ontario, M3C 0G9
University of Ottawa Eye Institute
Ottawa, Ontario, K1H 8L6
University of British Columbia
Vancouver, British Columbia, V5Z-1M9
Germany3 sites
Universitat Duisburg-Essen
Duisburg, 47057
Orbitazentrum Frankfurt
Frankfurt am Main, 60318
Universitätsmedizin Mainz
Mainz, 55131
Italy3 sites
Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico
Milan, 20122
ARNAS Garibaldi, Presidio di Nesima
Palermo, Catania, 95122
Unità Operativa di Endocrinologia 2, Azienda Ospedaliero-Universitaria Pisana
Pisa, 56124
Spain3 sites
Centro de Oftalmologia Barraquer
Barcelona, 08021
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
University Hospital Ramon y Cajal
Madrid, 28034
About this study
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
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
- Conditions
- Graves' Ophthalmopathy (GO)
- Being tested
- RVT-1401 (Administered via subcutaneous injection), Placebo (Administered via subcutaneous injection)
- Keywords
- IMVT-1401, Graves' Orbitopathy, Thyroid Eye Disease
- Medical subject headings
- Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RVT-1401 (Administered via subcutaneous injection)Drug
RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody.
Placebo (Administered via subcutaneous injection)Other
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Regimen A-RVT-1401 | Experimental | Regimen A= RVT-1401 680 mg weekly for 12 weeks Receives: Drug: RVT-1401 (Administered via subcutaneous injection) |
| Regimen B-RVT-1401 | Experimental | Regimen B= RVT-1401 340 mg weekly for 12 weeks Receives: Drug: RVT-1401 (Administered via subcutaneous injection) |
| Regimen C-RVT-1401 | Experimental | Regimen C= RVT-1401 255 mg weekly for 12 weeks Receives: Drug: RVT-1401 (Administered via subcutaneous injection) |
| Placebo | Placebo comparator | for 12 weeks Receives: Other: Placebo (Administered via subcutaneous injection) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From Baseline up to Week 20
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Baseline and Week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2019
- Study start23 Jul 2019
- Primary completion2 Feb 2021
- Study completion15 Apr 2021
Why it stopped: Sponsor decision based on premature unblinding of treatment allocations necessitated by program-wide review
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graves' Ophthalmopathy (GO)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Immunovant Sciences GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03938545
- Sponsor's protocol ID
- RVT-1401-2001
- Status last verified
- Aug 2022
- First submitted
- 1 May 2019
- Last updated
- 22 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03938545
- Acronym / sponsor ID
- RVT-1401-2001
- Conditions
- Graves' Ophthalmopathy (GO)
- Keywords
- IMVT-1401, Graves' Orbitopathy, Thyroid Eye Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision based on premature unblinding of treatment allocations necessitated by program-wide review
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Immunovant Sciences GmbHIndustry (pharma, biotech, devices)
- Study start
- 23 Jul 2019 (actual)
- Primary completion
- 2 Feb 2021 (actual)
- Study completion
- 15 Apr 2021 (actual)
- First posted
- 6 May 2019 (actual)
- Results
- Posted 22 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Regimen A-RVT-1401 | Experimental | Drug: RVT-1401 (Administered via subcutaneous injection)Regimen A= RVT-1401 680 mg weekly for 12 weeks |
| Regimen B-RVT-1401 | Experimental | Drug: RVT-1401 (Administered via subcutaneous injection)Regimen B= RVT-1401 340 mg weekly for 12 weeks |
| Regimen C-RVT-1401 | Experimental | Drug: RVT-1401 (Administered via subcutaneous injection)Regimen C= RVT-1401 255 mg weekly for 12 weeks |
| Placebo | Placebo comparator | Other: Placebo (Administered via subcutaneous injection)for 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RVT-1401 (Administered via subcutaneous injection)RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody. | Drug | Regimen A-RVT-1401, Regimen B-RVT-1401, Regimen C-RVT-1401 |
| Placebo (Administered via subcutaneous injection)Placebo | Other | Placebo |
Primary outcome
Percentage of Participants With Proptosis Response at Week 13
Time frame: 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)
Time frame: 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.
3 secondary outcomes
Least Square Mean Percent Change From Baseline in Binding Anti-thyroid-stimulating Hormone Receptor (TSHR) Antibody Levels to Week 13
Time frame: Baseline and Week 13
Least Square Mean Percent Change From Baseline in Total IgG Levels
Time frame: Baseline and Week 13
Least Square Mean Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4
Time frame: Baseline and Week 13
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RVT-1401 (Administered via subcutaneous injection) in people with Graves' Ophthalmopathy (GO), run by Immunovant Sciences GmbH at 25 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Canada, Germany, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Proptosis Response at Week 13 (time frame: Baseline; Week 13). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2022.