An Efficacy, Safety, and Tolerability Study of VRDN-003 in Participants With Chronic Thyroid Eye Disease (TED)

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified August 2025 by Viridian Therapeutics, Inc.
Sponsor
Viridian Therapeutics, Inc.
Information Provided by (Responsible Party)
Viridian Therapeutics, Inc.
Clinicaltrials.gov Identifier
NCT06625398
Other Study ID Numbers:
VRDN-003-302
First Submitted
September 30, 2024
First Posted
October 2, 2024
Last Update Posted
September 29, 2025
Last Verified
August 2025

ClinicalTrials.gov processed this data on September 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

This is a randomized (meaning participants will be assigned to study arms by chance), double-masked (meaning study doctor and participant will not know which study arm participant is assigned to), placebo-controlled study that will include participants with chronic TED. The key objectives of this study are to determine if VRDN-003 is efficacious, safe and tolerable when administered as subcutaneous/SC injections every 4 weeks or every 8 weeks compared to placebo in participants with chronic TED.

Participants who do not have a meaningful response at Week 24 (irrespective of the initial treatment arm) may be eligible to receive additional subcutaneous injections of VRDN-003.

Condition or DiseaseIntervention/Treatment
Thyroid Eye Disease
Drug: VRDN-003Drug: VRDN-003Drug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment195 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleREVEAL-2 - A Phase 3, Randomized, Double-masked, Placebo-controlled, Efficacy, Safety, and Tolerability Study of VRDN-003 in Participants With Chronic Thyroid Eye Disease (TED)
Study Start DateAugust 26, 2024
Actual Primary Completion DateMarch 31, 2026
Actual Study Completion Date7mos 3d from now

Groups and Cohorts

Group/CohortIntervention/Treatment
VRDN-003 every 4 weeks
6 subcutaneous administrations of VRDN-003
Drug: VRDN-003
VRDN-003 is an investigational, subcutaneously administered, humanized monoclonal antibody directed against the Insulin-like Growth Factor-1 receptor (IGF-1R).
VRDN-003 every 8 weeks
3 subcutaneous administrations of VRDN-003 and 3 subcutaneous administrations of placebo
Drug: VRDN-003
VRDN-003 is an investigational, subcutaneously administered, humanized monoclonal antibody directed against the Insulin-like Growth Factor-1 receptor (IGF-1R).
Placebo every 4 weeks
6 subcutaneous administrations of placebo
Drug: Placebo
All participants will receive the same number of injections to maintain masking. Masking will be maintained by the use of placebo injections that appear identical to VRDN-003 injections.

Outcome Measures

Primary Outcome Measures
  1. Title: Proptosis Responder Rate in the study eye
    Description: Proportion of participants with a ≥2 mm reduction from baseline in proptosis in the study eye \[without a corresponding increase of ≥2 mm in the fellow eye\]
Secondary Outcome Measures
  1. Change from baseline in proptosis in the study eye
    Change from baseline in proptosis in the study eye
  2. Overall Responder Rate in the study eye
    Proportion of participants with a ≥2 mm reduction from baseline in proptosis in the study eye \[without a corresponding increase of ≥2 mm in the fellow eye\] AND no worsening in CAS from baseline in the study eye \[without a corresponding increase of ≥2 points in the fellow eye\]
  3. Diplopia Responder Rate for participants with baseline Diplopia Score greater than 0
    Proportion of participants with a reduction in Diplopia Score of ≥1 from baseline (for participants with baseline Diplopia Score greater than 0)
  4. Diplopia Resolution Rate for participants with baseline Diplopia Score greater than 0
    Proportion of participants with a reduction in Diplopia Score to 0 from baseline (for participants with baseline Diplopia Score greater than 0)

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Must have moderate to severe chronic TED, with any CAS (0-7) on the 7-item scale, and with documented evidence of ocular symptoms or signs that began greater than 15 months prior to screening
Must agree to use highly effective contraception as specified in the protocol
Female TED participants must have a negative serum pregnancy test at screening Key
Exclusion Criteria
Must not have received prior treatment with another anti-IGF-1R therapy
Must not have received systemic corticosteroids or steroid eye drops for any condition, including TED, or selenium within 2 weeks prior to first dose.
Must not have received other immunosuppressive drugs for any condition, including TED, or any other therapy for TED within 12 weeks prior to first dose
Must not have received an investigational agent for any condition, including TED, within 8 weeks or longer duration (depending on the type of investigational agent) prior to first dose
Must not have received radioactive iodine (RAI) treatment within 8 weeks prior to first dose
Must not have had previous orbital irradiation or decompression surgery for TED to the study eye's orbit
Must not have a pre-existing ophthalmic condition in the study eye which in the study doctor's opinion, would interfere with interpretation of study results
Must not have abnormal hearing test before first dose. Must also not have a history of ear conditions considered significant by study doctor
Must not have a history of inflammatory bowel disease
Female TED participants must not be pregnant or breastfeeding NOTE: There are additional eligibility criteria for participants who do not have a meaningful response at Week 24 (irrespective of initial treatment arm) who may receive additional injections of VRDN-003. These are described in the protocol.

Contacts and Locations

Sponsors and CollaboratorsViridian Therapeutics, Inc.
Locations
Scottsdale Clinical Trials | Scottsdale Arizona, United States, 85260Alliance Research Institute - Canoga Park | Canoga Park California, United States, 91304Marvel Clinical Research | Huntington Beach California, United States, 92647United Medical Research Institute | Inglewood California, United States, 90301Advancing Research International, LLC | Los Angeles California, United States, 90023Roski Eye Institute, Keck School of Medicine, USC | Los Angeles California, United States, 90033Alliance Research Institute - Lynwood | Lynwood California, United States, 90262A.P.J. Office | Newport Beach California, United States, 92660Byers Eye Institute at Stanford University | Palo Alto California, United States, 94303Pasadena Clinical Trials | Pasadena California, United States, 91101Senta Clinic | San Diego California, United States, 92108Ilumina Medical Research | Kissimmee Florida, United States, 34744Med-Care Research | Miami Florida, United States, 33125Hype Clinical Research LLC | Miami Florida, United States, 33145Anmed Health Services LLC | Miami Florida, United States, 33193Southern Clinical Research LLc | Miami Florida, United States, 33990Sarasota Retina Institute | Sarasota Florida, United States, 34239Agile Clinical Research Trials, LLC | Atlanta Georgia, United States, 30328Vision Medical Research | Orland Park Illinois, United States, 60462Massachusetts Eye and Ear | Boston Massachusetts, United States, 02114Opthalmic Consultants of Boston | East Weymouth Massachusetts, United States, 02189Fraser Eye Care Center | Fraser Michigan, United States, 48026Kahana Oculoplastic & Orbital Surgery | Livonia Michigan, United States, 48152University Health | Kansas City Missouri, United States, 64108S.L. Office | Las Vegas Nevada, United States, 89144Vector Clinical Trials | Sparks Nevada, United States, 89436Rutgers New Jersey Medical School | Newark New Jersey, United States, 07103Asheville Clinical Research | Asheville North Carolina, United States, 28803Duke Eye Center | Durham North Carolina, United States, 27710Scheie Eye Institute Penn Presbyterian | Philadelphia Pennsylvania, United States, 19104Wills Eye Hospital | Philadelphia Pennsylvania, United States, 19107Horizon Clinical Research Group | Cypress Texas, United States, 77429Baylor College of Medicine/Alkek Eye Center | Houston Texas, United States, 77030Gulf Coast Clinical Trials | Houston Texas, United States, 77070Neuro-Eye Clinical Trials | Houston Texas, United States, 77074University of Washington, Eye institute | Seattle Washington, United States, 98104West Virginia University Eye Institute | Morgantown West Virginia, United States, 26506