An Efficacy, Safety, and Tolerability Study of VRDN-003 in Participants With Active Thyroid Eye Disease (TED) (REVEAL-1)

REVEAL-1 - A Phase 3, Randomized, Double-masked, Placebo-controlled, Efficacy, Safety, and Tolerability Study of VRDN-003 in Participants With Active Thyroid Eye Disease (TED)

This is a clinical trial assessing the efficacy, safety, and tolerability of an investigational drug, VRDN-003, in participants with active Thyroid Eye Disease (TED).

Study Overview

• Status: Active, not recruiting
• Conditions: Thyroid Eye Disease
• Intervention / Treatment: Drug: VRDN-003; Drug: Placebo

Detailed 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 active TED. The key objectives of this study are to determine if VRDN-003 is efficacious, safe and tolerable when administered as a series of subcutaneous/SC injections given every 4 weeks or every 8 weeks compared to placebo in participants with active 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.

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Scottsdale Clinical Trials
  • California
    • Canoga Park, California, United States, 91304
      • Alliance Research Institute - Canoga Park
    • Huntington Beach, California, United States, 92647
      • Marvel Clinical Research
    • Inglewood, California, United States, 90301
      • United Medical Research Institute
    • Los Angeles, California, United States, 90023
      • Advancing Research International, LLC
    • Los Angeles, California, United States, 90033
      • Roski Eye Institute, Keck School of Medicine, USC
    • Lynwood, California, United States, 90262
      • Alliance Research Institute - Lynwood
    • Newport Beach, California, United States, 92660
      • A.P.J. Office
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Stanford University
    • Pasadena, California, United States, 91101
      • Pasadena Clinical Trials
    • San Diego, California, United States, 92108
      • Senta Clinic
  • Florida
    • Cape Coral, Florida, United States, 33990
      • C&A Clinical Trials Corp
    • Kissimmee, Florida, United States, 34744
      • Ilumina Medical Research
    • Miami, Florida, United States, 33144
      • Continental Clinical Research
    • Miami, Florida, United States, 33125
      • Med-Care Research
    • Miami, Florida, United States, 33145
      • Hype Clinical Research LLC
    • Miami, Florida, United States, 33193
      • Anmed Health Services LLC
    • Sarasota, Florida, United States, 34239
      • Sarasota Retina Institute
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Agile Clinical Research Trials, LLC
  • Illinois
    • Orland Park, Illinois, United States, 60462
      • Vision Medical Research
  • Massachusetts
    • East Weymouth, Massachusetts, United States, 02189
      • Opthalmic Consultants of Boston
  • Michigan
    • Fraser, Michigan, United States, 48026
      • Fraser Eye Care Center
    • Livonia, Michigan, United States, 48152
      • Kahana Oculoplastic & Orbital Surgery
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • University Health
  • Nevada
    • Las Vegas, Nevada, United States, 89144
      • S.L. Office
    • Sparks, Nevada, United States, 89436
      • Vector Clinical Trials
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Clinical Research
    • Durham, North Carolina, United States, 27705
      • Duke Eye Center
  • Texas
    • Houston, Texas, United States, 77074
      • Neuro-Eye Clinical Trials
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/Alkek Eye Center
    • Houston, Texas, United States, 77070
      • Gulf Coast Clinical Trials
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington, Eye institute
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Must have moderate to severe active TED with documented evidence of ocular symptoms or signs that began within 15 months prior to screening
• Must have a Clinical Activity Score (CAS) of ≥ 3 on the 7-item scale for the study eye
• 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 who 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).
Experimental: 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).; 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.
Placebo Comparator: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proptosis Responder Rate in the most proptotic eye as measured by exophtalmometer	Proportion of participants with a ≥2 mm reduction from baseline in proptosis in the most proptotic eye as measured by exophtalmometer [without a corresponding increase of ≥2 mm in the other eye]	At Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	At Week 24
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)	At Week 24
Change from baseline in proptosis in the most proptotic eye as measured by exophthalmometer	Change from baseline in proptosis in the most proptotic eye as measured by exophthalmometer	At Week 24
Proptosis Responder Rate in the most proptotic eye as measured by MRI	Proportion of participants with a ≥2 mm reduction from baseline in proptosis in the most proptotic eye as measured by MRI [without a corresponding increase of ≥2 mm in the other eye]	At Week 24
Change from baseline in proptosis in the most proptotic eye as measured by MRI	Change from baseline in proptosis in the most proptotic eye as measured by MRI	At Week 24
Overall Responder Rate in the most proptotic eye as measured by exophthalmometer	Proportion of participants with a ≥2 mm reduction from baseline in proptosis in the most proptotic eye as measured by exophthalmometer [without a corresponding increase of ≥2 mm in the other eye] AND ≥ 2 points reduction in Clinical Activity Score (CAS) from baseline in the most proptotic eye as measured by exophthalmometer [without a corresponding increase of ≥2 points in the other eye]	At Week 24
Change from baseline in Clinical Activity Score (CAS) in the most proptotic eye (as measured by exophthalmometer)	Change from baseline in Clinical Activity Score (CAS) in the most proptotic eye (as measured by exophthalmometer) [range, 0 to 7, with higher scores indicating greater level of inflammation]	At Week 24
Proportion of participants with a Clinical Activity Score (CAS) of 0 or 1 in the most proptotic eye (as measured by exophthalmometer)	Proportion of participants with a Clinical Activity Score (CAS) of 0 or 1 in the most proptotic eye (as measured by exophthalmometer)	At Week 24
Clinical Activity Responder Rate in the most proptotic eye (as measured by exophthalmometer)	Proportion of participants with a ≥ 2 points reduction in CAS from baseline in the most proptotic eye as measured by exophthalmometer [without a corresponding increase of ≥2 points in the other eye]	At Week 24

Collaborators and Investigators

• Sponsor: Viridian Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2024
• Primary Completion (Actual): February 12, 2026
• Study Completion (Estimated): November 15, 2026

Study Registration Dates

• First Submitted: October 1, 2024
• First Submitted That Met QC Criteria: October 2, 2024
• First Posted (Actual): October 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Thyroid Eye Disease; Thyroid-Associated Ophthalmopathy; Dysthyroid Ophthalmopathy; Graves Eye Disease; Graves Orbitopathy; Myopathic Ophthalmopathy; Congestive Ophthalmopathy; Edematous Ophthalmopathy; Infiltrative Ophthalmopathy; TED; Graves
• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Graves Ophthalmopathy
• Other Study ID Numbers: VRDN-003-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No