A Safety, Tolerability, and Efficacy Study of Veligrotug (VRDN 001) in Participants With Thyroid Eye Disease (TED) (THRIVE)

July 22, 2026 updated by: Viridian Therapeutics, Inc.

A Safety, Tolerability, and Efficacy Study of Veligrotug, a Humanized Monoclonal Antibody Directed Against the IGF-1 Receptor in Subjects With Thyroid Eye Disease

The investigational drug, veligrotug (VRDN-001), is a monoclonal antibody that inhibits the activity of a cell surface receptor called insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R may help to reduce the inflammation and associated tissue swelling that occurs in participants with thyroid eye disease (TED). The primary objective of this clinical trial is to establish the safety, tolerability, and efficacy of veligrotug, and the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of veligrotug in active TED participants who received 10 milligrams (mg)/kilogram (kg).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

113

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Sydney, Australia, 2000
        • Sydney Eye Hospital
      • Sydney, Australia, 2065
        • North Shore Eye Surgery
  • France
      • Angers, France, 49100
        • CHU d'Angers
      • Nice, France, 06000
        • CH Nice
      • Paris, France, 75012
        • Centre Hospitalier National D'ophtalmologie
      • Paris, France, 75013
        • AP-HP- Hopital de la Pitie Salpetriere
  • Germany
      • Göttingen, Germany, 37075
        • Universitätsmedizin Göttingen
      • Mainz, Germany, 55131
        • Johannes Gutenberg-University Medical Center
  • Poland
      • Bialystok, Poland, 15-879
        • NZOZ E-Vita
      • Bydgoszcz, Poland, 85-870
        • Specjakistyczny Osrodek Okulistyczny Oculomedica
      • Lodz, Poland, 90-302
        • Santa Familia PTG Lodz
      • Warsaw, Poland, 02-507
        • Panstwowy Instytut Medycsny MSWiA
      • Wroclaw, Poland, 53-114
        • 4 Wojskowy Szpital Kliniczny z Polikinika SP ZOZ
  • Spain
      • Barcelona, Spain, 08022
        • Clinica Bonanova de Cirugia Ocular
      • Córdoba, Spain, 14012
        • Hospital Arruzafa
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain, 28027
        • Clinica Universidad de Navarra
      • Pamplona, Spain, 31008
        • Clinica Universidad de Navarra
      • Santiago, Spain, 15706
        • Complexo Hospiralario Universitario de Santiago-Hospital Medico-Ciruxico de Conxo
      • Seville, Spain, 41071
        • Hospital Universitatio Virgen De La Macarena, Servicio de Oftalmologia
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet, Servicio de Paseo Isabel La Catdlica1
  • United Kingdom
    • United Kingdon
      • London, United Kingdon, United Kingdom, HA13UJ
        • Northwick Park Hospital
      • London, United Kingdon, United Kingdom, NW1 5QH
        • Western Eye Hospital Imperial College NHS trust
      • London, United Kingdon, United Kingdom, SE1 7EH
        • Guy's and St. Thomas NHS Trust
  • United States
    • California
      • Aurora, California, United States, 80045
        • University of Colorado - Department of Ophthalmology
      • Beverly Hills, California, United States, 90210
        • The Private Office of Raymond Douglas
      • Los Angeles, California, United States, 90033
        • USC Roski Eye Institute
      • Los Angeles, California, United States, 90049
        • MACRO Trials, Inc.
      • Newport Beach, California, United States, 92260
        • Amy Patel Jain, MD
      • Palo Alto, California, United States, 94303
        • Byers Eye Institute/Stanford University
      • San Diego, California, United States, 95207
        • Senta Clinic
      • San Francisco, California, United States, 94158
        • University of California, San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Florida
      • Homestead, Florida, United States, 33034
        • Sina Medical Center
      • Miami, Florida, United States, 33125
        • Med-Care Research Inc.
      • Plantation, Florida, United States, 33317
        • Edward Jenner Research Group Center LLC
      • Sarasota, Florida, United States, 34231
        • Sarasota Retina Institute
    • Illinois
      • Orland Park, Illinois, United States, 60462
        • Vision Medical Research Inc.
    • Kansas
      • Kansas City, Kansas, United States, 64108
        • University Health Diabetes, Endocrinology & Nephrology Center
      • Kansas City, Kansas, United States, 66103
        • KU Medical Center, University of Kansas
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts Eye and Ear
      • Weymouth, Massachusetts, United States, 02189
        • Ophthalmic Consultants of Boston
    • Michigan
      • Fraser, Michigan, United States, 48026
        • Fraser Eye Care Center
      • Livonia, Michigan, United States, 48152
        • Kahana Oculoplastic & Orbital Surgery
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota, Department of Ophthalmology and Visual Neurosciences
    • Nevada
      • Las Vegas, Nevada, United States, 89144
        • Advanced Research International, LLC
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Rutgers-New Jersey Medical School-Newark
    • New York
      • New York, New York, United States, 10003
        • New York Eye Ear Infirmary of Mount Sinai
    • Texas
      • Houston, Texas, United States, 77074
        • Neuro-Eye Clinical Trials
      • Houston, Texas, United States, 77074
        • Neuro-Ophthalmology of Texas PLLC
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine (BCM)-Ophthalmology
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virgina University Eye Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria for Active TED Participants (THRIVE):

  • 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 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 for Active TED Participants (THRIVE):

  • Must not have received prior treatment with another anti-IGF-1R therapy or any investigational agent for TED
  • Must not have used systemic corticosteroids or selenium within 2 weeks prior to Day 1
  • Must not have received rituximab, tocilizumab or other immunosuppressive agents or any other therapy for TED within 8 weeks prior to Day 1
  • Must not have received an investigational agent for any condition within 8 weeks prior to Day 1
  • Must not have a pre-existing ophthalmic condition in the study eye that in the opinion of the Investigator would confound interpretation of the study results
  • Must not have had previous orbital irradiation or surgery for TED in the study eye
  • Must not have a history of inflammatory bowel disease
  • Must not have a history of or screening audiometry assessment of clinically significant (as determined by investigator) ear pathology, relevant ear surgery, or hearing loss
  • Female TED participants must not be pregnant or lactating

Note: Prior thyroidectomy, radioactive iodine (RAI) treatment, or orbital decompression surgery limited to bone only are NOT exclusions.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Veligrotug
Participants will receive veligrotug 10 mg/kg as an intravenous (IV) infusion every 3 weeks (Q3W) for 12 weeks.
Drug: Veligrotug
5 IV Infusions of veligrotug 10 mg/kg
Other Names:
  • VRDN-001
Placebo Comparator: Placebo
Participants will receive placebo matched to veligrotug as an IV infusion Q3W for 12 weeks.
Drug: Placebo
5 IV Infusions of veligrotug matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proptosis Responder Rate (PRR) in the Study Eye As Measured by Exophthalmometer
Time Frame: Baseline to Week 15
Proptosis responder in the study eye was defined as a reduction of proptosis of ≥2 millimeters (mm) from baseline in the study eye (without a corresponding increase of ≥2 mm in the fellow eye) as measured by exophthalmometer. Missing data were imputed with the Multiple Imputation method.
Baseline to Week 15

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Proptosis in the Study Eye As Measured by Exophthalmometer
Time Frame: Baseline, Week 15
Proptosis was defined as distance between the lateral orbital rim and the most anterior position of the cornea in mm, measured using an exophthalmometer. Missing data were imputed with the Multiple Imputation method.
Baseline, Week 15
PRR in the Most Proptotic Eye As Measured by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT)
Time Frame: Week 15
Proptosis responder in the most proptotic eye by MRI/CT was defined as a reduction of proptosis of ≥2 mm from baseline in the most proptotic eye by MRI/CT (without a corresponding increase of ≥2 mm in the other eye) as measured by MRI/CT. Missing data were imputed using the Exophthalmometer Imputation method, as applicable.
Week 15
Change From Baseline in Proptosis in the Most Proptotic Eye As Measured by MRI/CT
Time Frame: Baseline, Week 15
Measurement of proptosis conducted by the central imaging reading center using MRI/CT of the orbits acquired without contrast. Measurements were conducted by 2 independent readers with adjudication if the difference between the 2 primary readers in proptosis measurement exceeded 5% (calculated as the difference divided by the larger measurement). The average of 2 (or 3 if adjudicated) measurements were used for analyses. Missing data were imputed using the Exophthalmometer Imputation method, as applicable.
Baseline, Week 15
Change From Baseline in CAS in the Study Eye
Time Frame: Baseline, Week 15
The CAS was based on 7 components: spontaneous retrobulbar pain, pain on attempted eye movements (upward, side to-side, and downward gazes), conjunctival redness, redness of the eyelids, chemosis, swelling of the caruncle or plica and swelling of the eyelids. Each component was scored as present or absent (scored as 1 or 0, respectively), and the CAS was given as the sum of the scores (range, 0 to 7, with higher scores indicating greater level of inflammation). Missing data were imputed with the Multiple Imputation method.
Baseline, Week 15
Overall Responder Rate (ORR) Comprising of PRR and Clinical Activity Responder Rate in the Study Eye
Time Frame: Baseline to Week 15
ORR in the study eye was comprised of PRR in the study eye (reduction of proptosis of ≥ 2 mm from baseline [without a corresponding increase of ≥ 2 mm in the fellow eye]) and clinical activity responder in the study eye (reduction in clinical activity score [CAS] ≥ 2 points from baseline [without a corresponding increase of ≥ 2 points in the fellow eye]). CAS ranged from 0 to 7, with higher scores indicating greater level of inflammation. Proptosis (distance between the lateral orbital rim and the most anterior position of the cornea in mm) was measured using an exophthalmometer. Missing data were imputed with Multiple Imputation method.
Baseline to Week 15
Clinical Activity Responder Rate in the Study Eye
Time Frame: Week 15
Clinical activity responder rate in the study eye was defined as a reduction in CAS ≥2 points from baseline in the study eye (without a corresponding increase of ≥2 points in the fellow eye). Missing data were imputed with the Multiple Imputation method.
Week 15
Diplopia Responder Rate
Time Frame: Week 15
Diplopia responder was defined as reduction in Gorman subjective diplopia score of ≥1 from baseline for participants with baseline Gorman subjective diplopia score >0. Gorman subjective diplopia score (range, 0 to 3) includes 4 categories: no diplopia (absent, scored as 0), diplopia in the primary position of gaze when the participant is tired or awakening (intermittent, scored as 1), diplopia at extremes of gaze (inconstant, scored as 2), and continuous diplopia in the primary or reading position (constant, scored as 3). Missing data were imputed with the Multiple Imputation method.
Week 15
Diplopia Resolution Rate
Time Frame: Week 15
Diplopia resolution was defined as reduction in Gorman subjective diplopia score to 0 from baseline for participants with baseline Gorman subjective diplopia score >0. Gorman subjective diplopia score (range, 0 to 3) includes 4 categories: no diplopia (absent, scored as 0), diplopia in the primary position of gaze when the participant is tired or awakening (intermittent, scored as 1), diplopia at extremes of gaze (inconstant, scored as 2), and continuous diplopia in the primary or reading position (constant, scored as 3). Missing data were imputed with the Multiple Imputation method.
Week 15
Percentage of Participants With a CAS of 0 or 1 in the Study Eye
Time Frame: Week 15
The CAS was based on 7 components: spontaneous retrobulbar pain, pain on attempted eye movements (upward, side to-side, and downward gazes), conjunctival redness, redness of the eyelids, chemosis, swelling of the caruncle or plica and swelling of the eyelids. Each component was scored as present or absent (scored as 1 or 0, respectively), and the CAS was given as the sum of the scores (range, 0 to 7, with higher scores indicating greater level of inflammation). Missing data were imputed with the Multiple Imputation method.
Week 15

Other Outcome Measures

Outcome Measure
Time Frame
Veligrotug (VRDN-001) concentrations in the blood over time
Time Frame: Up to Day 50 for HV and TED MAD participants, and up to Week 24 for Phase 3 participants
Up to Day 50 for HV and TED MAD participants, and up to Week 24 for Phase 3 participants
Incidence of anti-drug antibody (ADA) development in veligrotug (VRDN-001)-treated participants over time
Time Frame: Up to Day 50 for HV and TED MAD participants, and up to Week 24 for Phase 3 participants
Up to Day 50 for HV and TED MAD participants, and up to Week 24 for Phase 3 participants

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Viridian Therapeutics, Inc.

Investigators

  • Study Director: Thomas Ciulla, MD, MBA, Viridian Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 16, 2022

Primary Completion (Actual)

July 15, 2024

Study Completion (Actual)

March 27, 2025

Study Registration Dates

First Submitted

December 15, 2021

First Submitted That Met QC Criteria

December 15, 2021

First Posted (Actual)

January 4, 2022

Study Record Updates

Last Update Posted (Actual)

August 13, 2026

Last Update Submitted That Met QC Criteria

July 22, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VRDN-001-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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