An Efficacy, Safety, and Tolerability Study of Veligrotug (VRDN-001), in Participants With Chronic Thyroid Eye Disease (TED) (THRIVE-2)

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

A Randomized, Double-masked, Placebo-controlled Safety, Tolerability, and Efficacy Study of VRDN-001, a Humanized Monoclonal Antibody Directed Against the IGF-1 Receptor, in Participants With Chronic Thyroid Eye Disease (TED)

This is a clinical trial assessing the efficacy, safety, and tolerability of an investigational drug, veligrotug (VRDN-001), in participants with chronic thyroid eye disease (TED).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 chronic TED. The key objectives of this study are to determine if veligrotug (VRDN-001) is efficacious, safe, and tolerable when administered as 5 IV infusions given every 3 weeks for a total of 12 weeks in participants with chronic TED.

Study Type

Interventional

Enrollment (Actual)

188

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
    • New South Wales
      • Saint Leonards, New South Wales, Australia, 2065
        • North Shore Private Hospital
  • France
      • Angers, France, 49033
        • CHU Angers
      • Bordeaux, France, 33000
        • CHU de Bordeaux - Hôpital Saint-André
      • Nantes, France, 44093
        • Centre Hospitalier Universitaire De Nantes - G. R. Laennec
      • Nice, France, 06000
        • CH Nice
  • Germany
      • Berlin, Germany, 13353
        • Charité - Universitätsmedizin Berlin KöR
      • Essen, Germany, 45122
        • Universitätsklinikum Essen AöR
      • Freiburg im Breisgau, Germany, 79106
        • University Medical Center Freiburg
      • Göttingen, Germany, 37075
        • Universitätsmedizin Göttingen
  • Hungary
      • Budapest, Hungary, H-1133
        • Budapest Retina Intezet
      • Pécs, Hungary, H-7621
        • Ganglion Orvosi Kozpont
      • Pécs, Hungary, H-7623
        • Pecsi Tudomanyegyetem Klinikai Kozpont Szemeszeti Klinika
  • Poland
      • Bialystok, Poland, 15-276
        • Uniwersytecki Szpital Kliniczny w Bialymstoku
      • Bialystok, Poland, 85-157
        • Oculomedica Sp. z o.o.
      • Gdansk, Poland, 80-809
        • Optimum Profesorskie Centrum Okulistyki sp. z o.o.
      • Piaseczno, Poland, 05-500
        • Centrum Medyczne Pulawska Sp. z o.o.
      • Wałbrzych, Poland, 58-304
        • Centrum Medyczne Piasta 47 sp. z o.o.
  • Spain
      • A Coruña, Spain, 15706
        • Complexo Hospitalario Universitario de Santiago-Hospital Médico-Cirúrxico de Conxo
      • Barcelona, Spain, 08021
        • Centro de Oftalmologia Barraquer (Barraquer Ophthalmology Centre)
      • Córdoba, Spain, 14012
        • Hospital La Arruzafa
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocío
      • Seville, Spain, 41009
        • Hospital Universitario Virgen De La Macarena
      • Valencia, Spain, 46026
        • Hospital Universitario y Politecnico La Fe
      • Zaragoza, Spain, 50009
        • Hospital Unviersitario Miguel Servet
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 06230
        • Hacettepe Universitesi Tip Fakultesi
      • Ankara, Turkey (Türkiye), 06500
        • Gazi University Medical Faculty Hospital
      • Antalya, Turkey (Türkiye), 07059
        • Akdeniz University Medical Faculty Hospital
      • Istanbul, Turkey (Türkiye), 34854
        • Marmara University Faculty of Medicine
  • United Kingdom
      • London, United Kingdom, SE1 7EH
        • St. Thomas' Hospital
      • London, United Kingdom, EC1V 2PD
        • Moorfields Eye Hospital
      • London, United Kingdom, NW1 5QH
        • Imperial College Healthcare NHS Trust - Western eye Hospital
      • Newcastle, United Kingdom, NEI 4LP
        • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      • Southampton, United Kingdom, SO16 6YD
        • University Hospital Southampton NHS Foundation Trust
  • United States
    • California
      • Los Angeles, California, United States, 90023
        • Advancing Research International, LLC
      • Los Angeles, California, United States, 90089
        • USC Roski Eye Institute
      • Newport Beach, California, United States, 92660
        • Amy Patel Jain, MD
      • Palo Alto, California, United States, 94303
        • Stanford Byers Eye Institute
      • San Diego, California, United States, 92108
        • Cockerham Eye Consultants, PC
    • Florida
      • Miami, Florida, United States, 33136
        • Bascom Palmer Eye Institute - Ophthalmology - Miami
      • Sarasota, Florida, United States, 34239
        • Sarasota Retina Institute
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Oak Lawn, Illinois, United States, 60453
        • Family Eye Physicians, Ltd
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts Eye and Ear
      • Boston, Massachusetts, United States, 02189
        • Ophthalmic Consultants of Boston
    • Michigan
      • East Lansing, Michigan, United States, 48824
        • Michigan State University, Department of Neurology
      • Livonia, Michigan, United States, 48152
        • Kahana Oculoplastic and Orbital Surgery
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine in St Louis - Ophthalmology
    • Nevada
      • Las Vegas, Nevada, United States, 89144
        • Steven Leibowitz, MD.
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Rutgers - New Jersey Medical School
      • Somerset, New Jersey, United States, 08873
        • The Center for Eye and Facial Plastic Surgery
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Wills Eye Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Department of Ophthalmology, University of Pennsylvania
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine (BCM) - Ophthalmology
      • Houston, Texas, United States, 77074
        • Neuro Eye Clinical Trials
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Harborview Medical Center

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Must have moderate to severe chronic TED with documented evidence of ocular symptoms or signs that began greater than 15 months prior to screening
  • Must have had a clinical diagnosis of TED, with any CAS (0-7)
  • 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 for any condition, including TED, or selenium within 2 weeks prior to first dose
  • Must not have received other immunosuppressive drugs or another investigational agent for any condition, including TED, or any other therapy for TED, within 8 weeks prior to first dose
  • Must not have received radioactive iodine (RAI) treatment within 8 weeks prior to first dose
  • Must not have a pre-existing ophthalmic condition in the study eye that in the opinion of the study doctor would confound interpretation of the study results
  • Must not have had previous orbital irradiation or decompression surgery for TED to the study eye's orbit
  • Must not have inflammatory bowel disease
  • Must not have abnormal baseline audiometry Pure Tone Average (PTA) assessment or history of significant (as determined by the Investigator) ear pathology, relevant ear surgery or hearing loss.
  • Female TED participants must not be pregnant or lactating

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
Experimental: 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 Most Proptotic Eye as Measured by Exophthalmometer
Time Frame: Baseline to Week 15
Proptosis response in the most proptotic eye was defined as a reduction of proptosis of ≥2 millimeters (mm) from baseline in the most proptotic eye (without a corresponding increase of ≥2 mm in the other eye) as measured by exophthalmometer. Missing data were imputed with the Multiple Imputation (MI) method.
Baseline to Week 15

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Proptosis in the Most Proptotic 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 MI method.
Baseline, Week 15
PRR in the Most Proptotic Eye, as Measured by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT)
Time Frame: Baseline to 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 (EXI) method, as applicable.
Baseline to 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 was 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 EXI method, as applicable.
Baseline, Week 15
Clinical Activity Responder Rate in the Most Proptotic Eye as Measured by Exophthalmometer
Time Frame: Week 15
Clinical activity responder in the most proptotic eye was defined as no worsening in clinical activity score (CAS) from baseline in the most proptotic eye without a corresponding increase of ≥2 points in the other eye. Missing data were imputed with the MI method.
Week 15
Overall Responder Rate (ORR) Comprising PRR and Clinical Activity Responder Rate in the Most Proptotic Eye as Measured by Exophthalmometer
Time Frame: Baseline to Week 15
ORR was comprised of PRR in the most proptotic eye (reduction of proptosis of ≥2 mm from baseline in the most proptotic eye [without a corresponding increase of ≥2 mm in the other eye]) as measured by exophthalmometer at Week 15 and Clinical Activity Responder rate in the most proptotic eye (no worsening in CAS from baseline in the most proptotic eye without a corresponding increase of ≥2 points in the other eye) as measured by exophthalmometer at Week 15. Missing data were imputed with the MI method.
Baseline to Week 15
Diplopia Responder Rate
Time Frame: Week 15
A diplopia responder was defined as having a decrease of ≥1 from baseline for participants with a 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 MI 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 MI method.
Week 15

Collaborators and Investigators

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

Sponsor

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 1, 2023

Primary Completion (Actual)

November 4, 2024

Study Completion (Actual)

July 25, 2025

Study Registration Dates

First Submitted

August 25, 2023

First Submitted That Met QC Criteria

August 25, 2023

First Posted (Actual)

September 1, 2023

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-001-301

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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