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

A Randomized, Double-masked, Placebo-controlled Safety, Tolerability, and Efficacy Study of Veligrotug (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: Thyroid Eye Disease
• Intervention / Treatment: Drug: Veligrotug (VRDN-001); 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 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

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
    • Universitatsmedizin Gottingen
• Hungary
  • Budapest, Hungary, H-1133
    • Budapest Retina Intezet
  • Pécs, Hungary, H-7621
    • Ganglion Orvosi Központ
  • Pécs, Hungary, H-7623
    • Pécsi Tudományegyetem Klinikai Központ Szemészeti 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 Ramón 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 Politécnico La Fe
  • Zaragoza, Spain, 50009
    • Hospital Unviersitario Miguel Servet
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Üniversitesi Tip Fakültesi
  • 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, EC1V 2PD
    • Moorfield's Eye Hospital
  • London, United Kingdom, NW1 5QH
    • Imperial College Healthcare NHS Trust - Western eye Hospital
  • London, United Kingdom, SE1 7EH
    • Guy's and St. Thomas NHS Trust
  • 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

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
• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Veligrotug (VRDN-001)10 mg/kg; Drug: 5 IV Infusions of veligrotug (VRDN-001)10 mg/kg	Drug: Veligrotug (VRDN-001); Veligrotug (VRDN-001) is a humanized monoclonal antibody directed against the IGF-1 receptor
Experimental: Placebo Drug; Placebo Drug: 5 IV Infusions of placebo	Drug: Placebo; 5 IV infusions of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proptosis Responder Rate in the most proptotic eye	Proptosis Responder Rate in the most proptotic eye (i.e., reduction of proptosis of ≥2 mm from baseline [without a corresponding increase of ≥2 mm in the other eye]) as measured by exophthalmometer.	Week 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diplopia Responder Rate	Diplopia Responder Rate (i.e., reduction in Gorman Subjective Diplopia Score of ≥1 from baseline for participants with baseline Gorman Subjective Diplopia Score >0)	Week 15
Change from baseline in proptosis in the most proptotic eye	Change from baseline in proptosis in the most proptotic eye as measured by exophthalmometer	Week 15
Proptosis Responder Rate in the most proptotic eye	Change from baseline in proptosis in the most proptotic eye	Week 15
Clinical Activity Responder Rate in the most proptotic eye	Clinical Activity Responder Rate in the most proptotic eye (i.e., no worsening in CAS from baseline [without a corresponding increase of ≥2 points in the other eye]) as measured by exophthalmometer	Week 15
Overall Responder Rate in the most proptotic eye	Overall Responder Rate comprised of Proptosis Responder Rate in the most proptotic eye as measured by exophthalmometer and Clinical Activity Responder rate in the most proptotic eye as measured by exophthalmometer	Week 15
Diplopia Resolution Rate	Diplopia Resolution Rate (i.e., reduction in Gorman Subjective Diplopia Score to 0 from baseline for participants with baseline Gorman Subjective Diplopia Score > 0)	Week 15

Collaborators and Investigators

• Sponsor: Viridian Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 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 (Estimated): October 23, 2025
• Last Update Submitted That Met QC Criteria: October 22, 2025
• Last Verified: October 1, 2025

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; Graves Disease; TED; Thyroid-Associated Orbitopathy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Eye Diseases, Hereditary; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Graves Ophthalmopathy; Graves Disease
• Other Study ID Numbers: VRDN-001-301

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