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

NCT05176639 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: VRDN-001-101
• Study Type: interventional
• Target: 113
• Locations: 7 countries
• Sites: 53

Brief Summary

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 patients 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 patients who received 10 mg/kg.

Conditions

Thyroid Eye Disease

Keywords

Thyroid Eye Disease; Thyroid-Associated Ophthalmopathy; Dysthyroid Ophthalmopathy; Graves Eye Disease; Graves Orbitopathy; Myopathic Ophthalmopathy; Congestive Ophthalmopathy; Edematous Ophthalmopathy; Infiltrative Ophthalmopathy; Thyroid-Associated Orbitopathy; Graves Disease

Outcome Measures

Primary Outcomes (1)

• Proptosis Responder Rate

  Proptosis Responder Rate in the study eye (i.e., reduction of proptosis of ≥ 2 mm from baseline \[without a corresponding increase of ≥ 2 mm in the fellow eye\] as measured by exophthalmometer)

  Week 15

Secondary Outcomes (9)

• Change from baseline in proptosis in the study eye

  Week 15

• Proptosis Responder Rate in the most proptotic eye

  Week 15

• Change from baseline in proptosis in the most proptotic eye

  Week 15

• Change from baseline in CAS

  Week 15

• Overall Responder Rate

  Week 15

Study Arms (2)

Phase 3 Cohort (THRIVE) veligrotug (VRDN-001)

EXPERIMENTAL

Participants with TED will be randomized to either veligrotug (VRDN-001) 10mg/kg or placebo.

Drug: VRDN-001 Phase 3 Cohort (THRIVE)

Phase 3 Cohort (THRIVE) VRDN-001 Placebo

PLACEBO COMPARATOR

Participants with TED will be randomized to either veligrotug (VRDN-001) 10mg/kg or placebo.

Drug: VRDN-001 Placebo

Interventions

VRDN-001 Phase 3 Cohort (THRIVE) DRUG

5 IV Infusions of veligrotug (VRDN-001) 10mg/kg

Phase 3 Cohort (THRIVE) veligrotug (VRDN-001)

VRDN-001 Placebo DRUG

5 IV Infusions of veligrotug (VRDN-001) placebo

Phase 3 Cohort (THRIVE) VRDN-001 Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 with 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

Sponsors & Collaborators

• Viridian Therapeutics, Inc.: lead

Study Sites (53)

University of Colorado - Department of Ophthalmology

Aurora, California, 80045, United States

Location

The Private Office of Raymond Douglas

Beverly Hills, California, 90210, United States

Location

USC Roski Eye Institute

Los Angeles, California, 90033, United States

Location

MACRO Trials, Inc.

Los Angeles, California, 90049, United States

Location

Amy Patel Jain, MD

Newport Beach, California, 92260, United States

Location

Byers Eye Institute/Stanford University

Palo Alto, California, 94303, United States

Location

Senta Clinic

San Diego, California, 95207, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Sina Medical Center

Homestead, Florida, 33034, United States

Location

Med-Care Research Inc.

Miami, Florida, 33125, United States

Location

Edward Jenner Research Group Center LLC

Plantation, Florida, 33317, United States

Location

Sarasota Retina Institue

Sarasota, Florida, 34231, United States

Location

Vision Medical Research Inc.

Orland Park, Illinois, 60462, United States

Location

University Health Diabetes, Endocrinology & Nephrology Center

Kansas City, Kansas, 64108, United States

Location

KU Medical Center, University of Kansas

Kansas City, Kansas, 66103, United States

Location

Massachusetts Eye and Ear

Boston, Massachusetts, 02114, United States

Location

Ophthalmic Consultants of Boston

Weymouth, Massachusetts, 02189, United States

Location

Fraser Eye Care Center

Fraser, Michigan, 48026, United States

Location

Kahana Oculoplastic & Orbital Surgery

Livonia, Michigan, 48152, United States

Location

University of Minnesota, Department of Ophthalmology and Visual Neurosciences

Minneapolis, Minnesota, 55455, United States

Location

Advanced Research International, LLC

Las Vegas, Nevada, 89144, United States

Location

Rutgers-New Jersey Medical School-Newark

Newark, New Jersey, 07103, United States

Location

New York Eye Ear Infirmary of Mount Sinai

New York, New York, 10003, United States

Location

Baylor College of Medicine (BCM)-Opthalmology

Houston, Texas, 77030, United States

Location

Neuro-Eye Clinical Trials

Houston, Texas, 77074, United States

Location

Neuro-Ophthalmology of Texas PLLC

Houston, Texas, 77074, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

West Virgina University Eye Insitute

Morgantown, West Virginia, 26506, United States

Location

Sydney Eye Hospital

Sydney, 2000, Australia

Location

North Shore Eye Surgery

Sydney, 2065, Australia

Location

CHU d'Angers

Angers, 49100, France

Location

CH Nice

Nice, 06000, France

Location

Centre Hospitalier National D'ophtalmologie

Paris, 75012, France

Location

AP-HP- Hopital de la Pitie Salpetriere

Paris, 75013, France

Location

Universitatsmedizin Gottingen

Göttingen, 37075, Germany

Location

Johannes Gutenberg-University Medical Center

Mainz, 55131, Germany

Location

NZOZ E-Vita

Bialystok, 15-879, Poland

Location

Specjakistyczny Osrodek Okulistyczny Oculomedica

Bydgoszcz, 85-870, Poland

Location

Santa Familia PTG Lodz

Lodz, 90-302, Poland

Location

Panstwowy Instytut Medycsny MSWiA

Warsaw, 02-507, Poland

Location

4 Wojskowy Szpital Kliniczny z Polikinika SP ZOZ

Wroclaw, 53-114, Poland

Location

Clinica Bonanova de Cirugia Ocular

Barcelona, 08022, Spain

Location

Hospital Arruzafa

Córdoba, 14012, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Complexo Hospiralario Universitario de Santiago-Hospital Medico-Ciruxico de Conxo

Santiago, 15706, Spain

Location

Hospital Universitatio Virgen De La Macarena, Servicio de Oftalmologia

Seville, 41071, Spain

Location

Hospital Universitario Miguel Servet, Servicio de Paseo Isabel La Catdlica1

Zaragoza, 50009, Spain

Location

Northwick Park Hospital

London, United Kingdon, HA13UJ, United Kingdom

Location

Western Eye Hospital Imperial College NHS trust

London, United Kingdon, NW1 5QH, United Kingdom

Location

Guy's and St. Thomas NHS Trust

London, United Kingdon, SE1 7EH, United Kingdom

Location

MeSH Terms

Conditions

Graves Ophthalmopathy; Graves Disease

Interventions

Nicotine

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: January 4, 2022
• Study Start: December 3, 2021
• Primary Completion: July 15, 2024
• Study Completion: March 27, 2025
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8); PL (5); DE (2); AU (2); US (29); FR (4); GB (3)