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

A Multiple Ascending Dose (MAD) Safety, Tolerability and Efficacy Study of Veligrotug (VRDN-001), a Humanized Monoclonal Antibody Directed Against the IGF-1 Receptor, in Normal Healthy Volunteers (NHV(s) and Subjects With Thyroid Eye Disease (TED)

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.

Study Overview

• Status: Completed
• Conditions: Thyroid Eye Disease
• Intervention / Treatment: Drug: VRDN-001 Phase 3 Cohort (THRIVE); Drug: VRDN-001 Placebo

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 3

Contacts and Locations

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
  • Gottingen, Germany, 37075
    • Universitatsmedizin Gottingen
  • 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
  • Warszawa, 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
  • Cordoba, Spain, 14012
    • Hospital Arruzafa
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon 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
  • Sevilla, 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 Institue
  • 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, 77030
      • Baylor College of Medicine (BCM)-Opthalmology
    • Houston, Texas, United States, 77074
      • Neuro-Ophthalmology of Texas PLLC
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virgina University Eye Insitute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

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 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

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

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: Phase 3 Cohort (THRIVE) veligrotug (VRDN-001); Participants with TED will be randomized to either veligrotug (VRDN-001) 10mg/kg or placebo.	Drug: VRDN-001 Phase 3 Cohort (THRIVE); 5 IV Infusions of veligrotug (VRDN-001) 10mg/kg
Placebo Comparator: Phase 3 Cohort (THRIVE) VRDN-001 Placebo; Participants with TED will be randomized to either veligrotug (VRDN-001) 10mg/kg or placebo.	Drug: VRDN-001 Placebo; 5 IV Infusions of veligrotug (VRDN-001) placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Activity Responder Rate in the study eye	Clinical Activity Responder Rate in the study eye	Week 15
Change from baseline in proptosis in the study eye	Change from baseline in proptosis in the study eye as measured by exophthalmometer	Week 15
Proptosis Responder Rate in the most proptotic eye	Proptosis Responder Rate in the most proptotic eye as measured by MRI/CT	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 MRI/CT	Week 15
Change from baseline in CAS	Change from baseline in Clinical Activity Score (CAS) in the study eye	Week 15
Overall Responder Rate	Overall Responder Rate comprising Proptosis Responder Rate as measured by exophthalmometer and Clinical Activity Responder Rate in the study eye	Week 15
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
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
Proportion of participants with a CAS score of zero or one in the study eye	Proportion of participants with a CAS of zero or one in the study eye	Week 15

Other Outcome Measures

Outcome Measure	Time Frame
Veligrotug (VRDN-001) concentrations in the blood over time	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	Up to Day 50 for HV and TED MAD participants, and up to Week 24 for Phase 3 participants

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2021
• 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): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: July 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; Thyroid-Associated Orbitopathy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Eye Diseases; Graves Ophthalmopathy; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• 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