An Open-label Study (OLE) for Non-responders of VRDN-001-101 (NCT05176639) and VRDN-001-301 (NCT06021054) (OLE)

An Open-label Study for Participants Who Are Non-responders at the End of Treatment Assessment on the VRDN-001-101 and VRDN-001-301 Pivotal Studies

The investigational drug, 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 objectives of this clinical trial are to provide open-label access to VRDN-001 for participants who were previously non-responders at 3 weeks post the fifth IV infusion (i.e., 15 weeks) in the VRDN-001-101 (THRIVE) and VRDN-001-301 (THRIVE-2) pivotal studies and assess the safety and efficacy of VRDN-001 in participants who were previously treated with VRDN-001 or placebo.

Study Overview

• Status: Completed
• Conditions: Thyroid Eye Disease
• Intervention / Treatment: Drug: Veligrotug

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • CHU Angers
  • Hérault
    • Montpellier, Hérault, France, 34295
      • Centre Hospitalier Universitaire de Montpellier Hopital Lapeyronie
  • Loire-Atlantique
    • Saint-Herblain, Loire-Atlantique, France, 44800
      • Centre Hospitalier Universitaire De Nantes G.R. Laenne
• Germany
  • Berlin, Germany
    • Charite - Universitatsmedizin Berlin KoR, Campus Virchow Klinikum, Klinik tor Augenheilkunde
  • Dresden, Germany
    • Universitätsklinikum Carl Gustav Carus
  • Essen, Germany
    • Universitatsklinikum Essen AoR - Klinik fur Augenheilkunde
  • Freiburg im Breisgau, Germany
    • University Medical Center Freiburg
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany, 37075
      • Universitatmedizin Gottingen
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Gdansk, Poland, 80809
    • Optimum Profesorskie Centrum Okulistyki
  • Piaseczno, Poland, 05-500
    • Centrum Medyczne Pulawska
  • Piasta
    • Wałbrzych, Piasta, Poland, 58-304
      • Centrum Medyczne Piasta
• Spain
  • Córdoba, Spain, 14012
    • Hospital Arruzafa. Servicio de Oftalmologia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Seville, Spain, 41009
    • Hospital Universitario Virgen De La Macarena
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servel
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Universitesi Tip Fakultesi
  • Ankara, Turkey (Türkiye), 06560
    • Gazi University Medical Faculty Hospital
  • Antalya, Turkey (Türkiye), 7070
    • Akdeniz University Medical Faculty Hospital
  • Istanbul, Turkey (Türkiye), 34899
    • Marmara University Faculty of Medicine
• United Kingdom
  • Bristol, United Kingdom
    • University Hospital Bristol and Weston NHS Foundation Trust- Bristol Eye Hospital
  • London, United Kingdom, NW15QH
    • Imperial College Healthcare NHS Trust Western Eye Hospital
  • London, United Kingdom, SE17EH
    • Guy's and St. Thomas Trust
  • Newcastle, United Kingdom
    • Newcastle Eye Centre
  • London
    • Norwich, London, United Kingdom
      • Norfolk and Norwich University Hospital NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Eye Institute
    • Los Angeles, California, United States, 90023
      • Advancing Research International, LLC
    • Newport Beach, California, United States, 90023
      • Advancing Research International, LLC
    • 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
      • University of Miami Miller School of Medicine, Bascom Palmer Eye Institute
    • Sarasota, Florida, United States, 34239
      • Sarasota Retina Institute
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Vision Medical Research
  • Massachusetts
    • East Weymouth, Massachusetts, United States, 02189
      • Ophthalmic Consultants of Boston
  • Michigan
    • Livonia, Michigan, United States, 48152
      • Kahana Oculoplastic & Orbital Surgery
  • Nevada
    • Las Vegas, Nevada, United States, 89144
      • Ophthalmic Plastic, Reconstructive, Orbital and Cosmetic Surgery
  • 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, 19104
      • Hospital of the University of Pennsylvania Perleman Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • 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, 98104-2430
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Be able to understand the study procedures and the risks involved and be willing to provide written informed consent before the first study-related activity
2. Have completed at least 5 IV infusions and assessments required to determine proptosis responder status 3 weeks post the fifth IV infusion (i.e., Week 15) as defined in either the VRDN-001-101 or VRDN-001-301 pivotal studies
3. Been a participant in either the VRDN-001-101 or VRDN-001-301 studies and found to be a non-responder as defined within the VRDN-001-101 or VRDN-001-301 study
4. Not require immediate surgical ophthalmological or orbital surgery in the study eye for any reason
5. Must agree to use highly effective contraception as specified in the protocol
6. Female TED participants must have a negative urine pregnancy test at screening
7. Be willing and able to comply with all the requirements of the protocol for the entire duration of the study

Key Exclusion Criteria:

Participants must not:

1. Have received prior treatment with another anti-IGF-1R agent
2. Have received systemic corticosteroids for any condition, including TED, or selenium within 2 weeks prior to first dose
3. Have received other immunosuppressive drugs or another investigational agent for any condition, including TED (other than VRDN-001 or placebo associated with the VRDN-001-101 or VRDN-001-301 pivotal studies), or any other therapy for TED, within 8 weeks prior to first dose
4. Have received radioactive iodine (RAI) treatment within 8 weeks prior to first dose
5. Have had previous orbital irradiation or decompression surgery involving excision of fat for TED to the study eye's orbit
6. Have abnormal hearing test before first dose. Have a history of ear conditions considered significant by study doctor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Veligrotug 10 mg/kg; 5 infusions of Veligrotug 10 mg/kg	Drug: Veligrotug; Veligrotug 10 mg/kg (5 infusions of Veligrotug 10 mg/kg); Other Names: VRDN-001

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
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 proptosis in the most proptotic eye	Change from Baseline in proptosis in the most proptotic eye as measured by exophthalmometer	Week 15
Clinical Activity Responder Rate in the most proptotic eye	Clinical Activity Responder Rate in the most proptotic eye as measured by exophthalmometer	Week 15
Overall Responder Rate in the most proptotic eye	Overall 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 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

Collaborators and Investigators

• Sponsor: Viridian Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2024
• Primary Completion (Actual): April 25, 2025
• Study Completion (Actual): June 23, 2025

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: December 21, 2023
• First Posted (Actual): December 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

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
• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Graves Ophthalmopathy; Investigative Techniques; Methods; Therapeutics
• Other Study ID Numbers: VRDN-001-302

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