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

Thyroid Eye Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05176639
• Other study ID #: VRDN-001-101
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 3, 2021
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: Viridian Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Please note that Phase 1/2 (HV & MAD) cohort - recruitment is completed and Phase 3 Component (THRIVE) - is actively recruiting.

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). This clinical trial will evaluate the safety, tolerability and pharmacokinetics (the concentration of drug in the blood over time) of VRDN-001 in healthy volunteers and in patients with TED. Study participants with TED will also be evaluated over time for changes in their signs and symptoms of TED compared to their baseline measurements.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 154
• Est. completion date: March 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria for Healthy Volunteers:

• Must be free of clinically significant disease or medical conditions as determined by the Investigator

• Female volunteers must not be of child-bearing potential

Key Exclusion Criteria for Healthy Volunteers:

· Must not have a history of or any evidence of diabetes mellitus, recently diagnosed renal impairment or inflammatory bowel disease, or clinically significant ear pathology or earing impairment

Key Inclusion Criteria for Participants with TED in Phase 1/2 MAD cohorts:

• Must have moderate to severe active TED with documented evidence of ocular symptoms or signs that began within 1 year prior to screening OR moderate to severe chronic TED with documented evidence of ocular symptoms or signs that began over 1 year prior to screening

• Must have active TED and a Clinical Activity Score (CAS) of = 4 on the 7-item scale for the study (more proptotic) eye OR chronic TED with no CAS requirement

• Must agree to use highly effective contraception as specified in the protocol

• Female TED participants must have a negative serum pregnancy test

Key Exclusion Criteria for Participants with TED in Phase 1/2 MAD cohorts:

• Must not have received prior treatment with another anti-IGF-1R monoclonal antibody

• Must not have used oral corticosteroids within 4 weeks prior to Day 1

• Must not have received rituximab, tocilizumab or other immunosuppressive agents within 90 days prior to Day 1

• Must not have evidence of optic nerve involvement within the previous 6 months

• Must not have corneal decompensation in the study eye unresponsive to medical management

• Must not have had previous orbital irradiation or surgery for TED in the study eye

• Must not have a history inflammatory bowel disease Must not have clinically significant ear pathology or hearing impairment

• Must not have received an investigational agent for any condition within 60 days

• Female TED participants must not be pregnant or lactating

Key Inclusion Criteria for Participants with TED in Phase 3 study:

• 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 (more proptotic) eye

• Must agree to use highly effective contraception as specified in the protocol

• Female TED participants must have a negative serum pregnancy test

Key Exclusion Criteria for Participants with TED in Phase 3 study:

• Must not have received prior treatment with another anti-IGF-1R monoclonal antibody

• Must not have used oral corticosteroids within 2 weeks prior to Day 1

• Must not have received rituximab, tocilizumab or other immunosuppressive agents within 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 inflammatory bowel disease

• Must not have a history or screening audiometry assessment of clinically significant (as determined by investigator) ear pathology, relevant ear surgery, or hearing l loss

• Must not have received an investigational agent for any condition

• Female TED participants must not be pregnant or lactating

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy
• Thyroid Diseases
• Thyroid Eye Disease

Intervention

Drug:
• VRDN-001 Phase 1/2 MAD (HV and TED)
2 Infusions of multiple ascending doses of VRDN-001, ranging from 3 mg/kg to 20 mg/kg
• VRDN-001 Phase 3 Cohort (THRIVE)
5 Infusions of VRDN-001 10mg/kg
• VRDN-001 Placebo
5 Infusions of VRDN-001 placebo

Locations

Country	Name	City	State
Australia	North Shore Private Hospital	Saint Leonards
Canada	Oshawa Clinic	Oshawa	Ontario
Canada	Ottawa Hospital Research Institute (OHRI)	Ottawa	Ontario
France	Institution: CHU d'Angers	Angers
France	H6pital Lapeyronie	Montpellier
France	Hôpital René et Guillaume Laennec	Saint-Herblain
Germany	Charité Universitaetsmedizin Berlin	Berlin
Germany	Klinik und Poliklinik für Augenheilkunde	Dresden
Germany	University Medical Center Göttingen	Göttingen
Italy	Istituto Auxologico Italiano	Milan
Netherlands	Amsterdam University Medical Center	Amsterdam
Netherlands	Erasmus MC	Rotterdam
Spain	Hospital La Arruzafa	Córdoba
Spain	Hospital La Arruzafa Avenida de la Arruzafa	Córdoba
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Ramén y Cajal. Ctra. de Colmenar,	Madrid
Spain	Hospital Universitario	Sevilla
Spain	Hospital Universitario y Politécnico La Fe Servicio Oftalmología	Valence
Spain	Hospital Universitario Miguel Servet, Servicio de Paseo Isabel La Catdlica1	Zaragoza
Turkey	Marmara University Pendik Education and Research Hospital	Pendik
Turkey	Gazi Oniversitesi Tip Fakultesi Hastanesi,	Yenimahalle
United Kingdom	Pharmacy trials unit, c/o Pharmacy Stores Level 3 Bristol Royal Infirmary	Bristol
United Kingdom	Eye Research Department South Wing St Thomas' Hospital	London
United Kingdom	Imperial College London	London
United Kingdom	Western Eye Hospital and Charing Cross Hospital	London
United States	Emory University Eye Center	Atlanta	Georgia
United States	University of Colorado - Department of Ophthalmology	Aurora	Colorado
United States	Eye Wellness Center- Neuro-Eye Clinical Trials, Inc.	Bellaire	Texas
United States	The Private Office of Raymond Douglas	Beverly Hills	California
United States	Massachusetts Eye and Ear	Boston	Massachusetts
United States	Duke Eye Center	Durham	North Carolina
United States	Ophthalmic Consultants of Boston	E. Weymouth	Massachusetts
United States	Michigan State University - Department of Neurology and Ophthalmology	East Lansing	Michigan
United States	TKL Research, Inc.	Fair Lawn	New Jersey
United States	Baylor College of Medicine - Alkek Eye Center	Houston	Texas
United States	Marshall Health Dept of Clinical & Translational Sciences	Huntington	West Virginia
United States	MACRO Trials, Inc.	Los Angeles	California
United States	USC Roski Eye Institute	Los Angeles	California
United States	University of Florida Bascom Palmer Eye Center	Miami	Florida
United States	University of Minnesota Eye Clinic	Minneapolis	Minnesota
United States	Rutgers New Jersey Medical School - Department of Ophthalmology & Visual Science	Newark	New Jersey
United States	Amy Patel Jain, MD	Newport Beach	California
United States	Byers Eye Institute/Stanford University	Palo Alto	California
United States	Department of Neuro-Ophthalmology Wills Eye Hospital	Philadelphia	Pennsylvania
United States	Scheie Eye Institute Dept of OPH University of Pennsylvania	Philadelphia	Pennsylvania
United States	UPMC Eye Center	Pittsburgh	Pennsylvania
United States	Washington University St. Louis	Saint Louis	Missouri
United States	Moran Eye Center	Salt Lake City	Utah
United States	Senta Clinic	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	Sarasota Retina Institute	Sarasota	Florida
United States	University of Washington - Department of Ophthalmology	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Viridian Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Netherlands,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	VRDN-001 concentrations in the blood over time		Up to Day 155 for MAD participants and up to Week 22 for Phase 3 subjects
Other	Incidence of anti-drug antibody (ADA) development in VRDN-001-treated subjects over time		Up to Day 155 for MAD participants and up to Week 22 for Phase 3 subjects
Primary	Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0		Up to Day 50 for MAD healthy volunteers, up to Day 169 for MAD TED subjects, and up to Week 52 for the Phase 3 study subjects
Primary	Proptosis responder rate	Proportion of TED participants with a reduction of proptosis of = 2 mm from baseline as determined by exophthalmometer	Week 6 for MAD TED participants, and Week 15 for Phase 3 study subjects
Secondary	Change from baseline in measurement of proptosis as determined by exophthalmometer		Up to Week 12 for MAD TED subjects, and up to Week 52 for Phase 3 subjects
Secondary	Change from baseline in volume of orbital fat as determined by MRI		Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary	Change from baseline in volume of extraocular muscles as determined by MRI		Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary	Change from baseline in facial fat volume as determined by MRI		Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary	Change from baseline in Clinical Activity Score (CAS)	Each of 7 clinical signs and symptoms of ocular inflammation is scored as present or absent (score of 1 or 0, respectively). The CAS is the sum of the individual scores (range from 0 to 7) where a higher score indicates a greater level of inflammation.	Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary	Change from baseline in Subjective Diplopia Score	Diplopia grade is assessed using the Gorman Subjective Diplopia Score (range from 0 to 3) based on verbal responses by the study subject. A higher score indicates a worse diplopia grade.	Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary	Change from baseline in Graves Orbitopathy-Quality of Life (GO-QoL) combined score		Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary	Change in measurement of proptosis by MRI/CT		Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects