Clinical trial NCT05176639: A Safety, Tolerability and Efficacy Study of Veligrotug (VRDN 001) in Healthy Volunteers and Participants with Thyroid Eye Disease (TED) ( THRIVE )
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Thyroid Eye Disease
Keywords: Graves Ophthalmopathy
Thyroid Eye Disease
Thyroid-Associated Ophthalmopathy
Dysthyroid Ophthalmopathy
Graves Eye Disease
Graves Orbitopathy
Myopathic Ophthalmopathy
Congestive Ophthalmopathy
Edematous Ophthalmopathy
Infiltrative Ophthalmopathy
Lead sponsor: Viridian Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-04
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Please note that Phase 1/2 (HV \&amp;amp;amp ; TED MAD) cohorts and Phase 3 component (THRIVE) - recruitment is complete.

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). This clinical trial will evaluate the safety, tolerability and pharmacokinetics (the concentration of drug in the blood over time) of veligrotug (VRDN-001) in healthy volunteers (HV) 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.


Eligibility criteria: 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 hearing 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 systemic 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 of 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 systemic 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 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
* Must not have received an investigational agent for any condition
* Female TED participants must not be pregnant or lactating

Primary outcomes:
measure: Proptosis Responder Rate in the study eye
timeFrame: Week 6 for TED MAD participants, and Week 15 for Phase 3 participants
measure: Incidence of treatment-emergent adverse events
timeFrame: Up to Day 50 for HV MAD
Secondary outcomes:
measure: Change from baseline in proptosis in the study eye as measured by exophthalmometer
timeFrame: Week 6 for TED MAD participants, and Week 15 for Phase 3 participants
measure: Proptosis Responder Rate in the most proptotic eye as measured by MRI/CT
timeFrame: Week 15 for Phase 3 participants
measure: Change from baseline in proptosis in the most proptotic eye as measured by MRI/CT
timeFrame: Week 15 for Phase 3 participants
measure: Change from baseline in Clinical Activity Score (CAS)
timeFrame: Week 6 for TED MAD participants, and Week 15 for Phase 3 participants
measure: Overall Responder Rate comprising Proptosis Responder Rate as measured by exophthalmometer and Clinical Activity Responder Rate in the study eye
timeFrame: Week 6 for TED MAD participants, and Week 15 for Phase 3 participants
measure: Clinical Activity Responder Rate in the study eye
timeFrame: Week 6 for TED MAD participants, and Week 15 for Phase 3 participants
measure: Diplopia Responder Rate
timeFrame: Week 6 for TED MAD participants, and Week 15 for Phase 3 participants
measure: Diplopia Resolution Rate
timeFrame: Week 6 for TED MAD participants, and Week 15 for Phase 3 participants
measure: Proportion of participants with a CAS of zero or one in the study eye
timeFrame: Week 6 for TED MAD participants, and Week 15 for Phase 3 participants
Other outcomes:
measure: Veligrotug (VRDN-001) concentrations in the blood over time
timeFrame: Up to Day 50 for HV and TED MAD participants, and up to Week 24 for Phase 3 participants
measure: Incidence of anti-drug antibody (ADA) development in veligrotug (VRDN-001)-treated participants over time
timeFrame: Up to Day 50 for HV and TED MAD participants, and up to Week 24 for Phase 3 participants
Locations:
city: Beverly Hills
country: United States
facility: The Private Office of Raymond Douglas
state: California
city: Los Angeles
country: United States
facility: USC Roski Eye Institute
state: California
city: Los Angeles
country: United States
facility: MACRO Trials, Inc.
state: California
city: Newport Beach
country: United States
facility: Amy Patel Jain, MD
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute/Stanford University
state: California
city: San Diego
country: United States
facility: Senta Clinic
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado - Department of Ophthalmology
state: Colorado
city: Miami
country: United States
facility: University of Florida Bascom Palmer Eye Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Retina Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Eye Center
state: Georgia
city: Boston
country: United States
facility: Massachusetts Eye and Ear
state: Massachusetts
city: East Weymouth
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University - Department of Neurology and Ophthalmology
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Eye Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: Newark
country: United States
facility: Rutgers New Jersey Medical School - Department of Ophthalmology & Visual Science
state: New Jersey
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Philadelphia
country: United States
facility: Scheie Eye Institute Dept of OPH University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Department of Neuro-Ophthalmology Wills Eye Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Eye Center
state: Pennsylvania
city: Bellaire
country: United States
facility: Eye Wellness Center- Neuro-Eye Clinical Trials, Inc.
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Alkek Eye Center
state: Texas
city: Salt Lake City
country: United States
facility: Moran Eye Center
state: Utah
city: Seattle
country: United States
facility: University of Washington - Department of Ophthalmology
state: Washington
city: Saint Leonards
country: Australia
facility: North Shore Private Hospital
city: Oshawa
country: Canada
facility: Oshawa Clinic
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute (OHRI)
state: Ontario
city: Angers
country: France
facility: Institution: CHU d'Angers
city: Montpellier
country: France
facility: Hospital Lapeyronie
city: Saint-Herblain
country: France
facility: Hôpital René et Guillaume Laennec
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin
city: Dresden
country: Germany
facility: Klinik und Poliklinik für Augenheilkunde
city: Göttingen
country: Germany
facility: University Medical Center Göttingen
city: Milan
country: Italy
facility: Istituto Auxologico Italiano
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Córdoba
country: Spain
facility: Hospital La Arruzafa Avenida de la Arruzafa
city: Córdoba
country: Spain
facility: Hospital La Arruzafa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal. Ctra. de Colmenar,
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Sevilla
country: Spain
facility: Hospital Universitario
city: Valence
country: Spain
facility: Hospital Universitario y Politécnico La Fe Servicio Oftalmología
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet, Servicio de Paseo Isabel La Catdlica1
city: Pendik
country: Turkey
facility: Marmara University Pendik Education and Research Hospital
city: Yenimahalle
country: Turkey
facility: Gazi Oniversitesi Tip Fakultesi Hastanesi,
city: Bristol
country: United Kingdom
facility: Pharmacy trials unit, c/o Pharmacy Stores Level 3 Bristol Royal Infirmary
city: London
country: United Kingdom
facility: Eye Research Department South Wing St Thomas' Hospital
city: London
country: United Kingdom
facility: Western Eye Hospital and Charing Cross Hospital
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: Viridian Therapeutics, Inc.
name: Thomas Ciulla, MD, MBA
role: STUDY_DIRECTOR
References: