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

Viridian Therapeutics

Status and phase: Active, not recruiting; Phase 3

Conditions: Thyroid Eye Disease

Treatments: Drug: VRDN-001 Placebo; Drug: VRDN-001 Phase 3 Cohort (THRIVE); Drug: VRDN-001 Phase 1/2 MAD (HV and TED)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05176639

VRDN-001-101

Details and patient eligibility

About

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.

Enrollment: 154 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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 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 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 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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154 participants in 2 patient groups

Phase 1/2 MAD (HV and TED)

Experimental group

Description:

Healthy participants and participants with TED will be randomized to receive two intravenous infusions of VRDN-001 or placebo with an interval of 3 weeks.

Treatment:

Drug: VRDN-001 Phase 1/2 MAD (HV and TED)

Phase 3 Cohort (THRIVE)

Experimental group

Description:

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

Treatment:

Drug: VRDN-001 Phase 3 Cohort (THRIVE)

Drug: VRDN-001 Placebo