A Randomized, Double-masked, Placebo-controlled Safety, Tolerability, and Efficacy Study of VRDN-001, a Humanized Monoclonal Antibody Directed Against the IGF-1 Receptor, in Participants With Chronic Thyroid Eye Disease (TED)

Study Overview
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Brief Summary
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A randomized, double-masked, placebo-controlled safety, tolerability and efficacy study of VRDN-001 in participants with chronic thyroid eye disease (TED)

Detailed Description
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A randomized, double-masked, placebo-controlled safety, tolerability and efficacy study of VRDN-001, a humanized monoclonal antibody directed against the IGF-1 receptor, in participants with chronic thyroid eye disease (TED)

Official Title
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A Randomized, Double-masked, Placebo-controlled Safety, Tolerability, and Efficacy Study of VRDN-001, a Humanized Monoclonal Antibody Directed Against the IGF-1 Receptor, in Participants With Chronic Thyroid Eye Disease (TED)

Conditions
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Thyroid Eye Disease

Intervention / Treatment
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* Drug: VRDN-001 10 mg/kg Drug:


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have moderate to severe chronic TED with documented evidence of ocular symptoms or signs that began > 15 months prior to screening Must have Clinical Activity Score (CAS) of (0-7) 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: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VRDN-001 10 mg/kg<br>Drug: 5 Infusions of VRDN-001 10 mg/kg | Drug: VRDN-001 10 mg/kg Drug:<br>* Drug: 5 Infusions of VRDN-001 10mg/ Placebo: 5 Infusions of placebo<br>|
| Experimental: Placebo Drug<br>Placebo Drug: 5 Infusions of placebo | Drug: VRDN-001 10 mg/kg Drug:<br>* Drug: 5 Infusions of VRDN-001 10mg/ Placebo: 5 Infusions of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proptosis Responder Rate in the study eye | 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) at 3 weeks post the fifth infusion (i.e., Week 15) | 3 weeks post the fifth infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in proptosis in the study eye at Week 15 | Change from Baseline in proptosis in the study eye as measured by exophthalmometer at Week 15 | Week 15 | 
| Clinical Activity Responder Rate in the study eye | Clinical Activity Responder Rate in the study eye | Week 15 | 
| Change from baseline in CAS in the study eye | Change from baseline in CAS in the study eye | Week 15 | 
| Overall Response Rate in the study eye | Overall Response Rate in the study eye | Week 15 | 
| Diplopia Resolution Rate | Diplopia Resolution Rate (i.e., reduction in Diplopia Score to 0 from baseline for participants with baseline Diplopia Score >0) at Week 15 | Week 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graves, Thyroid Eye Disease, Thyroid-Associated Ophthalmopathy, Dysthyroid Ophthalmopathy, Graves Eye Disease, Graves Orbitopathy, Myopathic Ophthalmopathy, Congestive Ophthalmopathy, Edematous Ophthalmopathy, Infiltrative Ophthalmopathy