Efficacy and Safety of Lonigutamab in Subjects With Thyroid Eye Disease (TED)

Study Overview
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Brief Summary
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Phase 1/2, multicenter, multiple dose clinical study designed to evaluate lonigutamab in subjects with TED.

Official Title
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A Phase 1/2, Adaptive, Multiple Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Clinical Efficacy of Lonigutamab in Subjects With Thyroid Eye Disease (TED)

Conditions
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Thyroid Eye Disease

Intervention / Treatment
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* Drug: lonigutamab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female, ≥18 and ≤70 years of age. Proptosis defined in the study eye as ≥3 mm above normal. Clinical Activity Score (CAS) ≥4 (using a 7-item scale) for the most severely affected eye Onset of active TED symptoms within 15 months prior to the baseline Must agree to use highly effective contraception as specified in the protocol Key Exclusion Criteria: Pathology related to inflammatory bowel disease or irritable bowel syndrome. Clinically significant pathology related to hearing or history of hearing impairment Optic neuropathy Corneal decompensation unresponsive to medical management. Previous orbital irradiation (for any cause) or any previous surgical treatment for TED. Subjects with diabetes or hemoglobin A1c >6.0% at screening Any steroid use (intravenous [IV] or oral) with a cumulative dose equivalent to >3 g of methylprednisolone for the treatment of TED within the last year. Previous steroid use (IV or oral) specifically for the treatment of TED not to exceed 1 g total dose in the 8 weeks prior to Screening. Previous use of teprotumumab or any other IGF-1 receptor (IGF-1R) inhibitor. Any previous treatment with a biologic drug for the treatment of TED (eg, rituximab and tocilizumab) Any other immunosuppressive agent within 1 month of screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Up to 3 cohorts are planned, with each cohort receiving one of 3 different treatment doses
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Single SC injection of dose 1 of lonigutamab or placebo at Day 1 and Day 21 | Drug: lonigutamab<br>* subcutaneous injection<br>Drug: Placebo<br>* subcutaneous injection<br>|
| Experimental: Cohort 2<br>multiple doses of dose 2 of lonigutamab administered SC injection weekly | Drug: lonigutamab<br>* subcutaneous injection<br>|
| Experimental: Cohort 3<br>multiple doses of lonigutamab dose 3 administered SC injection every 4 weeks. | Drug: lonigutamab<br>* subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and characterization of nonserious treatment emergent adverse events (TEAEs) | Safety and Tolerability | Day 1 to Day 163 | 
| Incidence and characterization of serious treatment emergent adverse events (TEAEs) | Safety and Tolerability | Day 1 to Day 163 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile of lonigutamab | minimum observed concentration (Cmin) | Day 1 to Day 163 | 
| PK profile of lonigutamab | Maximum observed concentration (Cmax) | Day 1 to Day 163 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TED