A Study to Investigate Efficacy and Safety of TOUR006 in Participants 18 to 75 Years of Age With Thyroid Eye Disease

Study Overview
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Brief Summary
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Phase 2b trial of TOUR006 in Thyroid Eye Disease (TED) to evaluate 20mg and 50mg doses against placebo given by a subcutaneous injection every eight weeks to TED patients who are in the active inflammatory phase of disease.

Official Title
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A Multicenter Phase 2b Randomized, Double-Masked, Placebo-Controlled Dose-Ranging Study of TOUR006 in Participants With Thyroid Eye Disease

Conditions
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Thyroid Eye Disease

Intervention / Treatment
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* Drug: TOUR006 - 20 MG
* Other: Placebo
* Drug: TOUR006 - 50 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Graves' disease associated with moderate to severe active TED Onset of active TED symptoms within approximately 12 months Proptosis (exophthalmos) ≥3 mm above the normal range (based upon race and gender) for the study eye CAS ≥4 (on the 7-item scale) for the study eye Presence of thyroid stimulating immunoglobulin (TSI) above the upper limit of normal Additional inclusion criteria are defined in the study protocol. Exclusion Criteria: Anticipated need for intervention due to sight-threatening complications or other significant and acute deterioration in vision Any previous treatment with teprotumumab or other agent that inhibits the IGF-1 receptor History of systemic steroid (oral or IV) use with a cumulative dose equivalent to ≥1 g of methylprednisolone for the treatment of TED. Previous oral steroid use with a cumulative dose of <1 g methylprednisolone (or equivalent dosage for other systemic corticosteroid) for the treatment of TED is allowed if the corticosteroid is discontinued at least 6 weeks before screening. Systemic (oral or IV) corticosteroid use for conditions other than TED within 3 months before screening. Any major illness/condition or evidence of an unstable clinical condition that, in the investigator's judgment, will substantially increase the risk to the participant, or confound the interpretation of safety assessments, if they were to participate in the study Any other condition that, in the opinion of the investigator, would impair the ability of the participant to comply with the study procedures or impair the ability to interpret data from the participant's participation in the study Pregnant or lactating Additional exclusion criteria are defined in the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TOUR006 - 20 MG<br>In part A of the study, participants will receive a total of three 20 mg subcutaneous injections: 1 injection every 8 weeks (Day 1, Week 8, Week 16) followed by treatment in part B of the study based on proptosis response and rescue therapy use. | Drug: TOUR006 - 20 MG<br>* TOUR006 20 MG<br>|
| Experimental: TOUR006 - 50 MG<br>In part A of the study, participants will receive a total of three 50 mg subcutaneous injections: 1 injection every 8 weeks (Day 1, Week 8, Week 16) followed by treatment in part B of the study based on proptosis response and rescue therapy use. | Drug: TOUR006 - 50 MG<br>* TOUR006 - 50 MG<br>|
| Placebo Comparator: Placebo<br>In part A of the study, participants will receive a total of three Placebo subcutaneous injections: 1 injection every 8 weeks (Day 1, Week 8, Week 16) followed by treatment in part B of the study based on proptosis response and rescue therapy use. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving a proptosis response defined as a ≥2 mm reduction in proptosis from baseline in the study eye without deterioration [≥2 mm increase] of proptosis in the fellow eye and without need for rescue therapy/intervention). |  | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving a proptosis response with 20mg TOUR006 administered SC every 8 weeks or 50mg TOUR006 administered SC every 8 weeks. |  | 72 weeks | 
| Percentage of participants attaining a complete or near complete response on the 7-point Clinical Activity Score (CAS). |  | 72 weeks | 
| Percentage of participants attaining ≥1 grade decrease in diplopia. |  | 72 weeks | 
| Incidence of Treatment Emergent Adverse Events by severity and Serious Adverse Events through Week 72. |  | 72 weeks | 
| Mean change from baseline in serum trough concentration of TOUR006. |  | 72 weeks | 
| Mean change from baseline in serum TSI. |  | 72 weeks | 
| Percentage of participants with anti-drug antibodies. |  | 72 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TED, Graves' Disease, Thyroid Eye Disease, Exophthalmos, Eye Diseases, Thyroid Diseases, Graves' Ophthalmopathy, Hyperthyroidism