Study to Assess Batoclimab in Participants With Active Thyroid Eye Disease

Study Overview
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Brief Summary
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To evaluate the efficacy of batoclimab 680 milligrams (mg) subcutaneous (SC) once a week (QW) for 12 weeks followed by 340 mg SC QW for 12 weeks versus placebo on proptosis responder rate at Week 24.

Official Title
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A Phase 3, Multi-center, Randomized, Quadruple-masked, Placebo-controlled Study of Batoclimab for the Treatment of Participants With Active Thyroid Eye Disease (TED)

Conditions
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Thyroid Eye Disease

Intervention / Treatment
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* Drug: Batoclimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Are ≥18 years of age at screening. Have a clinical diagnosis of TED associated with active, moderate to severe TED with the following at screening and Visit 0: A CAS ≥ 4 in either eye, and Clinical evidence of worsened proptosis with: Proptosis ≥ 18 mm and/or Proptosis ≥ 3 mm increase from participant's baseline (prior to diagnosis of TED), as estimated by the Investigator/assessor Have moderate to severe active TED, as defined by European Group on Graves' Orbitopathy (EUGOGO) guidelines. Have onset of active TED within 12 months prior to screening. Have documented evidence of detectable anti-TSHR-Ab at screening. Are not expected to require immediate surgical intervention and are not planning corrective surgery/irradiation or medical therapy for TED during the course of the study. Are euthyroid with the Baseline disease under control or have mild hypo- or hyperthyroidism. Additional inclusion criteria are defined in the protocol. Exclusion criteria: Have decreased best corrected visual acuity due to optic neuropathy. Have at least a 2-point decrease in CAS or ≥2 mm decrease in proptosis between screening and Baseline assessments in either eye. Have used any steroid (intravenous or oral) for the treatment of TED or other conditions within 4 weeks prior to screening. Have used any steroid (Intravenous or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for the treatment of TED. Have known autoimmune disease other than TED, that, in the opinion of the Investigator, would interfere with the course and conduct of the study. Had previous orbital irradiation or surgery for TED. Additional exclusion criteria are defined in the protocol.

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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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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Batoclimab<br>Participants will be administered batoclimab 680 mg SC weekly for 12 weeks followed by 340 mg SC weekly for 12 weeks. | Drug: Batoclimab<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Placebo Comparator: Placebo<br>Participants will be administered matching placebo SC weekly for 24 weeks. | Drug: Placebo<br>* Matching Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of proptosis responders | Proptosis is the amount of protrusion of the eye from the orbital rim. Measurements are recorded using the Hertel exophthalmometer. The study eye is defined as the most severely affected eye at the Baseline visit. Proptosis responder is defined as the participant with a greater than or equal to (≥) 2 millimeters (mm) reduction in the study eye without deterioration (≥2 mm increase) in the fellow eye. | At Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with proptosis ≥2 mm reduction and Clinical Activity Score (CAS) of less than or equal to (≤) 3 from Baseline in the study eye | The CAS measures the classical signs of acute inflammation (pain, redness, and swelling) in TED. The 7-item scale assigns 1 point for the presence of each of the parameters assessed: spontaneous retrobulbar pain, pain on attempted upward or downward gaze, redness of eyelids, redness of conjunctiva, swelling of caruncle or plica, swelling of eyelids, swelling of conjunctiva (chemosis). The sum of these points is the total score, with 0 indicating no clinical activity and 7 indicating the most severe clinical activity. Higher scores indicate worse symptoms. | Baseline and Week 24 | 
| Percentage of participants with CAS of 0 or 1 in the study eye |  | At Week 24 | 
| Mean change from Baseline in CAS in the study eye |  | Baseline and Week 24 | 
| Percentage of participants with positive binding anti-thyroid stimulating hormone receptor (TSHR) antibody (Ab) at Baseline who achieve seroconversion |  | Baseline and Week 24 | 
| Percentage of participants with decrease of at least 1 grade from Baseline in Gorman score for diplopia | Diplopia will be assessed based on 3 grades: Grade I - Intermittent diplopia (diplopia in primary position of gaze, when tired or when first awakening), Grade II - Inconstant diplopia (diplopia at extremes of gaze) and Grade III - Constant diplopia (continuous diplopia in primary or reading position). Higher scores indicate worse symptoms. | Baseline and Week 24 | 
| Mean change from Baseline in proptosis in the study eye |  | Baseline and Week 24 | 
| Percentage of participants with ≥6-point increase from Baseline in total Graves' ophthalmopathy - Quality of life (GO-QOL) score | The GO-QOL is a 16-item self-administered questionnaire designed to assess how GO affects different aspects related to quality of life (visual functioning and psychosocial consequences). The points given to questions 1 to 8 and 9 to 16 are added to obtain 2 raw scores ranging from 8 to 24; one for visual functioning and one for appearance. Higher scores indicate better outcome. | Baseline and Week 24 | 
| Percentage of participants with ≥8-degree increase from Baseline in motility (in at least 1 of 4 directions) in the study eye |  | Baseline and Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graves' Ophthalmopathy, Graves' Orbitopathy, Batoclimab, Thyroid eye disease, IMVT-1401, Monoclonal antibody, Autoimmune disorders