Thyroid Eye Disease, TED
Conditions
Brief summary
The purpose of this study is to assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of subcutaneous (SC) satralizumab, a recombinant, humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody, in participants with thyroid eye disease (TED).
Interventions
DRUGSatralizumab
Satralizumab will be administered by SC injection.
DRUGPlacebo
Placebo will be administered by SC injection
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- Clinical diagnosis of TED based on CAS
Exclusion criteria
* Decrease in CAS or proptosis of \>= 2 points or \>= 2 mm, respectively, in the study eye between Screening and Study Baseline (Day 1) * Requiring immediate surgical ophthalmological intervention or planning corrective surgery or irradiation during the course of the study, in the judgment of the investigator * Identified pre-existing ophthalmic disease that, in the judgment of the investigator, would preclude study participation or complicate interpretation of study results, including corneal decompensation unresponsive to medical management and including ophthalmic diseases that will likely require prohibited therapy during the study * Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes an individual's safe participation in and completion of the study * Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of satralizumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ≥ 2mm Reduction in Proptosis from Baseline (Day 1) at Week 24 in the Study eye | Baseline, Week 24 | Provided there is no deterioration of proptosis \[≥ 2 millimeters (mm) increase\] in the fellow eye |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Proptosis | Baseline, Week 24, Week 48 and from Week 24 to Week 48 | — |
| Percentage of Participants Achieving ≥ 1 Grade Reduction/Improvement in Diplopia Among Participants with Baseline Diplopia | Baseline, Week 24, Week 48 | — |
| Percentage of Participants Achieving Absence of Motility-induced Pain | Week 24 | — |
| Percentage of Participants Achieving Absence of Spontaneous Pain | Week 24 | — |
| Percentage of Participants with a ≥ 6 Point Improvement in the Visual Functioning and Appearance Sub-Scale Scores of the Graves Ophthalmopathy Quality of Life (GO-QoL) | Baseline, Week 24, Week 48 and from Week 24 to Week 48 | The GO-QoL is a 16-item self-administered questionnaire divided into two sub-scales and used to assess the perceived effects of TED by the participants on their: 1) Visual Functioning (questions 1-8); and 2) Appearance (questions 9-16). Both the subscales and overall score are transformed to a scale of 0 to 100. Higher total scores indicate better QoL. |
| Percentage of Participants Achieving Overall Response | Week 24. Week 48 | — |
| Percentage of Participants Achieiving ≥2 Point Reduction in Clinical Activity Score (CAS) in the Study eye | Baseline, Week 24, Week 48 | The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to TED; 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active TED (ignore "equivocal" redness); 6. Chemosis; 7. Swelling of caruncle or plica. Each item is scored as 1 (present) or 0 (absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms). Higher scores indicate worse symptoms. |
| Percentage of Participants Acheiving CAS Value of 0 or 1 in the Study eye | Week 24 | The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to TED; 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active TED (ignore "equivocal" redness); 6. Chemosis; 7. Swelling of caruncle or plica. Each item is scored as 1 (present) or 0 (absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms). Higher scores indicate worse symptoms. |
| Percentage of Participants Achieving ≥ 10 point Improvement in Ocular Surface Disease Index (OSDI) Overall Scores | Baseline, Week 24 | The OSDI instrument is a validated dry eye questionnaire and consists of three main sections concerning ocular symptoms, visual function, and environmental factors. It comprises of 12 questions and for every question, participants selects a number between 0 and 4, where 0 equals "none of the time" and 4 equals "all of the time" with totals of score ranging from 0 to 100. Higher scores represents a worse disease index. |
| Change in OSDI Ocular Symptoms and Vision-related Function Subscale Scores | Baseline, Week 24 | The OSDI instrument is a validated dry eye questionnaire and consists of three main sections concerning ocular symptoms, visual function, and environmental factors. It comprises of 12 questions and for every question, participants selects a number between 0 and 4, where 0 equals "none of the time" and 4 equals "all of the time" with totals of score ranging from 0 to 100. Higher scores represents a worse disease index. |
| Change in Oxford Corneal Staining Scores | Baseline, Week 24 | Oxford corneal staining chart consists of a 6 point scale. Staining assessment will be based on the intensity of fluorescein staining, ranging from Grade 0 to V for each panel (Grade 0-I: normal; Grade II-III: mild to moderate; Grade IV-V: severe). Higher grade indicates worse worse disease index. |
| Percentage of Participants Achieving ≥ 2mm Reduction in Proptosis at Week 48 in the Study eye | Week 48 | — |
| Percentage of Participants Requiring Surgical Intervention for TED | Up to Week 48 | — |
| Percentage of Participants With Worsening of Proptosis by ≥ 2 mm | Baseline, Week 48 and from Week 24 to Week 48 | — |
| Change in CAS | Baseline, Week 48 and from Week 24 to Week 48 | The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to TED; 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active TED (ignore "equivocal" redness); 6. Chemosis; 7. Swelling of caruncle or plica. Each item is scored as 1 (present) or 0 (absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms). Higher scores indicate worse symptoms. |
| Percentage of Participants with Adverse Events (AEs), with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5 (NCI CTCAE V5) | Baseline, Week 72 | — |
| Serum Concentration of Satralizumab | Up to Week 24 | — |
Countries
Argentina, Australia, Austria, Germany, Hong Kong, Hungary, Italy, Japan, Singapore, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed