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A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Participants With Thyroid Eye Disease

Phase 3
Active, not recruiting
Conditions
Thyroid Eye Disease
Interventions
Drug: Placebo
Registration Number
NCT06106828
Lead Sponsor
Hoffmann-La Roche
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
127
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SatralizumabSatralizumabIn the Part I period, participants will receive satralizumab every 4 weeks (q4w) followed by proptosis response-based individualized treatment in Part II of the study.
PlaceboPlaceboIn the part I period, participants will receive placebo q4w followed by proptosis response-based individualized treatment in part II of the study.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving ≥ 2 millimetres (mm) Reduction in Proptosis From Baseline (Day 1) at Week 24 in the Study EyeBaseline, Week 24

Provided there is no deterioration of proptosis (≥ 2mm increase) in the fellow eye.

Secondary Outcome Measures
NameTimeMethod
Change in ProptosisBaseline, 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 DiplopiaBaseline, Week 24, and Week 48
Percentage of Participants Achieving Absence of Motility-induced PainWeek 24
Percentage of Participants Achieving Absence of Spontaneous PainWeek 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 ResponseWeek 24, Week 48
Percentage of Participants Achieving a ≥ 2 Point Reduction in Clinical Activity Score (CAS) in the Study EyeBaseline, Week 24, and 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 Achieving CAS Value of 0 or 1 in the Study eyeWeek 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 ScoresBaseline, Week 24

The OSDI instrument is a validated dry eye questionnaire, designed to assess cornea and ocular surface symptoms. It comprises of 12 questions with three main sections concerning ocular symptoms, visual function, and environmental factors. For each 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 ranging from 0 to 100. Higher score indicates worse disease index.

Change in OSDI Ocular Symptoms and Vision-related Function Subscale ScoresBaseline, Week 24

The OSDI instrument is a validated dry eye questionnaire, designed to assess cornea and ocular surface symptoms. It comprises of 12 questions with three main sections concerning ocular symptoms, visual function, and environmental factors. For each 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 ranging from 0 to 100. Higher score indicates worse disease index.

Change in Oxford Corneal Staining ScoresBaseline, 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 disease index.

Percentage of Participants Achieving ≥ 2mm Reduction in Proptosis at Week 48 in the Study eyeWeek 48
Percentage of Participants Requiring Surgical Intervention for TEDUp to Week 48
Percentage of Participants With Worsening of Proptosis by ≥ 2 mmBaseline, Week 48 and from Week 24 to Week 48
Change in CASBaseline, Week 48 and from Week 24 to Week 48
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 up to Week 72
Serum Concentration of SatralizumabUp to Week 24

Trial Locations

Locations (41)

Retina Consultants of Texas

🇺🇸

San Antonio, Texas, United States

University of Alberta

🇨🇦

Edmonton, Alberta, Canada

Toronto Retina Institute

🇨🇦

Toronto, Ontario, Canada

Universite de Montreal - Hopital Maisonneuve-Rosemont

🇨🇦

Montreal, Quebec, Canada

Peking Union Medical College Hospital

🇨🇳

Beijing City, China

CHNO Hopital des Quinze Vingts

🇫🇷

Paris, France

Fondation Rothschild

🇫🇷

Paris, France

Hospital Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Universitario Clínico San Carlos

🇪🇸

Madrid, Spain

Plastics-Orbit-Neuro

🇺🇸

San Diego, California, United States

Connecticut Eye Consultants, P.C.

🇺🇸

Danbury, Connecticut, United States

University of Illinois Eye and Ear Infirmary

🇺🇸

Chicago, Illinois, United States

Scheie Eye Institute

🇺🇸

Philadelphia, Pennsylvania, United States

Vanderbilt Eye Institute

🇺🇸

Nashville, Tennessee, United States

CHU Nantes - Hôtel Dieu

🇫🇷

Nantes, France

Peking University Third Hospital

🇨🇳

Beijing, China

Beijing Hospital of Ministry of Health

🇨🇳

Beijing, China

Beijing Tongren Hospital, Capital Medical University

🇨🇳

Beijing, China

Xi'an Fourth Hospital

🇨🇳

Xi'an City, China

Hadassah MC

🇮🇱

Jerusalem, Israel

Rabin MC

🇮🇱

Petach Tikva, Israel

Sheba medical center

🇮🇱

Ramat Gan, Israel

Seoul National University Bundang Hospital

🇰🇷

Seongnam-si, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Chung-Ang University Hospital

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Specjalistyczny O?rodek Okulistyczny Oculomedica

🇵🇱

Bydgoszcz, Poland

Optimum Profesorskie Centrum Okulistyki

🇵🇱

Gdansk, Poland

AIBILI - Association for Innovation and Biomedical Research on Light

🇵🇹

Coimbra, Portugal

Hospital Universitari de Bellvitge

🇪🇸

Hospitalet De Llobregat, Barcelona, Spain

Hospital Universitario Vall d Hebron

🇪🇸

Barcelona, Spain

Hospital Universitario Virgen de las Nieves

🇪🇸

Granada, Spain

Hospital Universitario Virgen de la Macarena

🇪🇸

Sevilla, Spain

Hospital Universitario la Fe: Servicio de Oftalmologia

🇪🇸

Valencia, Spain

Sussex Eye Hospital

🇬🇧

Brighton, United Kingdom

Bristol Eye Hospital

🇬🇧

Bristol, United Kingdom

Gartnavel General Hospital

🇬🇧

Glasgow, United Kingdom

St James University Hospital

🇬🇧

Leeds, United Kingdom

Royal Liverpool University Hospital

🇬🇧

Liverpool, United Kingdom

Moorfields Eye Hospital NHS Foundation Trust

🇬🇧

London, United Kingdom

Maidstone Hospital

🇬🇧

Maidstone, Kent, United Kingdom

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