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 in the Active TED Population Who Achieved ≥ 2 Millimeters (mm) Reduction in Proptosis From Baseline at Week 24 in the Study Eye | At Week 24 | Percentage of participants in the active TED population (i.e., participants who have active disease) who achieved a ≥ 2 mm reduction in proptosis from baseline (Day 1) to Week 24 in the study eye, with no corresponding deterioration of proptosis (≥ 2 mm increase) in the fellow eye has been reported. Percentages have been rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in the Overall Population Who Achieved ≥ 2 mm Reduction in Proptosis From Baseline at Week 24 in the Study Eye | At Week 24 | Percentage of participants in the overall population (i.e., participants with active and chronic inactive TED) who achieved a ≥ 2 mm reduction in proptosis from baseline (Day 1) to Week 24 in the study eye, with no corresponding deterioration of proptosis (≥ 2 mm increase) in the fellow eye has been reported. Percentages have been rounded off. |
| Change From Baseline in Proptosis at Week 24 in Active TED Population for Study Eye | At Week 24 | — |
| Change From Baseline in Proptosis at Week 24 in Overall Population for Study Eye | At Week 24 | — |
| Percentage of Participants in Active TED Population Achieving ≥ 1 Grade Reduction/Improvement in Diplopia at Week 24 | At Week 24 | Diplopia grade was assessed with the use of the Gorman subjective diplopia score (range: 0-3 points), which included: no diplopia (absent, scored as 0), diplopia in the primary position of gaze when the participant is tired or awakening (intermittent, scored as 1), diplopia at extremes of gaze (inconstant, scored as 2), and continuous diplopia in the primary or reading position (constant, scored as 3). Participants with active TED with diplopia present at baseline who had Grade ≥1 reduction or improvement at Week 24 have been reported. Percentages have been rounded off. |
| Percentage of Participants in the Overall Population Achieving ≥ 1 Grade Reduction/Improvement in Diplopia at Week 24 | At Week 24 | Diplopia grade was assessed with the use of the Gorman subjective diplopia score (range: 0-3 points), which included: no diplopia (absent, scored as 0), diplopia in the primary position of gaze when the participant is tired or awakening (intermittent, scored as 1), diplopia at extremes of gaze (inconstant, scored as 2), and continuous diplopia in the primary or reading position (constant, scored as 3). Participants with active and chronic inactive TED with diplopia present at baseline who had Grade ≥1 reduction or improvement at Week 24 have been reported. Percentages have been rounded off. |
| Percentage of Participants in Active TED Population Achieving Absence of Motility-induced Pain at Week 24 | At Week 24 | Percentages have been rounded off. |
| Percentage of Participants Active TED Population Achieving Absence of Spontaneous Pain at Week 24 | At Week 24 | Percentages have been rounded off. |
| Percentage of Participants in Active TED Population With a ≥ 6-point Improvement in the Visual Functioning Subscale of the Graves' Ophthalmopathy Quality of Life (GO-QoL) From Baseline at Week 24 | At Week 24 | 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 subscales and overall score (sum of scores from all 16 questions) are transformed to a scale of 0 to 100. Higher total scores indicate better QoL. Percentages have been rounded off. |
| Percentage of Participants in Active TED Population With a ≥6-point Improvement in the Appearance Subscale of the GO-QoL From Baseline at Week 24 | At Week 24 | 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 subscales and overall score (sum of scores from all 16 questions) are transformed to a scale of 0 to 100. Higher total scores indicate better QoL. Percentages have been rounded off. |
| Percentage of Participants in Active TED Population Who Achieved Overall Response in the Study Eye at Week 24 | At Week 24 | Overall Response was defined as a ≥ 2-point reduction in clinical activity score (CAS), and a ≥ 2 mm reduction in proptosis from baseline in the study eye, provided there is no corresponding deterioration in CAS or proptosis (≥ 2-point/mm increase) in the fellow eye. 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. Percentages have been rounded off. |
| Percentage of Participants in Active TED Population Who Achieved a ≥ 2-point Reduction in CAS in the Study Eye From Baseline to Week 24 | At Week 24 | 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. Percentages have been rounded off. |
| Percentage of Participants in Active TED Population Who Achieved a CAS Value of 0 or 1 in the Study Eye at Week 24 | At Week 24 | 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. Percentages have been rounded off. |
| Percentage of Participants With a ≥10-point Improvement in the Ocular Surface Disease Index (OSDI) Overall Scores Across All Levels of Baseline Severity at Week 24 in Overall Population | At 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 select 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 represent a worse disease index. Percentages have been rounded off. |
| Change From Baseline in the OSDI Ocular Symptoms, and Vision-related Function Subscale Scores at Week 24 in the Overall Population | At 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 select 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 represent a worse disease index. |
| Change From Baseline in Oxford Corneal Staining Scores at Week 24 in the Overall Population | At Week 24 | Corneal staining was graded using Oxford Corneal Staining Chart which 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 (0=absent; I=minimal; II=mild; III=moderate; IV= marked; and V=severe). Higher grade indicates worse disease index. The observer compares the overall appearance of the participant's corneal staining with the reference figure in the protocol. The observer selects the appropriate grade that best represents the state of corneal staining. The staining score were recorded for the exposed interpalpebral cornea and conjunctiva. |
| Percentage of Participants Who Achieved Complete Binocular Diplopia Response at Week 24 in Overall Population | At Week 24 | The percentage of participants achieving a complete binocular diplopia response (diplopia score=0) at Week 24 have been reported. Diplopia grade was assessed with the use of the Gorman subjective diplopia score (range: 0-3 points), which included: no diplopia (absent, scored as 0), diplopia in the primary position of gaze when the participant is tired or awakening (intermittent, scored as 1), diplopia at extremes of gaze (inconstant, scored as 2), and continuous diplopia in the primary or reading position (constant, scored as 3). |
| Percentage of Participants Achieving ≥2 mm Reduction in Proptosis at Week 48 in the Study Eye | At Week 48 | Percentage of participants who will achieve a ≥ 2 mm reduction in proptosis from baseline (Day 1) to Week 48 in the study eye, with no corresponding deterioration of proptosis (≥ 2 mm increase) in the fellow eye will be reported. |
| Percentage of Participants Achieving Overall Response at Week 48 | At Week 48 | Overall Response is defined as a ≥ 2-point reduction in CAS, and a ≥ 2 mm reduction in proptosis from baseline in the study eye, provided there is no corresponding deterioration in CAS or proptosis ( ≥ 2-point/mm increase) in the fellow eye. 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 a ≥ 2-point Reduction in CAS in the Study Eye From Baseline at Week 48 | At 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 Grade ≥ 1 Reduction/Improvement in Diplopia at Week 48 in Participants With Baseline Diplopia > 0 | At Week 48 | Diplopia grade was assessed with the use of the Gorman subjective diplopia score (range: 0-3 points), which included: no diplopia (absent, scored as 0), diplopia in the primary position of gaze when the participant is tired or awakening (intermittent, scored as 1), diplopia at extremes of gaze (inconstant, scored as 2), and continuous diplopia in the primary or reading position (constant, scored as 3). |
| Percentage of Participants With a ≥ 6-point Improvement in the Visual Functioning and Appearance Subscale Scores of the GO-QoL at Week 48 | At 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 subscales and overall score (sum of scores from all 16 questions) are transformed to a scale of 0 to 100. Higher total scores indicate better QoL. |
| Change From Baseline in Proptosis at Week 48 | At Week 48 | — |
| Percentage of Participants Requiring Surgical Intervention for TED up to Week 48 | Up to Week 48 | — |
| Percentage of Participants With Worsening of Proptosis by ≥ 2 mm From Week 24 to Week 48 | From Week 24 to Week 48 | — |
| Percentage of Participants With Worsening of Proptosis by ≥ 2 mm From Baseline to Week 48 | From Baseline to Week 48 | — |
| Percentage of Participants With Maintenance of Proptosis Response From Week 24 at Week 48 | Week 24, Week 48 | — |
| Percentage of Participants With Maintenance of CAS Response From Week 24 at Week 48 | 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 With Maintenance of Proptosis Response From Baseline at Week 48 | At Week 48 | — |
| Percentage of Participants With Maintenance of CAS Response From Baseline at Week 48 | At 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. |
| Change in Proptosis From Week 24 to 48 | From Week 24 to Week 48 | — |
| Change in CAS From Week 24 to 48 | 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 a ≥6-point Improvement in the Visual Functioning and Appearance Subscale Score of the GO-QoL From Week 24 at Week 48 | Week 24, 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 subscales and overall score (sum of scores from all 16 questions) are transformed to a scale of 0 to 100. Higher total scores indicate better QoL. |
| Change From Baseline in Proptosis to Week 48 | Baseline up to Week 48 | — |
| Change From Baseline in CAS to Week 48 | Baseline up 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. |
| Number of Participants With Adverse Events (AEs) | Up to Week 72 | An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. |
| Serum Trough Concentration (Ctrough) of Satralizumab at Specified Timepoints | Baseline, Weeks 2, 4, 8, 12 and 24 | — |
| Number of Participants With Anti-drug Antibody to Satralizumab at Baseline and During the Study | Up to Week 48 | — |
Countries
Argentina, Australia, Austria, Germany, Hong Kong, Hungary, Italy, Japan, Singapore, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 131 participants with moderate-to-severe active and chronic inactive thyroid eye disease (TED) took part in the study at 45 investigative sites across 10 countries. Data up to the primary clinical cut-off date (CCOD) have been presented here. Participant flow will be updated 1 year after the study completion date.
Pre-assignment details
Participants were randomized in a 1:1 ratio to receive either subcutaneous (SC) satralizumab or a matching placebo in Part I (Weeks 1-24). After Part I analysis, proptosis responders were re-randomized to satralizumab or placebo, and proptosis non-responders received satralizumab in Part II. The data for Part II will be presented 1 year after the study completion date.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 33 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 82 Participants |
| Sex: Female, Male Female | 92 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 62 |
| other Total, other adverse events | 13 / 67 | 15 / 62 |
| serious Total, serious adverse events | 3 / 67 | 2 / 62 |
Outcome results
None listed