A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Participants with Moderate-to-Severe Thyroid Eye Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11], Diseases [C] - Immune System Diseases [C20]

Trial duration

27 Dec 2023 → ongoing

Decision date (initial)

2023-10-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

F. Hoffmann La Roche

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacodynamic

To evaluate the efficacy of subcutaneous satralizumab compared with placebo at Week 24 based on proptosis response

Secondary objectives 8

1. To evaluate the efficacy of subcutaneous satralizumab compared with placebo at Week 24 based on overall response
2. To assess the efficacy of subcutaneous satralizumab compared with placebo at Week 24 based on reduction in the clinical activity score
3. To assess the efficacy of subcutaneous satralizumab compared with placebo based on change in proptosis from baseline to Week 24
4. To assess the efficacy of subcutaneous satralizumab compared with placebo at Week 24 based on health-related quality of life (Graves’ Ophthalmopathy Quality of Life Questionnaire)
5. To assess the efficacy of subcutaneous satralizumab compared with placebo at Week 24 based on reduction/improvement in diplopia
6. To assess the efficacy of subcutaneous satralizumab compared with placebo at Week 24 based on improvement in orbital pain
7. To evaluate the safety and tolerability of satralizumab
8. To characterize the satralizumab pharmacokinetic (PK) profile

Conditions and MedDRA coding

Moderate-to-Severe Thyroid Eye Disease

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001625-PIP05-23

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age >=18 years at the time of signing Informed Consent Form
2. FOR ACTIVE TED PATIENTS: Clinical diagnosis of active thyroid eye disease (TED) with clinical activity score (CAS) >= 3 (on the 7 item scale) at screening and baseline (Day 1) in the study eye  FOR CHRONIC INACTIVE TED PATIENTS: Clinical diagnosis of stable, chronic (inactive) TED, as determined by participant medical records indicating CAS < 3 (on a 7-item scale) in both eyes for at least 6 months prior to screening, or all of the following: o No progression in proptosis for at least 6 months prior to screening o If participant has a history of diplopia due to TED, no progression in diplopia for at least 6 months prior to screening o No new inflammatory TED symptoms for at least 6 months prior to screening.
3. FOR ACTIVE TED PATIENTS: Diagnosis of active moderate-to-severe TED; usually associated with proptosis (exophthalmos) >= 3 mm above normal for race and gender in the study eye. Additionally, participants must have one or more of the following: lid retraction >=2 mm, moderate or severe soft tissue involvement, and/or inconstant or constant diplopia.  FOR CHRONIC INACTIVE TED PATIENTS: History and presence at screening and baseline of chronic TED as estimated by treating physician with proptosis (exophthalmos) >= 3 mm above normal for race and gender in the study eye. Additionally, participants must have one or more of the following: lid retraction >=2 mm, moderate or severe soft tissue involvement, and/or inconstant or constant diplopia.
4. FOR ACTIVE TED PATIENTS: Onset of active TED symptoms in the study eye (as determined by participant medical records) <= 12 months prior to baseline (Day 1)  FOR CHRONIC INACTIVE TED PATIENTS: Initial TED diagnosis >12 months but < 10 years prior to screening
5. Euthyroid with the background disease under control, or have mild hypo or hyperthyroidism
6. FOR CHRONIC INACTIVE TED PATIENTS: CAS <3 (on a 7-item scale) in both eyes at screening and baseline (Day 1) visits

Exclusion criteria 6

1. Decrease in CAS or proptosis of >= 2 points or >= 2 mm, respectively, in the study eye between Screening and Baseline visit (Day 1)
2. Requiring immediate surgical ophthalmological intervention or planning corrective surgery or irradiation during the course of the study, in the judgment of the investigator
3. 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
4. FOR ACTIVE TED: Any prior CS use (IV or oral) with a cumulative dose equivalent to >= 1 g of methylprednisolone or equivalent for the treatment of any condition within 3 months prior to screening. FOR CHRONIC INACTIVE TED: Use of any CSs (periocular, IV, oral, IVT injections or implants) for any indication within 3 weeks prior to screening.
5. 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
6. Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of satralizumab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants (with active disease) achieving >= 2mm reduction in proptosis from baseline (Day 1) at Week 24 in the study eye, provided there is no deterioration of proptosis (>= 2mm increase) in fellow eye

Secondary endpoints 16

1. 1. Proportion of participants with active disease achieving overall response at Week 24, defined as a >= 2-point reduction in CAS, AND a >= 2 mm reduction in proptosis from baseline (Day 1) in the study eye, provided there is no corresponding deterioration in CAS or proptosis (>= 2 point/mm increase) in the fellow eye
2. 2. Proportion of participants (with active and chronic inactive disease) achieving >= 2 mm reduction in proptosis from baseline (Day 1) at Week 24 in the study eye provided there is no corresponding deterioration in proptosis (>= 2 mm increase) in the fellow eye
3. 3. Proportion of participants with active disease achieving a >= 2-point reduction in CAS from baseline (Day 1) to Week 24
4. 4. Change from baseline (Day 1) in proptosis at Week 24 in participants with active disease
5. 5. Change from baseline (Day 1) in proptosis at Week 24 in participants with active and chronic inactive disease
6. 6. Proportion of participants with active disease with a >= 6 point improvement in the Visual Functioning and Appearance sub-scale scores of the Grave’s orbitopathy- Quality of Life (GO-QoL) questionnaire from baseline at Week 24
7. 7. Proportion of participants with active and chronic inactive disease with a >= 6 point improvement in the Visual Functioning and Appearance sub- scale scores of the Grave’s orbitopathy- Quality of Life (GO-QoL) questionnaire from baseline from week 24 at Week 48
8. 8. Proportion of participants with active disease achieving >= 1 grade reduction/improvement in diplopia at Week 24 among participants with baseline diplopia
9. 9. Proportion of participants with active and chronic inactive disease achieving >= 1 grade reduction/improvement in diplopia at Week 24 among participants with baseline diplopia
10. 10. Proportion of participants with active disease achieving absence of motility-induced pain at Week 24 among participants with motilityinduced pain at baseline
11. 11. Proportion of participants with active disease achieving absence of spontaneous pain at Week 24 among participants with spontaneous pain at baseline
12. 12. Proportion of participants with a >= 6-point improvement in the Visual Functioning and Appearance sub-scale scores of the GO-QoL from baseline (Day 1) to Week 48
13. 13 . Incidence, seriousness, and severity of adverse events (AEs), with severity determined according to National cancer institute common terminology criteria for adverse events version 5 (NCI CTCAE V5)
14. 14 . Change from baseline (Day 1) in vital signs, targeted clinical laboratory test results, electrocardiogram (ECG) parameters, and body weight
15. 15 . Serum concentration of satralizumab at specified timepoints
16. 16 . Estimates of primary PK parameters (e.g., CL/F and V/F) and secondary PK parameters (e.g., AUC) derived using popPK modeling

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 5

Locations

4 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 58 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications