Trial of Sibeprenlimab in the Treatment of Sjögren’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Otsuka Pharmaceutical Development & Commercialization Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

17 Sep 2025 → ongoing

Decision date (initial)

2025-04-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To compare the effect of sibeprenlimab versus placebo added to background treatment on ESSDAI at 28 weeks

Secondary objectives 9

1. To evaluate the safety and tolerability of sibeprenlimab versus placebo added to background treatment
2. To evaluate the proportion of participants with minimal clinical improvement for ESSDAI achieved with sibeprenlimab vs placebo added to background treatment at 28 weeks
3. To evaluate the proportion of participants with minimal clinical improvement for ESSPRI achieved with sibeprenlimab vs placebo added to background treatment at 28 weeks
4. To evaluate the individual domains of ESSDAI composite score after sibeprenlimab versus placebo added to background treatment at 28 weeks
5. To evaluate the salivary flow rate and tear flow rate after sibeprenlimab versus placebo added to background treatment at 28 weeks
6. To evaluate the effect of sibeprenlimab versus placebo on disease activity as measured by clinical outcome assessments at 28 weeks
7. To evaluate the effect of sibeprenlimab on PD biomarkers
8. To evaluate the PK and immunogenicity of sibeprenlimab
9. To compare the effect of sibeprenlimab versus placebo added to background treatment on ESSPRI at 28 weeks

Conditions and MedDRA coding

Treatment of Sjögren’s disease

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing. Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data. Otsuka will share data supported by the protocol, statistical analysis plan (SAP) and clinical study report (CSR) on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Signed informed consent must be obtained prior to participation in the trial
2. Participants between 18 to 75 years of age
3. Classification of Sjögren’s disease according to the 2016 American College of Rheumatology (ACR)/EULAR criteria
4. Seropositive for anti-Ro52 and/or anti-Ro60 antibodies at screening
5. Screening ESSDAI score ≥ 5; activity in the pulmonary, central nervous system, or peripheral nervous system domains will not be counted towards the qualifying screening ESSDAI score
6. Stimulated whole salivary flow rate of ≥ 0.05 mL/min at screening
7. Serum IgG > 900 mg/dL as assessed prospectively by a central laboratory test
8. Ability to communicate well with the investigator, understand and agree to comply with the requirements of the trial
9. Participants may be on hydroxychloroquine (≤ 400 mg/day), methotrexate (≤ 25 mg/week), leflunomide (≤ 20 mg daily), or azathioprine (≤ 150 mg/day) if the participant has been on a stable and well-tolerated dose for at least 30 days before randomization
10. Participants taking systemic corticosteroids have to be on a stable dose of ≤ 10 mg/day prednisone/prednisolone or equivalent for at least 30 days before randomization
11. Ability to provide written informed consent prior to initiation of any trial-specific procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial

Exclusion criteria 27

1. Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness
2. Prior use of a B-cell depleting therapy within 12 months prior to randomization; if the CD19 count has returned to the baseline value prior to receipt of the B-cell depleting therapy, or at a normal reference value, as early as 9 months since the therapy, the patient may be eligible if the B-cell count is greater than: the lower limit of normal or baseline value prior to receipt of previous B cell-depleting therapy (whichever is greater) at screening
3. Prior treatment with any of the following within 6 months prior to randomization: belimumab, abatacept, anti-tumor necrosis factor alpha biologic agents, immunoglobulins, plasmapheresis; intravenous (IV) or oral cyclophosphamide, mycophenolate mofetil, IV or oral cyclosporine A or any other immunosuppressants not specified in the protocol
4. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer
5. Any one of the following laboratory values at screening. Hematologic abnormalities below these reference values will be reviewed by the Medical Monitor and investigator to determine whether the values are attributable to Sjögren’s disease. If the abnormalities are attributable to Sjögren’s disease, the participant may be enrolled. a) Hemoglobin levels < 8.0 g/dL b) White blood cells (WBC) count < 4.0 × 103/μL c) Platelet count < 100 × 103/μL d) Absolute neutrophil count (ANC) < 1.0 × 103/μL e) eGFR calculated using the 2021 Chronic Kidney Disease-Epidemiology Collaboration serum creatinine eGFR formula < 45 mL/min/1.73 m2
6. Active viral, bacterial, or other infections requiring systemic treatment at the time of screening or randomization, or history of recurrent clinically significant infection
7. History of a previous hypersensitivity or severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis to any of the ingredients of the sibeprenlimab SC injection formulation
8. History of major organ, hematopoietic stem cell, or bone marrow transplant
9. Regular use of medications known to cause dry mouth/eyes as a regular and major side effect, and which have not been on a stable dose for at least 30 days prior to screening, or any anticipated change in the treatment regimen during the course of the trial
10. Use of topical ocular prescription medications (excluding artificial tears, gels, lubricants) that have not been on a stable dose for at least 90 days prior to randomization, or any anticipated change in the treatment regimen during the course of the trial
11. History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result
12. History of malignancy of any organ system (other than basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
13. Any history of head and neck radiation treatment
14. History of sarcoidosis
15. Presence of active fibromyalgia
16. Participant has uncontrolled type 2 diabetes, as evidenced by a screening hemoglobin A1c (HbA1c) value > 8%. Participant will be excluded if their antidiabetic regimen is not stable. A stable antidiabetic regimen is defined as either diet and exercise therapy alone or in combination with any approved antidiabetic medication in which the doses of oral or noninsulin injectable medications have not changed during the 8 weeks prior to enrollment; or the doses of long-acting insulin or intermediate-acting insulin have not varied by more than 20% during the 8 weeks prior to enrollment
17. Any surgical, medical (eg, uncontrolled hypertension, heart failure, cerebrovascular accident), psychiatric or additional physical condition that the sponsor, medical monitor, and/or investigator feels may jeopardize the participant in case of participation in this trial
18. Positive serology for hepatitis B surface antigen
19. Hepatitis C: participants with positive hepatitis C antibody and hepatitis C virus (HCV)-ribonucleic acid (RNA) at screening are excluded. Chronic hepatitis C participants who have completed HCV antiviral treatment must be HCV-RNA negative at least 12 weeks after treatment before randomization to be eligible. Cases of spontaneous HCV clearance should be discussed with the sponsor before enrollment
20. Evidence of active tuberculosis infection is exclusionary. Participant with previously treated tuberculosis and previously treated or newly diagnosed latent tuberculosis may be eligible
21. Pregnant or nursing (lactating) women
22. Participants with a known history of noncompliance to medication, or who were unable or unwilling to complete patient-reported outcome questionnaires, or who are unable or unwilling to use the device for collection of patient-reported outcomes
23. Heterosexually active biological males or participants of childbearing potential, or their partners, who do not agree to adhere to use 2 forms of highly effective contraceptives from the time of consent through the end of the participant’s participation in the trial and for an additional 90 days (biological male participants) or 30 days (biological female participants) thereafter
24. Biological male participants who do not agree to avoid donation of sperm from the time of consent through the end of the participant’s participation in the trial and an additional 90 days thereafter
25. Participant who has a recent history (ie, within the past year) of alcohol or drug/chemical abuse that would, based on the investigator’s clinical judgment, interfere with the participant’s ability to participate in the trial
26. Participant is judged by the investigator or the medical monitor to be inappropriate for the trial
27. Participants who would be likely to require prohibited concomitant therapy during the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in ESSDAI score at 28 weeks

Secondary endpoints 13

1. Change from baseline in ESSPRI score at 28 weeks
2. Incidence of TEAEs graded by severity, injection site reactions, clinical laboratory tests, vital sign measurements, and physical examinations
3. Proportion of participants with minimal clinical improvement at 28 weeks defined as ESSDAI reduction ≥ 3 points from baseline
4. Proportion of participants with minimal clinical improvement at 28 weeks defined as ESSPRI reduction ≥ 1 point from baseline
5. Change from baseline in individual ESSDAI domains at 28 weeks
6. Change from baseline at 28 weeks in the: Salivary flow rate Tear flow rate
7. Change from baseline at 28 weeks for the following: ClinESSDAI score PhGA score of disease activity PaGA score of participant outcomes FACIT-Fatigue score SF-36v2 Physical Component Summary Scale score and Mental Component Summary Scale score Patient-reported Sjögren’s disease diary score (symptom and impact)
8. Proportion of participants with minimal clinical improvement, defined as FACIT-Fatigue score increase of ≥ 4 from baseline, at 28 weeks
9. Time to the first occurrence of minimal clinical improvement in ESSDAI by Week 28
10. Time to the first occurrence of minimal clinical improvement in ESSPRI by Week 28
11. Percent change from baseline to Week 28 in total serum IgA, IgG, IgM, and free APRIL concentrations
12. Evaluation of PK profile
13. Evaluation of serum ADA

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Otsuka Pharmaceutical Development & Commercialization Inc.

Sponsor organisation

Otsuka Pharmaceutical Development & Commercialization Inc.

Address

2440 Research Boulevard

City

Rockville

Postcode

20850-3238

Country

United States

Scientific contact point

Organisation

Otsuka Pharmaceutical Development & Commercialization Inc.

Contact name

EU Clinical Trials Helpdesk

Public contact point

Organisation

Otsuka Pharmaceutical Development & Commercialization Inc.

Contact name

EU Clinical Trials Helpdesk

Third parties 17

Locations

6 EU/EEA countries · 37 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 104 files

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

Application history

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