A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy and Safety of Abiprubart in Participants with Sjögren’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kiniksa Pharmaceuticals GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11], Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Immune System Diseases [C20], Diseases [C] - Stomatognathic Diseases [C07]

Trial duration

completed 1 May 2025

Decision date (initial)

2024-12-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Kiniksa Pharmaceuticals, GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Efficacy, Safety, Pharmacokinetic

To evaluate the effect of abiprubart on an established systemic disease activity measure for Sjögren’s Disease

Secondary objectives 4

1. To evaluate the effect of abiprubart on established disease symptom and outcome measures for Sjögren’s Disease
2. To evaluate the effect of abiprubart on glandular function symptoms, and systemic disease activity measures for Sjögren’s Disease
3. To evaluate the effect of abiprubart on functional status and health-related quality of life of patients with Sjögren’s Disease
4. To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of abiprubart on Sjögren’s Disease

Conditions and MedDRA coding

Sjögren’s Disease

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. Is capable of understanding the written ICF, has provided signed written informed consent, and agrees to comply with protocol requirements.
2. 10. If female, must be either postmenopausal (defined as no menses for 12 months without other medical cause), permanently surgically sterile (i.e., removal of ovaries, fallopian tubes, and/or uterus), or, for women of childbearing potential, must: a. Be nonpregnant, nonlactating, and agree to remain abstinent or use a method of contraception with a failure rate of < 1% per year from the screening visit until after the EOS visit. Examples of contraception methods with a failure rate of < 1% per year include: i. hormonal contraceptives associated with inhibition of ovulation (stable dose for at least 4 weeks prior to first dose of study drug); hormonal contraceptive methods must be supplemented by a barrier method ii. hormone-releasing or copper intrauterine device iii. bilateral tubal occlusion iv. vasectomized male partner v. abstinence from heterosexual intercourse; the reliability of sexual abstinence should be evaluated based on duration of the study and usual lifestyle of the participant. Intermittent abstinence (such as calendar, ovulation, symptothermal or postovulation) and withdrawal are not considered acceptable contraceptive methods b. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations
3. 11. Sexually active male participants must have documented vasectomy or must agree to use a condom or method of contraception with a failure rate of <1% per year, as defined above with their partners of childbearing potential from first dose of study drug until after the EOS visit.
4. 12. Male participants must agree to refrain from donating sperm from first dose of study drug until 30 days after the last study drug administration. Female participants must agree to refrain from donating eggs from first dose of study drug until after the EOS visit.
5. 13. Females of childbearing potential must have a negative serum β-human chorionic gonadotropin test during screening and negative urine pregnancy test on Day 1.
6. 2. Is male or female at birth, and > 18 years of age and < 81 years of age at Screening.
7. 3. Has a diagnosis of Sjögren’s Disease according to 2016 ACR-EULAR Classification Criteria.
8. 4. Has ESSDAI value ≥ 5, counting only the biological, hematological, articular, cutaneous, glandular, lymphadenopathy, and constitutional organ domains at Screening.
9. 5. Is seropositive at Screening for anti-SSA antibodies tested at a central laboratory.
10. 6. Has stimulated whole salivary flow rate at Screening of ≥ 0.05 mL/min.
11. 7. Weighs at least 40 kg and no more than 150 kg and has a body mass index (BMI) within the range of 18-40 kg/m2.
12. 8. Routine adult vaccinations, including COVID-19, influenza, pneumonia, and zoster, should be up to date and/or vaccines offered at least 2 weeks prior to randomization according to regional and national guidelines based on medical history or presence of risk factors, in the opinion of the Investigator.
13. 9. [Original Criterion deleted]
14. A full list of inclusion criteria can be found in the current protocol.

Exclusion criteria 14

1. 1. Prior exposure to any other anti-CD40/CD154 agent.
2. 10. Has received immunization with a live (attenuated) vaccine within 4 weeks prior to randomization or is expected to receive live (attenuated) vaccine during the study or within 6 weeks after the last study drug administration.
3. 11. Positive or indeterminate results for hepatitis C virus infection or chronic active hepatitis B infection (at Screening) as defined below: a. Hepatitis C antibody positive b. Hepatitis B surface antigen positive c. Hepatitis B anti-core antibody positive but anti-surface antibody negative
4. 12. History of thromboembolic event or a significant risk of future thromboembolic events (defined as a definitive diagnosis of thrombophilia OR an ongoing condition associated with an increased incidence of intravascular thrombosis, such as atrial fibrillation or anti-phospholipid syndrome). All history of intravascular thrombosis should be approved by the medical monitor.
5. 13. Has any prior history of lymphoid malignancy associated with Sjögren’s Disease diagnosis.
6. 2. Diagnosis of Sjögren’s Disease overlap syndromes where another autoimmune rheumatic disease constitutes the principal illness, including fibromyalgia with currently active, inadequately controlled symptoms.
7. 3. Is currently enrolled in another clinical study (at the time of Screening), with the exception of observational studies.
8. 4. Concurrent or prior disease modifying treatments prior to study treatment period defined in the table within protocol section 4.2
9. 5. Has received cataract surgery, Lasik, or other ophthalmologic surgery procedure (e.g., lachrymal plug) in the 6 months prior to Screening.
10. 6. Injectable corticosteroids (including intra-articular) within 8 weeks prior to randomization. (Note: Concomitant-treatment with nonsteroidal anti-inflammatory drugs, acetaminophen, oral corticosteroids [equivalent to prednisone ≤ 10 mg/day], or inhaled corticosteroids at a stable dose ≥ 4 weeks prior to baseline for stable medical conditions is allowed and should be kept at a stable dose throughout the study).
11. 7. Has started, stopped or adjusted dose/regimen of medications for treatment of, or known to cause, dry mouth/eyes (such as sialagogues, artificial saliva, artificial tears, other topical ophthalmologic agents, antihistamines, antidepressants, anticholinergics, sedatives, antipsychotic drugs, or anti-Parkinson agents), within the 30 days prior to screening or is anticipating change to these treatment regimens during the study.
12. 8. Has history of immunodeficiency (e.g., immune disorders or disorders that result in decreased immunity), including human immunodeficiency virus (HIV). HIV test will be performed during screening unless participant has a previously documented negative HIV result within 8 weeks prior to Screening.
13. 9. Positive (or 2 indeterminate) QuantiFERON® test results unless confirmation of prior completion of appropriate treatment for latent TB and no evidence of active TB – QuantiFERON TB-Gold (QFT) testing should be performed through the central laboratory. QFT testing may be performed by a local laboratory with approval from the medical monitor. QFT test will be performed during screening unless participant has a previously documented negative QFT result within 8 weeks prior to Screening or documented prior positive QFT at any time. – An indeterminate QFT test should be repeated. – A positive QFT test or two successive indeterminate QFT results should be considered a positive diagnostic TB test. – An indeterminate QFT test followed by a negative QFT test should be considered a negative diagnostic TB test. – When possible, QFT test should be performed at least 4 weeks after receiving an mRNA COVID-19 vaccine.
14. A full list of exclusion criteria can be found in the current protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in European League Against Rheumatism (EULAR) Sjögren’s Disease Activity Index (ESSDAI) at Week 24 (Change from baseline of individual ESSDAI domains will also be reported as supportive information.)

Secondary endpoints 15

1. Proportion of Sjögren’s Tool for Assessing Response (STAR) responders (≥ 5 points) at Week 24 and evaluation of the individual STAR domains
2. Change from baseline in ESSDAI over time
3. Proportion of STAR responders (≥ 5 points) over time
4. Change from baseline in Stimulated Salivary Flow at Week 24 and over time
5. Change from baseline in Unstimulated Salivary Flow at Week 24 and over time
6. Change from baseline in ESSPRI at Week 24 and over time
7. Change from baseline in Schirmer’s test at Week 24 and over time
8. Change from baseline in clinESSDAI at Week 24 and over time
9. Change from baseline in FACIT-Fatigue at Week 24 and over time
10. Change from baseline in EQ-5D 5L at Week 24 and over time
11. Incidence of treatment-emergent adverse events (TEAEs), and serious AEs (SAEs)
12. Clinically significant laboratory or electrocardiogram (ECG) changes
13. Abiprubart serum concentrations over time, and PK parameters
14. Antidrug antibodies
15. Receptor occupancy (RO, US clinical sites only)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kiniksa Pharmaceuticals GmbH

Sponsor organisation

Kiniksa Pharmaceuticals GmbH

Address

Grafenaustrasse 5

City

Zug

Postcode

6300

Country

Switzerland

Scientific contact point

Organisation

Kiniksa Pharmaceuticals GmbH

Contact name

Eric Jenkins

Public contact point

Organisation

Kiniksa Pharmaceuticals GmbH

Contact name

Rachel Frank

Third parties 4

Locations

6 EU/EEA countries · 35 investigational sites

By country

Investigational sites

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 85 files

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

Application history

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