Abiprubart for Sjögren's Syndrome

No longer recruiting at 15 trial locations

Overseen By Clinical Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kiniksa Pharmaceuticals International, plc

Must not be taking: Injectable corticosteroids

Disqualifiers: Fibromyalgia, Immunodeficiency, Thromboembolic, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called abiprubart for individuals with Sjögren's Syndrome, a condition causing dry mouth, dry eyes, and joint pain. The main goal is to evaluate how effectively abiprubart reduces symptoms. Participants will receive either abiprubart or a placebo (a substance with no active medication) to compare effects. Those diagnosed with Sjögren's and experiencing symptoms like dry mouth or eyes might be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot change medications for dry mouth/eyes within 30 days before the trial or during it. Injectable corticosteroids must be stopped 8 weeks before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abiprubart has been well tolerated in past studies. In one study involving individuals with rheumatoid arthritis, abiprubart did not cause any major safety issues. Participants experienced no serious side effects, and their regular health checks, such as lab tests and vital signs, remained normal. Another study found that patients who did not respond to other treatments also tolerated abiprubart well. These results suggest that abiprubart is generally safe. However, discussing possible risks with the study team is important before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike current treatments for Sjögren's Syndrome, which often focus on symptom management, Abiprubart is designed to target the root cause of the disease by modulating the immune system. This treatment works by using a novel mechanism to specifically inhibit the action of certain immune cells that contribute to the inflammation and damage in Sjögren's. Researchers are particularly excited about Abiprubart's potential to provide a more targeted and effective approach, potentially reducing the need for systemic treatments like steroids or immunosuppressants, which can have significant side effects. Additionally, the subcutaneous delivery of Abiprubart, administered every two to four weeks, offers a convenient option compared to more frequent dosing schedules of some current therapies.

What evidence suggests that abiprubart could be an effective treatment for Sjögren's Syndrome?

Research has shown that abiprubart might help treat Sjögren's Syndrome. This treatment blocks a protein called CD40, which influences the immune system's response that can cause inflammation. Early findings suggest that abiprubart reduces symptoms in conditions like rheumatoid arthritis, which is somewhat similar to Sjögren's Syndrome. In past studies, patients taking abiprubart improved more than those taking a placebo. In this trial, participants will receive either abiprubart or a placebo. Most people tolerated the treatment well, experiencing no serious side effects. Overall, these early results are promising for its potential use in Sjögren's Syndrome. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with Sjögren's Disease, a condition where the immune system attacks glands that make tears and saliva. The eligibility criteria are not fully listed here, but typically include having a diagnosis of Sjögren's Syndrome and meeting certain health standards.

Inclusion Criteria

Has stimulated whole salivary flow rate at Screening of ≥ 0.05 mL/min

I tested positive for SSA antibodies.

I have been diagnosed with Sjögren's Disease.

Exclusion Criteria

Has history of immunodeficiency, including human immunodeficiency virus (HIV)

I have been treated with a drug targeting CD40 or CD154 before.

My main illness is an autoimmune disease, not just Sjögren's, and includes uncontrolled fibromyalgia symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Double-blind Treatment

Participants receive either abiprubart or placebo in a double-blind manner for 24 weeks

24 weeks

Bi-weekly visits for subcutaneous injections

Active Treatment

Participants receive active abiprubart treatment for an additional 24 weeks

24 weeks

Bi-weekly or monthly visits for subcutaneous injections

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abiprubart

Trial Overview The study aims to test the effectiveness and safety of Abiprubart compared to a placebo in managing Sjögren's Disease. Participants will be randomly assigned to receive either Abiprubart or an inactive substance (placebo).

How Is the Trial Designed?

Group I: Abiprubart 400mg SC q4wk Experimental Treatment 2 Interventions

Part A: Loading dose of abiprubart 800 mg SC followed by abiprubart 400 mg SC q2wk through Week 22 which will alternately administer placebo or abiprubart to provide active drug every 4 weeks (q4wk) while maintaining treatment concealment. Part B: Abiprubart 400 mg SC q4wk: abiprubart 400 mg SC q2wk up to and including Week 46 which will alternately administer placebo or abiprubart to provide active drug q4wk while maintaining treatment concealment.

Group II: Abiprubart 400mg SC q2wk Experimental Treatment 1 Intervention

Part A: Loading dose of abiprubart 800 mg subcutaneous (SC) followed by abiprubart 400 mg SC every 2 weeks (q2wk) through Week 22. Part B: Abiprubart 400 mg SC q2wk: abiprubart 400 mg SC q2wk up to and including Week 46.

Group III: Placebo Placebo Group 2 Interventions

Part A: A matched volume placebo loading dose followed by placebo SC injections q2wk through Week 22. Part B: Participants assigned to placebo in Part A will transition to active abiprubart treatment, according to randomized assignment, with either abiprubart 400 mg SC q2wk or abiprubart 400 mg SC q4wk.

Who Is Running the Clinical Trial?

Kiniksa Pharmaceuticals International, plc

Lead Sponsor

Trials

3

Recruited

1,500+

Kiniksa Pharmaceuticals, GmbH

Industry Sponsor

Trials

1

Recruited

200+

Published Research Related to This Trial

Oral pilocarpine significantly improved subjective symptoms and objective measures of dry eye in patients with Sjögren syndrome after 1 and 3 months of treatment, indicating its efficacy for severe cases unresponsive to standard treatments.

The study supports the safety of oral pilocarpine as a new treatment option for severe dry eye, although it did not show significant improvement in tear production as measured by Schirmer I testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Oral Pilocarpine in Treating Severe Dry Eye in Patients With Sjögren Syndrome. Kawakita, T., Shimmura, S., Tsubota, K.[2017]

In a phase II trial involving 42 patients with primary Sjögren's syndrome, telitacicept at a dose of 160 mg significantly reduced disease activity (measured by ESSDAI) compared to placebo after 24 weeks, indicating its efficacy in treating this condition.

Telitacicept was well-tolerated with no serious adverse events reported, suggesting it is a safe treatment option for patients with primary Sjögren's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of telitacicept in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled, phase 2 trial. Xu, D., Fang, J., Zhang, S., et al.[2023]

In a phase III trial involving 52 patients with primary Sjögren's syndrome, rituximab treatment led to a statistically significant improvement in salivary gland ultrasound scores compared to placebo, indicating its efficacy in this condition.

Specifically, the rituximab group showed notable improvements in glandular definition, with odds ratios suggesting a strong likelihood of response at both 16 and 48 weeks, supporting the potential of B cell depletion therapies in managing primary Sjögren's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rituximab on a salivary gland ultrasound score in primary Sjögren's syndrome: results of the TRACTISS randomised double-blind multicentre substudy. Fisher, BA., Everett, CC., Rout, J., et al.[2021]

Oral pilocarpine (10 mg daily) significantly improved subjective eye symptoms in patients with primary Sjögren's syndrome, showing a greater than 55 mm improvement on a visual analogue scale compared to artificial tears and inferior puncta occlusion treatments.

While pilocarpine also led to objective improvements in eye condition as measured by the rose bengal test, it did not increase tear production according to the Schirmer's-I test, and common side effects included headache and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren's syndrome: a randomised 12 week controlled study. Tsifetaki, N., Kitsos, G., Paschides, CA., et al.[2019]

Sjögren's Disease (SjD) is a complex autoimmune disorder that significantly impacts patients' quality of life due to symptoms like dryness and fatigue, highlighting the need for effective therapies.

Recent phase II/III studies suggest that categorizing SjD patients into biologically similar subgroups could enhance the efficacy of treatments, indicating a promising direction for future therapeutic development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging treatment for Sjögren's disease: a review of recent phase II and III trials. Fox, RI., Fox, CM., McCoy, SS.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06531395

NCT06531395 | A Study to Evaluate the Efficacy and ... Primary objective of the study is to evaluate the effect of abiprubart on an established systemic disease activity measure for Sjögren's Disease.

2. investors.kiniksa.com investors.kiniksa.com/news-releases/news-release-details/kiniksa-pharmaceuticals-announces-development-indication

Kiniksa Pharmaceuticals Announces Development ... “These Phase 2 data demonstrate that abiprubart is a potentially efficacious and well-tolerated therapeutic approach for multiple autoimmune ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S152169422500052X

Novel therapies in Sjögren's disease: A systematic review ... This systematic review aims to provide a comprehensive overview of recent SjD therapeutic advances, assess trial inclusivity with respect to sex/gender and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7789801/

Anti-CD40 antibody KPL-404 inhibits T cell-mediated ... KPL-404 efficiently blocked CD40L-CD40-mediated activation of B cells from patients with SjS and SLE, without affecting their anti-IgM responses or affecting ...

5. acrabstracts.org acrabstracts.org/abstract/efficacy-safety-pharmacokinetics-of-anti-cd40-antibody-abiprubart-in-patients-with-rheumatoid-arthritis-a-phase-2-randomized-placebo-controlled-12-week-treatment-proof-of-concept-study/

Efficacy, Safety, Pharmacokinetics of Anti-CD40 Antibody ... Abiprubart was well-tolerated in pts with b/tsDMARD-refractory RA, and reductions in DAS28-CRP at Wk 12 for all abiprubart groups were greater than PBO.

6. kiniksa.com kiniksa.com/2021-acr-samant-kpl-404-ph1.pdf

2021-acr-samant-kpl-404-ph1.pdf KPL-404 was well tolerated with no safety signals based on the evaluation of AEs, clinical laboratory findings, and vital signs measurements in participants ...