Phase 2/3 Study of KPL-387 in Recurrent Pericarditis

Phase 2

Recruiting

• Conditions: Pericarditis; Pericarditis Acute; Recurrent Pericarditis
• Interventions: Drug: KPL-387; Drug: Placebo

• Registration Number: NCT07010159
• Lead Sponsor: Kiniksa Pharmaceuticals International, plc

Brief Summary

This study is being done to demonstrate whether KPL-387 is an effective and safe treatment for recurrent pericarditis.

Detailed Description

This clinical trial is comprised of 3 separate study parts: Phase 2, Phase 3, and Long-Term Extension. The primary objective of Phase 2 is to evaluate how well different dose regimens of KPL-387 control the pain and inflammation of pericarditis in a group of participants experiencing an acute episode of recurrent pericarditis. This part of the study will confirm the KPL-387 dose regimen to be further tested in Phase 3 and the Long-Term Extension. The primary objective of Phase 3 is to confirm the efficacy of KPL-387 for the treatment of recurrent pericarditis and reduction in risk of recurrence in an additional group of participants experiencing an acute episode of recurrent pericarditis. Participants who complete Phase 2 or Phase 3 may be eligible to participate in the Long-Term Extension. The primary objective of the Long-Term Extension is to assess the long-term efficacy of KPL-387 while maintaining long-term disease control. All of the study parts also have other objectives to learn about the safety, tolerability, concentration of KPL-387 in blood, and effects of KPL-387 on blood test markers of immune activity in recurrent pericarditis.

Study Timeline

• Study First Submitted: 2025-05-29
• Study First Submitted QC: 2025-05-29
• Study First Posted: 2025-06-08
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-01
• Last Update Posted: 2025-07-04
• Study Start: 2025-07-31
• Primary Completion: 2027-12-31
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 165

Inclusion Criteria

• Phase 2 and 3: Has a diagnosis of recurrent pericarditis
• Phase 2 and 3: Has signs and symptoms of recurrent pericarditis despite treatment with standard therapies
• Phase 2 and 3: Weighs at least 40 kg
• Phase 2: Taking NSAIDS and/or colchicine (in any combination)
• Phase 3: Taking NSAIDs and/or colchicine and/or glucocorticoids (in any combination)

Key

Exclusion Criteria

• Phase 2 and 3: Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies.
• Phase 2 and 3: Has received an investigational drug during the 4 weeks before screening or is planning to receive an investigational drug at any time during the study.
• Phase 2 and 3: Has a history of active or untreated, latent tuberculosis (TB) prior to screening.
• Phase 2 and 3: Has a history of immunodeficiency.
• Phase 2 and 3: Has a history of immunosuppression, including positive human immunodeficiency virus (HIV) test results.
• Phase 2 and 3: Has chest x-ray at Screening or within 12 weeks before first study drug administration, with evidence of malignancy, abnormality consistent with prior or active TB infection or active infection.
• Phase 2 and 3: Has a history of malignancy of any organ system within the past 5 years before Screening (other than a successfully treated non metastatic cutaneous squamous cell carcinoma or basal cell carcinoma and/or localized carcinoma in situ of the cervix).
• Phase 2 and 3: Has a known or suspected current active infection or a history of chronic or recurrent infectious disease (> 3 episodes in prior 12 months), including but not limited to, genitourinary infection, chest infection, sinusitis, or skin/soft tissue infection.
• Phase 2 and 3: Has had a serious infection, has been admitted to the hospital for an infection, or has been treated for a documented infection requiring antibiotics for a documented infection within 2 weeks prior to first study drug administration.
• Phase 2 and 3: Has had an organ transplant (except corneal transplant performed more than 3 months prior to first study drug administration).
• Phase 2 and 3: In the Investigator's opinion, has any other medical condition that could adversely affect the subject's participation or interfere with study evaluations.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 KPL-387 100mg SC q2wk	KPL-387	In Phase 2 Treatment Period KPL-387 will be administered by subcutaneous (SC) injection every 2 weeks (q2wk) through Week 22.
Phase 2 KPL-387 100mg SC q4wk	KPL-387	In Phase 2 Treatment Period, KPL-387 or placebo (alternating every 2 weeks) will be administered by SC injection q2wk through Week 22 to provide active drug administration every 4 weeks (q4wk) while maintaining treatment concealment.
Phase 2 KPL-387 100mg SC q4wk	Placebo	In Phase 2 Treatment Period, KPL-387 or placebo (alternating every 2 weeks) will be administered by SC injection q2wk through Week 22 to provide active drug administration every 4 weeks (q4wk) while maintaining treatment concealment.
Phase 2 KPL-387 300mg SC q2wk	KPL-387	In Phase 2 Treatment Period KPL-387 will be administered by SC injection q2wk through Week 22.
Phase 2 KPL-387 300mg SC q4wk	KPL-387	In Phase 2 Treatment Period, KPL-387 or placebo (alternating every 2 weeks) will be administered by SC injection q2wk through Week 22 to provide active drug administration q4wk while maintaining treatment concealment.
Phase 2 KPL-387 300mg SC q4wk	Placebo	In Phase 2 Treatment Period, KPL-387 or placebo (alternating every 2 weeks) will be administered by SC injection q2wk through Week 22 to provide active drug administration q4wk while maintaining treatment concealment.
Phase 3 KPL-387 SC	KPL-387	Run-In (RI) Period: participants receive single-blind KPL-387 Randomized Withdrawal (RW) Period: eligible participants are randomized (1:1 KPL-387 or placebo) to receive double-blinded KPL-387.
Phase 3 Placebo SC	Placebo	RW Period: eligible participants are randomized (1:1 KPL-387 or placebo) to receive double-blinded placebo.
Long-Term Extension	KPL-387	Participants from Phase 2 and Phase 3 who continue into the Long-Term Extension will receive KPL-387.

Primary Outcome Measures

Name	Time	Method
Long-Term Extension: Annualized rate of Pericarditis Recurrence	Up to 24 Months
Phase 2: Time to Treatment Response by Week 24	From Randomization up to Week 24
Phase 3: Time to Pericarditis Recurrence	From first administration of study drug in the RW Period

Secondary Outcome Measures

Name	Time	Method
Phase 3: Change from RI Baseline in SF-36v2® Physical Component Summary score through the end of the RI Period.	From Baseline up to end of the RI Period
Phase 3: Proportion of participants who maintained Clinical Response at RW Week 16.	From Randomization up to RW Week 16
Phase 2: Time to CRP Normalization (CRP ≤ 0.5 mg/dL) by Week 24	From Randomization up to Week 24
Phase 2: Time to Pain Response by Week 24	From Randomization up to Week 24
Phase 2: Percentage of Days With No or Minimal Pain (Numerical Rating Scale (NRS) ≤ 2) While on KPL-387 Treatment Over Time by Week 24	From Randomization up to Week 24
Phase 2: Proportion of Participants With Normalization of CRP (CRP ≤ 0.5 mg/dL) Over Time by Week 24	From Randomization up to Week 24
Phase 2: Time to resolution of pericarditis manifestations (i.e. echocardiogram [ECHO] abnormalities, electrocardiogram [ECG] abnormalities, and pericardial rub), when present at Baseline, by Week 16.	From Randomization up to Week 16
Phase 2: Change from Baseline in SF-36v2® Physical Component Summary score through Week 24.	From Randomization up to Week 24
Phase 2: Change from Baseline in SF-36v2® Mental Component Summary score through Week 24.	From Randomization to Week 24
Phase 2: Proportion of participants with Protocol-Defined Pericarditis Recurrence by Week 24.	From Randomization to Week 24
Phase 3: Time to Clinical Response by the end of the RI Period	From Baseline up to end of the RI Period
Phase 3: Time to Pain Response by end of the RI Period	From Baseline up to end of the RI Period
Phase 3: Time to CRP normalization by the end of the RI Period	From Baseline up to end of the RI Period
Phase 3: Time to resolution of pericarditis manifestations (i.e., ECHO abnormalities, ECG abnormalities, and pericardial rub), when present at RI Baseline, by the end of the RI period.	From Baseline up to end of the RI Period
Phase 3: Change from RI Baseline in daily pericarditis pain NRS score through the end of the RI Period.	From Baseline up to end of the RI Period
Phase 3: Change from RI Baseline in CRP through the end of the RI Period.	From Baseline up to end of the RI Period
Phase 3: Percentage of days with no or minimal pericarditis pain through RW Week 16.	From Randomization up to RW Week 16
Phase 3: Change from RW Baseline in SF-36v2® Physical Component Summary score at RW Week 16.	From Randomization up to RW Week 16
Phase 3: Change from RW Baseline in SF-36v2® Mental Component Summary score at RW Week 16	From Randomization up to RW Week 16
Phase 3: Change from RW Baseline in pain NRS score during the RW Period.	From Randomization through the end of the RW Period
Phase 3: Change from RW Baseline in CRP during the RW Period	From Randomization through the end of the RW Period
Long-Term Extension: Proportion of participants who maintained Clinical Response through the end of the LTE.	Up to 24 months
Long-Term Extension: Percentage of days with no or minimal pericarditis pain through the end of the LTE Period.	Up to 24 months
Long-Term Extension: Change from LTE Baseline in SF-36v2® Physical Component Summary score through the end of the LTE Period.	Up to 24 months
Long-Term Extension: Change from LTE Baseline in SF-36v2® Mental Component Summary score through the end of the LTE Period.	Up to 24 months
Long-Term Extension: Change from LTE baseline in pain NRS score through the end of the LTE Period.	Up to 24 months
Phase 2: Change from Baseline in CRP through Week 24.	From Randomization up to Week 24
Phase 2: Change from Baseline in pericarditis pain NRS score through Week 24.	From Randomization up to Week 24
Phase 2: Change from RI Baseline in SF-36v2® Mental Component Summary score through the end of the RI Period	From Baseline up to the end of the RI Period
Phase 3: Time to Treatment Response by the end of the RI Period	From Baseline up to end of the RI Period

Trial Locations

Locations (1)

Investigational Site 001; 🇺🇸 Columbus, Georgia, United States