Clinical trial NCT07010159: Phase 2/3 Study of KPL-387 in Recurrent Pericarditis
Official title: A Phase 2/3 Efficacy and Safety Study of KPL-387 Treatment in Participants With Recurrent Pericarditis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Pericarditis
Pericarditis Acute
Recurrent Pericarditis
Keywords: Recurrence
Recurrent
Recurrent Pericarditis
KPL-387
Lead sponsor: Kiniksa Pharmaceuticals International, plc
Sponsor class: INDUSTRY
Collaborators: name: Kiniksa Pharmaceuticals, GmbH
First posted: 2025-06-08
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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.

Primary outcomes:
measure: Phase 2: Time to Treatment Response by Week 24
timeFrame: From Randomization up to Week 24
measure: Phase 3: Time to Pericarditis Recurrence
timeFrame: From first administration of study drug in the RW Period
measure: Long-Term Extension: Annualized rate of Pericarditis Recurrence
timeFrame: Up to 24 Months
Secondary outcomes:
measure: Phase 2: Time to CRP Normalization (CRP ≤ 0.5 mg/dL) by Week 24
timeFrame: From Randomization up to Week 24
measure: Phase 2: Time to Pain Response by Week 24
timeFrame: From Randomization up to Week 24
measure: 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
timeFrame: From Randomization up to Week 24
measure: Phase 2: Proportion of Participants With Normalization of CRP (CRP ≤ 0.5 mg/dL) Over Time by Week 24
timeFrame: From Randomization up to Week 24
measure: 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.
timeFrame: From Randomization up to Week 16
measure: Phase 2: Change from Baseline in SF-36v2® Physical Component Summary score through Week 24.
timeFrame: From Randomization up to Week 24
measure: Phase 2: Change from Baseline in SF-36v2® Mental Component Summary score through Week 24.
timeFrame: From Randomization to Week 24
measure: Phase 2: Proportion of participants with Protocol-Defined Pericarditis Recurrence by Week 24.
timeFrame: From Randomization to Week 24
measure: Phase 2: Change from Baseline in CRP through Week 24.
timeFrame: From Randomization up to Week 24
measure: Phase 2: Change from Baseline in pericarditis pain NRS score through Week 24.
timeFrame: From Randomization up to Week 24
measure: Phase 2: Change from RI Baseline in SF-36v2® Mental Component Summary score through the end of the RI Period
timeFrame: From Baseline up to the end of the RI Period
measure: Phase 3: Time to Treatment Response by the end of the RI Period
timeFrame: From Baseline up to end of the RI Period
measure: Phase 3: Time to Clinical Response by the end of the RI Period
timeFrame: From Baseline up to end of the RI Period
measure: Phase 3: Time to Pain Response by end of the RI Period
timeFrame: From Baseline up to end of the RI Period
measure: Phase 3: Time to CRP normalization by the end of the RI Period
timeFrame: From Baseline up to end of the RI Period
measure: Phase 3: Change from RI Baseline in SF-36v2® Physical Component Summary score through the end of the RI Period.
timeFrame: From Baseline up to end of the RI Period
measure: 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.
timeFrame: From Baseline up to end of the RI Period
measure: Phase 3: Change from RI Baseline in daily pericarditis pain NRS score through the end of the RI Period.
timeFrame: From Baseline up to end of the RI Period
measure: Phase 3: Change from RI Baseline in CRP through the end of the RI Period.
timeFrame: From Baseline up to end of the RI Period
measure: Phase 3: Proportion of participants who maintained Clinical Response at RW Week 16.
timeFrame: From Randomization up to RW Week 16
measure: Phase 3: Percentage of days with no or minimal pericarditis pain through RW Week 16.
timeFrame: From Randomization up to RW Week 16
measure: Phase 3: Change from RW Baseline in SF-36v2® Physical Component Summary score at RW Week 16.
timeFrame: From Randomization up to RW Week 16
measure: Phase 3: Change from RW Baseline in SF-36v2® Mental Component Summary score at RW Week 16
timeFrame: From Randomization up to RW Week 16
measure: Phase 3: Change from RW Baseline in pain NRS score during the RW Period.
timeFrame: From Randomization through the end of the RW Period
measure: Phase 3: Change from RW Baseline in CRP during the RW Period
timeFrame: From Randomization through the end of the RW Period
measure: Long-Term Extension: Proportion of participants who maintained Clinical Response through the end of the LTE.
timeFrame: Up to 24 months
measure: Long-Term Extension: Percentage of days with no or minimal pericarditis pain through the end of the LTE Period.
timeFrame: Up to 24 months
measure: Long-Term Extension: Change from LTE Baseline in SF-36v2® Physical Component Summary score through the end of the LTE Period.
timeFrame: Up to 24 months
measure: Long-Term Extension: Change from LTE Baseline in SF-36v2® Mental Component Summary score through the end of the LTE Period.
timeFrame: Up to 24 months
measure: Long-Term Extension: Change from LTE baseline in pain NRS score through the end of the LTE Period.
timeFrame: Up to 24 months
Other outcomes:
Locations:
Study officials:
References: