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

Overview

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.

Interventions

• Drug KPL-387
  administered by subcutaneous injection
• Drug Placebo
  administered by subcutaneous injection

Primary outcome measures

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

Secondary outcome measures (12)

• Phase 2: Time to CRP Normalization (CRP ≤ 0.5 mg/dL) by Week 24 [Time frame: From Randomization up to Week 24]
• Phase 2: Time to Pain Response by Week 24 [Time frame: 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 [Time frame: 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 [Time frame: 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. [Time frame: From Randomization up to Week 16]
• Phase 2: Change from Baseline in SF-36v2® Physical Component Summary score through Week 24. [Time frame: From Randomization up to Week 24]
• Phase 2: Change from Baseline in SF-36v2® Mental Component Summary score through Week 24. [Time frame: From Randomization to Week 24]
• Phase 2: Proportion of participants with Protocol-Defined Pericarditis Recurrence by Week 24. [Time frame: From Randomization to Week 24]
• Phase 2: Change from Baseline in CRP through Week 24. [Time frame: From Randomization up to Week 24]
• Phase 2: Change from Baseline in pericarditis pain NRS score through Week 24. [Time frame: 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 [Time frame: From Baseline up to the end of the RI Period]
• Phase 3: Time to Treatment Response by the end of the RI Period [Time frame: From Baseline up to end of the RI Period]

Eligibility criteria

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)

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 27 centers

• Investigational Site 018 — Gilbert
• Investigational Site 053 — Phoenix
• Investigational Site 030 — Los Angeles
• Investigational Site 008 — San Francisco
• Investigational Site 044 — Santa Monica
• Investigational Site 058 — Ventura
• Investigational Site 016 — Westminster
• Investigational Site 001 — Columbus
• … and 19 more centers

Italy · 7 centers

• Investigational Site 029 — Genoa
• Investigational Site 040 — Genoa
• Investigational Site 056 — Milan
• Investigational Site 007 — Milan
• Investigational Site 050 — Padua
• Investigational Site 033 — Udine
• Investigational Site 041 — Varese

France · 6 centers

• Investigational Site 028 — Montpellier
• Investigational Site 021 — Paris
• Investigational Site 036 — Pessac
• Investigational Site 019 — Poitiers
• Investigational Site 037 — Toulouse
• Investigational Site 038 — Toulouse

Spain · 5 centers

• Investigational Site 048 — Barcelona
• Investigational Site 010 — Barcelona
• Investigational Site 024 — Madrid
• Investigational Site 011 — Murcia
• Investigational Site 057 — Valencia

United Kingdom · 4 centers

• Investigational Site 020 — London
• Investigational Site 047 — London
• Investigational Site 035 — London
• Investigational Site 017 — Southampton

Greece · 3 centers

• Investigational Site 034 — Athens
• Investigational Site 039 — Nea Ionia
• Investigational Site 032 — Voula

Poland · 2 centers

• Investigational Site 051 — Warsaw
• Investigational Site 031 — Warsaw

Serbia · 2 centers

• Investigational Site 025 — Belgrade
• Investigational Site 026 — Belgrade

Canada · 1 center

• Investigational Site 027 — Ottawa

Germany · 1 center

• Investigational Site 052 — Dresden

Identifiers

NCT: NCT07010159 · KPL-387-C211 · 2025-521933-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗