Kiniksa Pharmaceuticals International has unveiled the comprehensive design for its upcoming Phase 2/3 clinical trial of KPL-387 in recurrent pericarditis, positioning the investigational monoclonal antibody as a potential monthly treatment option for patients with this challenging cardiovascular condition. The trial is expected to initiate in mid-2025, with Phase 2 data anticipated in the second half of 2026.
Novel IL-1 Receptor Targeting Approach
KPL-387 represents an independently developed, fully human immunoglobulin G2 (IgG2) monoclonal antibody that binds human interleukin-1 receptor 1 (IL-1R1), effectively inhibiting the signaling activity of the cytokines interleukin-1α (IL-1α) and interleukin-1β (IL-1β). This mechanism targets the inflammatory pathways central to pericarditis pathophysiology.
"We leveraged our expertise in this indication and experience with the RHAPSODY study design to plan this pivotal phase 2/3 study. We believe KPL-387 could provide a meaningful addition to the therapeutic options available to patients," said John F. Paolini, M.D., Ph.D., FACC, Chief Medical Officer of Kiniksa.
Comprehensive Three-Part Trial Design
The Phase 2/3 clinical trial will evaluate the efficacy and safety of KPL-387 administered subcutaneously in patients with recurrent pericarditis through three overlapping components combined into a single protocol: a dose-focusing portion (Phase 2), a pivotal portion (Phase 3), and long-term extensions.
Dose-Focusing Phase
The dose-focusing portion will enroll up to approximately 80 participants with recurrent pericarditis, randomized in a 1:1:1:1 ratio to receive four different dosing regimens: KPL-387 300 mg subcutaneously biweekly, 300 mg subcutaneously monthly, 100 mg subcutaneously biweekly, and 100 mg subcutaneously monthly. The primary efficacy endpoint is time to treatment response at Week 24, with active participants eligible to enter long-term extensions.
Pivotal Phase Design
Following the dose-focusing portion, up to approximately 85 patients with recurrent pericarditis will be enrolled in the pivotal portion. This phase features a two-period design: a single-blind run-in period where all participants receive KPL-387 while conventional oral pericarditis medications are weaned and discontinued, followed by an event-driven, double-blind, randomized withdrawal period for participants achieving clinical response.
During the randomized withdrawal period, participants will be randomized in a 1:1 ratio to receive either KPL-387 or placebo. The primary efficacy endpoint is time to first-adjudicated pericarditis recurrence during this withdrawal period.
Monthly Dosing Profile Advantage
Dr. Paolini emphasized the potential convenience advantage of KPL-387's dosing profile: "We are eager to advance KPL-387, with its target profile of monthly dosing in a single subcutaneous injection in a liquid formulation, through this pivotal Phase 2/3 clinical trial and to patients in need."
The Phase 1 first-in-human single ascending dose study data support this monthly dosing profile, providing the foundation for the current trial design. Kiniksa believes KPL-387 could expand treatment options for recurrent pericarditis patients by enabling dosing with a single monthly subcutaneous injection in a liquid formulation.
Clinical Development Timeline
The company expects to initiate the study in the middle of 2025, with data from the dose-focusing portion expected in the second half of 2026. This timeline positions KPL-387 as a potential near-term addition to the therapeutic landscape for recurrent pericarditis, a condition with significant unmet medical need.
The trial design reflects Kiniksa's focus on cardiovascular indications and builds upon the company's experience in developing novel therapies for diseases with unmet need. As a biopharmaceutical company dedicated to improving patient outcomes, Kiniksa's portfolio is based on strong biologic rationale and validated mechanisms with potential for differentiation.
