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A Phase 2 Study to Evaluate the Efficacy and Safety of Transitioning to KPL-387 Monotherapy in Participants with Well-Controlled Recurrent Pericarditis

Trial ID: 2025-523234-66-00
Protocol: KPL-387-C212
Sponsor: Kiniksa Pharmaceuticals GmbH

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Diseases & Conditions

Pericarditis

Objectives

The primary objective of this phase 2 study is to characterize the efficacy of various dosing regimens during the transition from standard therapies to KPL-387 monotherapy in participants with well-controlled recurrent pericarditis. Additionally, the long-term extension phase aims to evaluate the sustained efficacy of KPL-387. The study focuses on dose response, pharmacodynamics, safety, efficacy, pharmacokinetics, and pharmacogenomics.

Participants

This study involves 58 participants diagnosed with well-controlled recurrent pericarditis. The study population consists of both male and female patients aged between 18 and 80 years. Eligible participants must have a body weight of at least 40 kg and a documented history of the condition consistent with established clinical guidelines. Individuals must currently exhibit stable disease, characterized by a C-reactive protein level below 0.5 mg/dL and a pain score of 3 or less on the numerical rating scale. Participants must have undergone standard therapy for at least 3 months and be on a stable dosing regimen. To maintain data integrity, participants are required to refrain from significant changes to exercise patterns. The study objectives are:

To characterize the efficacy of dosing regimens used to transition from prior therapies to monotherapy.
To evaluate the long-term efficacy of the investigational product.

Plans and Procedures

This Phase 2 study is designed as a posology study with a long-term extension to evaluate the efficacy and safety of transitioning from standard therapies to KPL-387 monotherapy in participants with well-controlled recurrent pericarditis. The research methodology aims to characterize the efficacy of various dosing regimens used during the transition and to assess the long-term efficacy of the investigational product. The trial involves a screening visit to confirm eligibility, followed by the initiation of subcutaneous injection of KPL-387. The posology study phase evaluates the proportion of participants free from pericarditis recurrence by week 16, while the long-term extension phase assesses the annualized rate of recurrence through the end of the extension period. Study events are confirmed by a clinical endpoint committee. Total study duration is estimated to extend from early 2026 through April 2029.

Treatment

The investigational product is KPL-387, provided as a solution for injection. This substance is administered via subcutaneous injection to evaluate its efficacy and safety as a monotherapy in participants with recurrent pericarditis.

Participants transition to the experimental treatment from standard therapies used for the management of well-controlled disease. The study design includes a posology phase to characterize different dosing regimens and a long-term extension to evaluate sustained clinical effects.

Efficacy

The efficacy of the transition regimens from standard therapies to KPL-387 monotherapy will be assessed in participants with well-controlled recurrent pericarditis. The primary efficacy endpoint for the posology study is the proportion of participants free from pericarditis recurrence at week 16. Only recurrences confirmed by a Clinical Endpoint Committee will be utilized to establish this parameter.

In the long-term extension, efficacy will be evaluated through the annualized rate of pericarditis recurrence until the end of the extension period. For both study components, only recurrences confirmed by the Clinical Endpoint Committee will be considered as events for analysis.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Each participant must meet all of the following criteria to be enrolled in this study: Is capable of understanding the written ICF, has provided signed written informed consent, and agrees to comply with protocol requirements.
Is > 18 years of age and < 81 years of age at Screening.
Has a body weight of at least 40 kg at Screening.
Has a history of pericarditis that in the opinion of the Investigator was consistent with the 2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler 2015) based on the documented available data, fulfilling at least 2 of the following 4 criteria: • Pericarditic chest pain • Pericardial rub • New widespread ST segment elevation or PR segment depression according to ECG findings • Pericardial effusion (new or worsening). Note: Additional supporting findings include: Elevation of markers of inflammation (i.e. C-reactive protein, erythrocyte sedimentation rate, and white blood cell count); Evidence of pericardial inflammation by an imaging technique (CT, CMR).
Currently has RP which is well-controlled, i.e., including having CRP < 0.5 mg/dL within 14 days of Baseline and a pericarditis pain NRS score ≤ 3 at Baseline.
Has a documented history of CRP elevation (> 1 mg/dL) associated with at least one prior acute pericarditis episode, whether the incident event or any pericarditis recurrence.
Has received treatment for RP for at least 3 months prior to Baseline with standard therapy(ies) and is currently on a stable dosing regimen as listed in the protocol section 4.1, page 43
Participant is willing to and, in the opinion of the Investigator, is expected to be able to discontinue all permitted/prior pericarditis medications after initiation of study drug within protocol defined windows.
Routine adult vaccinations should be up to date or offered at least 2 weeks prior to first study drug administration according to regional and national guidelines based on medical history or presence of risk factors, in the opinion of the Investigator.
If female, must be either postmenopausal (defined as no menses for 12 months without other medical cause), permanently surgically sterile (i.e., removal of ovaries, fallopian tubes, and/or uterus), or, for women of childbearing potential, must: Be nonpregnant, nonlactating, and agree to remain abstinent or use a highly effective method of contraception with a failure rate of < 1% per year from the Screening Visit until after the end of study participation and at least 8 weeks after the last KPL-387 dose. Examples of contraception methods with a failure rate of < 1% per year include: a. Hormonal contraceptives associated with inhibition of ovulation (stable dose for at least 4 weeks prior to first dose of KPL-387); hormonal contraceptive methods must be supplemented by a barrier method b. Hormone-releasing or copper intrauterine device c. Bilateral tubal occlusion d. Vasectomized male partner e. Abstinence from heterosexual intercourse; the reliability of sexual abstinence should be evaluated based on duration of the study and usual lifestyle of the participant. Intermittent abstinence (such as calendar, ovulation, symptothermal or post-ovulation) and withdrawal are not considered acceptable contraceptive methods *The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
Sexually active male participants must have documented vasectomy or must agree to use a condom or method of contraception with a failure rate of <1% per year, as defined above with their partners of childbearing potential through the end of study participation and at least 8 weeks after last KPL-387 dose.
Male participants must agree to refrain from donating sperm through the end of study participation and at least 8 weeks after last study drug dose. Female participants must agree to refrain from donating eggs through the end of study participation and at least 8 weeks after last KPL-387 dose.
Agrees to refrain from lifestyle changes that may affect pericarditis symptoms (e.g., significant changes to exercise pattern) except as recommended by the Investigator from the time the ICF is signed through the end of the Posology Period.

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Exclusion Criteria

Participants meeting any of the following criteria will be excluded from this study: Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies, including: a. Tuberculosis (TB) b. Neoplastic, purulent, or radiation etiologies c. Post-thoracic blunt trauma (e.g., motor vehicle accident) d. Systemic autoimmune diseases e. Concurrent extensive myocardial inflammation and/or injury as evidenced by: • New regional wall motion abnormalities or new global left ventricular systolic dysfunction • [CCI]
Has had a pericarditis recurrence in the last 3 months prior to Baseline.
Has clinical worsening of pericarditis signs/symptoms (e.g., more than mild pericardial pain) or clinical suspicion of impending pericarditis recurrence during Screening.
Has had prior lack of efficacy while receiving anakinra (100 mg SC once-daily dosing regimen) or rilonacept (160 mg SC once-weekly dosing regimen), or discontinuation of therapy due to safety concerns (other than local injection site reactions [ISRs])
Is receiving/has received concurrent or prior treatments within the washout periods prior to first dose of study drug, defined in the table on page 43 section 4.2
Has a positive (or 2 indeterminate) QuantiFERON® or other interferon gamma release assay (IGRA) test results unless confirmation of prior completion of appropriate treatment for latent TB and no evidence of active TB. a. IGRA test will be performed during Screening unless participant has a previously documented negative IGRA result within 8 weeks prior to Screening or documented prior positive IGRA at any time. b. An indeterminate IGRA test should be repeated. c. A positive or two successive indeterminate IGRA results should be considered a positive diagnostic TB test. d. An indeterminate followed by a negative IGRA test should be considered a negative diagnostic TB test.
Has a history of immunodeficiency.
Has a positive human immunodeficiency virus (HIV) test result. HIV test will be performed during Screening unless participant has a previously documented negative HIV result within 8 weeks prior to Screening.
Has chest x-ray at Screening (or history of results within 12 weeks before receiving first study drug administration), with evidence of malignancy, abnormality consistent with prior or active TB infection, active infection, or any other medical condition that could adversely affect study participation or interfere with study evaluations, in the opinion of the Investigator.
Has positive or intermediate results for hepatitis C virus (HCV) infection or chronic active hepatitis B infection at Screening as defined below. a. Hepatitis C antibody positive unless confirmed to have negative polymerase chain reaction (PCR) test of HCV RNA b. Hepatitis B surface antigen positive c. Hepatitis B anti-core antibody positive and anti-surface antibody negative d. Consultation with a liver disease expert is recommended prior to enrollment of any participants with hepatitis B anti-core antibody positive and anti-surface antibody positive results.
Has an estimated glomerular filtration rate < 30 mL/min, by laboratory standard practice (e.g., MDRD formula).
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).
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.
Has had a serious infection, has been admitted to the hospital for an infection, or has been treated for a documented infection requiring more than one dose of parenteral (IV or intramuscular) antibiotics within 8 weeks prior to first study drug administration or has been treated with oral (or single dose parenteral antibiotics for a documented infection within 2 weeks prior to first study drug administration).
Has had an organ transplant (except corneal transplant performed more than 3 months prior to first study drug administration).
Has most recent Screening laboratory test results indicating any of the following criteria: a. Hemoglobin level <10.0 g/dL b. WBC count <3.0 × 103/μL c. Neutrophil count <1.5 × 103/μL d. Platelet count <100 × 103/μL e. Total bilirubin level >1.5 × the ULN unless the test results are consistent with those for Gilbert’s syndrome f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 × ULN
Has a known hypersensitivity to KPL-387 or to any of its excipients.
Has any medical condition that, in the opinion of the Investigator, could interfere with protocol compliance, evaluation of the study drug effects, or interpretation of participant safety events or confound the study results. This includes but is not limited to significant concomitant cardiac, renal, neurological, endocrinological, metabolic, pulmonary, or gastrointestinal disease, and psychiatric or substance use disorders.
Is not likely to be compliant with the study protocol, in the opinion of the Investigator.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
France	Recruiting	02 Jan 2026	3
Germany	Recruiting	02 Jan 2026	3
Greece	Recruiting	02 Jan 2026	3
Italy	Recruiting	02 Jan 2026	8
Poland	Recruiting	02 Jan 2026	2
Spain	Recruiting	02 Jan 2026	3

Sites & Investigators

Research sites

Hospital Vall d’Hebron Ecg Medica S.L.Clinique Saint Exupery Hippokration Hospital

Investigators

Leonidas P.Krzysztof O.George L.Alessandro A.

Investigational Products

Details about the medicinal products being studied in this clinical trial.

Product Name	Role in Trial	Formulation	Administration	Max Daily Dose	Treatment Duration	EU MP Number
KPL-387	Test	SOLUTION FOR INJECTION	SUBCUTANEOUS INJECTION	00	28	PRD12512392