A Pilot Study of KPL-914 in Recurrent Pericarditis

NCT ID: NCT03980522

Last Updated: 2021-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-24
• Study Completion Date: 2019-05-17

Brief Summary

The purpose of this study is to assess the preliminary efficacy and safety of KPL-914 treatment in participants with recurrent pericarditis.

Detailed Description

This is an open-label, single-arm pilot study to explore clinical and biochemical endpoints of pericarditis symptomatology and to collect data to assess inter- and intra-subject variability on both at-baseline and on-treatment parameters. This study consists of 5 distinct Parts, and all participants will be treated with once-weekly subcutaneously (SC)-administered injections of KPL-914.There is an optional 18-week extension period.

Conditions

Recurrent Pericarditis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

KPL-914: Part 1 Participants

Part 1 enrolls symptomatic participants with recurrent idiopathic pericarditis (RIP) with an elevated marker of systemic inflammation (C-reactive protein \[CRP\] \> 1mg/dL).

Group Type: EXPERIMENTAL

KPL-914

Intervention Type: DRUG

KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration.

Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks.

Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL.

Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.

KPL-914: Part 2 Participants

Part 2 enrolls symptomatic participants with RIP with CRP ≤1 mg/dL which, in the opinion of the Investigator, can be attributed to concomitant medications (e.g., corticosteroids) and with pericardial inflammation present on cardiac magnetic resonance imaging (MRI) confirmed by the imaging core lab.

Group Type: EXPERIMENTAL

KPL-914

Intervention Type: DRUG

KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration.

Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks.

Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL.

Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.

KPL-914: Part 3 Participants

Part 3 enrolls participants with corticosteroid-dependent RIP not experiencing symptoms which would meet the diagnostic criteria for a flare of pericarditis.

Group Type: EXPERIMENTAL

KPL-914

Intervention Type: DRUG

KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration.

Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks.

Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL.

Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.

KPL-914: Part 4 Participants

Part 4 enrolls symptomatic participants with recurrent post pericardiotomy syndrome (PPS) with an elevated marker of systemic inflammation (CRP \> 1mg/dL).

Group Type: EXPERIMENTAL

KPL-914

Intervention Type: DRUG

KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration.

Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks.

Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL.

Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.

KPL-914: Part 5 Participants

Part 5 enrolls participants with corticosteroid-dependent recurrent PPS not experiencing symptoms which would meet the diagnostic criteria for a flare of pericarditis.

Group Type: EXPERIMENTAL

KPL-914

Intervention Type: DRUG

KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration.

Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks.

Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL.

Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.

Interventions

KPL-914

KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration.

Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks.

Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL.

Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.

Intervention Type: DRUG

Other Intervention Names

rilonacept

Eligibility Criteria

Inclusion Criteria

• Has given consent (or assent, if applicable) and signed an Informed Consent Form (ICF) (or informed assent form, if applicable).
• Male or female, of any ethnic origin.
• 6 to 75 years of age, inclusive.
• If used, has received non-steroidal anti-inflammatory drugs (NSAIDs), and/or colchicine and/or corticosteroids (in any combination) at stable dose levels for at least 7 days prior to study drug dosing (although stable doses for a shorter period will be acceptable if in the opinion of the Investigator, in consultation with the Sponsor, a shorter period of stability is not anticipated to alter the baseline CRP values) and is anticipated to continue these concomitant medications at these dose levels for the duration of the active Treatment Period.
• If female of child-bearing potential, must be nonpregnant and nonlactating and must agree to use an effective method of contraception, e.g., hormonal contraception or double-barrier birth control.
• Is able to adequately maintain a medication diary.
• Agrees to refrain from making any new, major life-style changes that may affect pericarditis symptoms (e.g., starting a new diet or changing exercise pattern) from the time of signature of the ICF (or informed assent form, if applicable) to the End-of-Trial Visit.

Parts 1, 2 and 4:

Subjects eligible for Parts 1, 2 and 4 have to present during a symptomatic episode of recurrent idiopathic pericarditis (RIP; Parts 1 and 2) and post pericardiotomy syndrome (PPS; Part 4) and a history of at least one pericarditis recurrence. They can be enrolled into Part 1 or 4 if the CRP value at screening is >1 mg/dL, and into Part 2 if a CRP ≤1 mg/dL (attributed to concomitant medications e.g., corticosteroids), and there is an evidence of pericardial inflammation on cardiac MRI confirmed by the imaging core lab.

Enrollment into Part 3 and 5:

Subjects eligible for Part 3 of this study have to present with corticosteroid-dependent RIP or PPS and history of at least 2 pericarditis recurrences.

Exclusion Criteria

• Has a diagnosis of pericarditis that was secondary to specific excluded etiologies, including tuberculous, neoplastic, or purulent etiologies, post-myocardial infarction (early or late), thoracic trauma, myocarditis, or systemic diseases including autoinflammatory diseases, autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.).
• Has a history of immunodepression, including a positive human immunodeficiency virus test result.
• Has received treatment within the 6-month period before dosing with any systemic immunosuppressants (other than, for example, corticosteroids or mycophenolate) which, in the opinion of the Investigator (in consultation with the Sponsor), may interfere with the study endpoints.
• Currently receiving other interleukin (IL)-1 or IL-6 blockers, Janus-activating kinase (JAK) or tumor necrosis factor (TNF) inhibitors.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kiniksa Pharmaceuticals (UK), Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Operations Study Director

Role: STUDY_DIRECTOR

Kiniksa Pharmaceuticals (UK), Ltd.

Locations

Medstar Washington Hospital Center

Washington D.C., District of Columbia, United States

Avail Clinical Research, LLC

DeLand, Florida, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Affinity Clinical Research Institute

Oak Brook, Illinois, United States

Franciscan Physician Network Indiana Heart Physicians Cardiovascular Research Program

Indianapolis, Indiana, United States

Research Integrity, LLC

Owensboro, Kentucky, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Ellipsis Research Group

Brooklyn, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

BI Research Center

Houston, Texas, United States

University of Vermont Medical Center

Burlington, Vermont, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Swedish Medical Center

Seattle, Washington, United States

Countries

United States

References

Klein AL, Lin D, Cremer PC, Nasir S, Luis SA, Abbate A, Ertel A, LeWinter M, Beutler A, Fang F, Paolini JF. Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial. Heart. 2020 Nov 23;107(6):488-96. doi: 10.1136/heartjnl-2020-317928. Online ahead of print.

Reference Type: RESULT

PMID: 33229362 (View on PubMed)

Lin D, Klein A, Cella D, Beutler A, Fang F, Magestro M, Cremer P, LeWinter MM, Luis SA, Abbate A, Ertel A, Litcher-Kelly L, Klooster B, Paolini JF. Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept. BMC Cardiovasc Disord. 2021 Apr 21;21(1):201. doi: 10.1186/s12872-021-02008-3.

Reference Type: DERIVED

PMID: 33882846 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

KPL-914-C001

Identifier Type: -

Identifier Source: org_study_id