A Pilot Study of KPL-914 in Recurrent Pericarditis

An Open-Label Pilot Study of KPL-914 in Recurrent Pericarditis

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

Study Overview

• Status: Completed
• Conditions: Recurrent Pericarditis
• Intervention / Treatment: Drug: KPL-914

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • Affinity Clinical Research Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Physician Network Indiana Heart Physicians Cardiovascular Research Program
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Research Integrity, LLC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • Brooklyn, New York, United States, 11215
      • Ellipsis Research Group
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Texas
    • Houston, Texas, United States, 77084
      • BI Research Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for All Participants:

• 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 for All Participants:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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).	Drug: 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.; Other Names: rilonacept
EXPERIMENTAL: 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.	Drug: 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.; Other Names: rilonacept
EXPERIMENTAL: 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.	Drug: 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.; Other Names: rilonacept
EXPERIMENTAL: 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).	Drug: 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.; Other Names: rilonacept
EXPERIMENTAL: 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.	Drug: 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.; Other Names: rilonacept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1, 2 and 4: Pretreatment C-Reactive Protein (CRP) Levels		Screening Visit 1 (Day -3 to Day 0), Screening Visit 2 (Day -3 to Day 0), Day 0, Baseline (defined as the last non-missing assessment prior to the first study drug administration)
Parts 1, 2 and 4: On-Treatment Change From Baseline Over Time in CRP Levels		Baseline, Treatment Period (TP) Weeks 2, 3, 4, 5, 6, TP Interval Evaluation (between Weeks 3-4), End of TP (up to Week 6), Extension Period (EP): Months 1, 2, 3, 4, EP Interval Evaluation (between Weeks 15-20), Final Visit (up to Week 25)
Parts 1, 2 and 4: Pretreatment Pain NRS Scores	The average level of pericarditis pain over previous 24 hours was assessed by participants at each visit using 11-point pain NRS (where "0" indicates "no pain" and "10" indicates pain "as bad as it could be").	Prescreening, Screening Visit 1 (Day -3 to Day 0), Screening Visit 2 (Day -3 to Day 0), Day 0, Baseline (defined as the last non-missing assessment prior to the first study drug administration)
Parts 1, 2 and 4: On-Treatment Change From Baseline Over Time in Pain NRS Scores	The average level of pericarditis pain over previous 24 hours was assessed by participants at each visit using 11-point pain NRS (where "0" indicates "no pain" and "10" indicates pain "as bad as it could be").	Baseline, Treatment Period (TP) Day 3, Weeks 2, 3, TP Interval Evaluation (between Weeks 3-4), 4, 5, 6, End of TP (up to Week 6), Extension Period (EP): Months 1, 2, 3, 4, EP Interval Evaluation (between Weeks 15-20), Final Visit (up to Week 25)
Parts 3 and 5: Change From Baseline Over Time in CRP Levels	Baseline is defined as the last non-missing assessment prior to the first study drug administration.	Baseline, TP Weeks 2, 3, Interval Evaluation Visit (Weeks 3-4), 4, 5, 6, End of TP Visit (Week 6), EP Months 1, 2, 3, 4, EP Interval Evaluation Visit (Week 15-Week 20), Final Visit (up to EP Month 4)
Parts 3 and 5: Change From Baseline Over Time in Pain NRS Scores	The average level of pericarditis pain over previous 24 hours was assessed by participants at each visit using 11-point pain NRS (where "0" indicates "no pain" and "10" indicates pain "as bad as it could be"). Baseline is defined as the last non-missing assessment prior to the first study drug administration.	Baseline, TP Day 3, TP Weeks 2, 3, Interval Evaluation Visit (Weeks 3-4), 4, 5, 6, End of TP Visit (Week 6), EP Months 1, 2, 3, 4, EP Interval Evaluation Visit (Week 15-Week 20), Final Visit (up to EP Month 4)

Collaborators and Investigators

• Sponsor: Kiniksa Pharmaceuticals (UK), Ltd.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 24, 2018
• Primary Completion (ACTUAL): May 17, 2019
• Study Completion (ACTUAL): May 17, 2019

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 6, 2019
• First Posted (ACTUAL): June 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 27, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Recurrence; Pericarditis; Anti-Inflammatory Agents; Rilonacept
• Other Study ID Numbers: KPL-914-C001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No