A Pilot Study of KPL-914 in Recurrent Pericarditis

NCT03980522 | Completed Phase 2 Results FDA Drug

• 1 other identifier: KPL-914-C001
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 14

Brief Summary

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

Conditions

Recurrent Pericarditis

Outcome Measures

Primary Outcomes (6)

• 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)

Study Arms (5)

KPL-914: Part 1 Participants

EXPERIMENTAL

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: Part 2 Participants

EXPERIMENTAL

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: Part 3 Participants

EXPERIMENTAL

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: Part 4 Participants

EXPERIMENTAL

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: Part 5 Participants

EXPERIMENTAL

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

Interventions

KPL-914 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.

Also known as: rilonacept

KPL-914: Part 1 Participants; KPL-914: Part 2 Participants; KPL-914: Part 3 Participants; KPL-914: Part 4 Participants; KPL-914: Part 5 Participants

Eligibility Criteria

• Age: 6 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kiniksa Pharmaceuticals (UK), Ltd.: lead

Study Sites (14)

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Affinity Clinical Research Institute

Oak Brook, Illinois, 60523, United States

Location

Franciscan Physician Network Indiana Heart Physicians Cardiovascular Research Program

Indianapolis, Indiana, 46237, United States

Location

Research Integrity, LLC

Owensboro, Kentucky, 42303, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Ellipsis Research Group

Brooklyn, New York, 11215, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

BI Research Center

Houston, Texas, 77084, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

Related Publications (2)

• 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.

  PMID: 33229362 RESULT

• 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.

  PMID: 33882846 DERIVED

MeSH Terms

Conditions

Pericarditis

Interventions

rilonacept

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Clinical Operations Study Director
• Organization: Kiniksa Pharmaceuticals (UK), Ltd. c/o Kiniksa Pharmaceuticals Corp.

studyinfo@kiniksa.com

1-781-431-9100

Study Officials

• Clinical Operations Study Director

  Kiniksa Pharmaceuticals (UK), Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2019
• First Posted: June 10, 2019
• Study Start: January 24, 2018
• Primary Completion: May 17, 2019
• Study Completion: May 17, 2019
• Last Updated: May 27, 2021
• Results First Posted: May 27, 2021

Record last verified: 2021-05

Locations

US (14)