Study to Assess the Efficacy and Safety of Rilonacept Treatment in Participants With Recurrent Pericarditis

NCT03737110 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: KPL-914-C0022018-002719-87
• Study Type: interventional
• Target: 86
• Locations: 4 countries
• Sites: 21

Brief Summary

The primary objective of this study was to assess the efficacy of rilonacept treatment in participants with recurrent pericarditis.

Conditions

Recurrent Pericarditis

Outcome Measures

Primary Outcomes (1)

• Time to Pericarditis Recurrence in the RW Period

  Time to pericarditis recurrence (from randomization to 1st recurrence). Kaplan-Meier. Clinical Events Committee (CEC)-confirmed recurrences used for primary analysis. Recurrence defined as recurrence typical pericarditis pain with supportive objective evidence. CEC-adjudicated recurrences defined as:1) Re-appearance/worsening pericarditis pain (1 NRS ≥ 4) AND elevated CRP (≥1.0 mg/dL) on same day/separated by ≤ 7 days OR 2) Re-appearance/worsening pericarditis pain (1 NRS ≥ 4) AND abnormal CRP (\> 0.5 mg/dL) on same day/separated by ≤ 7 days AND 1 supportive evidence OR 3) Re-appearance/worsening pericarditis pain (no NRS ≥ 4) AND elevated CRP (≥ 1.0 mg/dL) not attributable to other causes AND 1 supportive evidence. Supportive evidence: White blood cell count \> upper limit normal, fever \> 38C, pericardial rub, electrocardiogram changes consistent with pericarditis, new/worsening pericardial effusion (echocardiogram), new/worsening pericardial inflammation (magnetic resonance imaging).

  RW Period (mean 24.8 weeks)

Secondary Outcomes (63)

• Major Secondary Efficacy Endpoint: Percentage of Participants Who Maintained Clinical Response at Week 16 of the RW Period

  RW Period Week 16

• Major Secondary Efficacy Endpoint: Percentage of Days With No or Minimal Pericarditis Pain at Week 16 of the RW Period

  RW Period Week 16

• Major Secondary Efficacy Endpoint: Percentage of Participants With Absent or Minimal Pericarditis Symptoms Based on the Patient Global Impression of Pericarditis Severity (PGIPS) at Week 16 of the RW Period

  RW Period Week 16

• Percentage of Participants Who Maintained Clinical Response at Week 24 of the RW Period

  RW Period Week 24

• Percentage of Participants Who Maintained Clinical Response at Week 8 of the RW Period

  RW Period Week 8

Study Arms (2)

Rilonacept

EXPERIMENTAL

RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly. RW period: eligible participants randomized to double-blinded administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL \[either on the same day or separated by no more than 7 days\]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept \[or 4.4 mg/kg for pediatric participants\]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection. LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly.

Drug: Rilonacept

Placebo

PLACEBO COMPARATOR

RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly. RW period: eligible participants randomized to placebo SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL \[either on the same day or separated by no more than 7 days\]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept \[or 4.4 mg/kg for pediatric participants\]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection. LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly.

Drug: Rilonacept; Drug: Placebo

Interventions

Rilonacept DRUG

Rilonacept 320 mg (or 4.4 mg/kg in pediatric participants ≥12 and \<18 years old) SC , followed by 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and \<18 years old) injections once weekly

Also known as: KPL-914, Arcalyst® for Cryopyrin-Associated Periodic Syndromes (CAPS)

Placebo; Rilonacept

Placebo DRUG

Placebo SC injections once weekly

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 12 or older
• Has a diagnosis of recurrent pericarditis
• Must provide Informed Consent
• Presents with at least the third episode of pericarditis during screening.
• Has received nonsteroidal anti-inflammatory drugs (NSAIDs) and/or colchicine and/or corticosteroids (in any combination), if used, at stable dose levels (or at least not increased) for at least 3 days prior to first study drug administration
• Female subjects must be postmenopausal, or incapable of pregnancy or permanently sterile, or if of childbearing potential must agree to use highly-effective method of contraception.
• Must be up-to-date with all immunizations, in agreement with current local immunization guidelines for immunosuppressed subjects, before first study drug administration.
• Is able to adequately maintain a daily subject diary according to protocol.
• Agrees to refrain from making any new, major lifestyle changes that may affect pericarditis symptoms (e.g., changing exercise pattern) from the time that the informed consent form (ICF) is signed through the end of the double-blind randomized withdrawal period.

You may not qualify if:

• Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies.
• Has a history of immunosuppression, including positive human immunodeficiency virus (HIV) test results.
• Has a history of myeloproliferative disorder.
• Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis.
• Has a history of active or latent tuberculosis (TB) prior to screening
• Has chest x-ray at screening or within 12 weeks before receiving first administration of study drug, with evidence of malignancy or abnormality consistent with prior or active TB infection.
• Has a history of positive or intermediate results for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody at screening.
• 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, including, but not limited to, chronic renal infection, chronic chest infection, sinusitis, recurrent urinary tract infection, or an open, draining infected skin wound.
• Has had an organ transplant.
• In the Investigator's opinion, has a history of alcoholism or drug/chemical abuse within 2 years before screening.
• Has a known hypersensitivity to rilonacept or to any of its excipients.
• Has received an investigational drug during the 30 days before screening or is planning to receive an investigational drug (other than that administered during this study) or use an investigational device at any time during the study.
• In the Investigator's opinion, has any other medical condition that could adversely affect the subject's participation or interfere with study evaluations.

Sponsors & Collaborators

• Kiniksa Pharmaceuticals (UK), Ltd.: lead

Study Sites (21)

Cedars-Sinai Medical Institute

Los Angeles, California, 90048, United States

Location

Arthritis and Rheumatology of Georgia

Atlanta, Georgia, 30342, United States

Location

The Loretto Hospital

Chicago, Illinois, 60644, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55902, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Cardiology Consultants of Philadelphia

Yardley, Pennsylvania, 19067, United States

Location

Intermountain Healthcare

Murray, Utah, 84107, 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

HeartCare Partners Clinical Research Unit

Milton, Queensland, 40664, Australia

Location

GenesisCare - Cardiology Research

Doncaster East, Victoria, 3109, Australia

Location

Bnai Zion Medical Center

Haifa, Israel

Location

Shaare Zedek Medical Center

Jerusalem, Israel

Location

Galilee Medical Center

Nahariya, Israel

Location

Sheba Medical Center at Tel-Hashomer

Ramat Gan, Israel

Location

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, Italy

Location

ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico

Milan, Lombardy, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Location

Related Publications (8)

• Klein AL, Imazio M, Cremer P, Brucato A, Abbate A, Fang F, Insalaco A, LeWinter M, Lewis BS, Lin D, Luis SA, Nicholls SJ, Pano A, Wheeler A, Paolini JF; RHAPSODY Investigators. Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis. N Engl J Med. 2021 Jan 7;384(1):31-41. doi: 10.1056/NEJMoa2027892. Epub 2020 Nov 16.

  PMID: 33200890 BACKGROUND

• Cremer PC, Lin D, Luis SA, Petersen J, Abbate A, Jellis CL, Kwon D, Brucato A, Fang F, Insalaco A, LeWinter M, Lewis BS, Zou L, Nicholls SJ, Klein AL, Imazio M, Paolini JF; RHAPSODY Investigators. Pericardial late gadolinium enhancement and time to recurrence: a substudy from RHAPSODY, a phase 3 clinical trial of rilonacept in recurrent pericarditis. Eur Heart J Imaging Methods Pract. 2023 May 26;1(1):qyad003. doi: 10.1093/ehjimp/qyad003. eCollection 2023 May.

  PMID: 39044797 DERIVED

• Brucato A, Trotta L, Arad M, Cremer PC, Insalaco A, Klutstein M, LeWinter M, Lin D, Luis SA, Wasserstrum Y, Clair J, Wang S, Klein AL, Imazio M, Paolini JF; RHAPSODY Investigators. Absence of Pericarditis Recurrence in Rilonacept-Treated Patients With COVID-19 and SARS-CoV-2 Vaccination: Results From the RHAPSODY Long-term Extension. CJC Open. 2024 Mar 4;6(6):805-810. doi: 10.1016/j.cjco.2024.02.002. eCollection 2024 Jun.

  PMID: 39022168 DERIVED

• Imazio M, Klein AL, Brucato A, Abbate A, Arad M, Cremer PC, Insalaco A, LeWinter MM, Lewis BS, Lin D, Luis SA, Nicholls SJ, Sutej P, Wasserstrum Y, Clair J, Agarwal I, Wang S, Paolini JF; RHAPSODY Investigators. Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept. J Am Heart Assoc. 2024 Mar 19;13(6):e032516. doi: 10.1161/JAHA.123.032516. Epub 2024 Mar 12.

  PMID: 38471825 DERIVED

• Thomas GK, Bonaventura A, Vecchie A, van Tassell B, Imazio M, Klein A, Luis SA, Abbate A. Interleukin-1 Blockers for the Treatment of Recurrent Pericarditis: Pathophysiology, Patient-Reported Outcomes, and Perspectives. J Cardiovasc Pharmacol. 2024 Jun 1;83(6):503-510. doi: 10.1097/FJC.0000000000001435.

  PMID: 37163222 DERIVED

• Brucato A, Wheeler A, Luis SA, Abbate A, Cremer PC, Zou L, Insalaco A, Lewinter M, Lewis BS, Lin D, Nicholls S, Pancrazi M, Klein AL, Imazio M, Paolini JF. Transition to rilonacept monotherapy from oral therapies in patients with recurrent pericarditis. Heart. 2023 Jan 27;109(4):297-304. doi: 10.1136/heartjnl-2022-321328.

  PMID: 36316102 DERIVED

• Brucato A, Lim-Watson MZ, Klein A, Imazio M, Cella D, Cremer P, LeWinter MM, Luis SA, Lin D, Lotan D, Pancrazi M, Trotta L, Klooster B, Litcher-Kelly L, Zou L, Magestro M, Wheeler A, Paolini JF; RHAPSODY Investigators. Interleukin-1 Trap Rilonacept Improved Health-Related Quality of Life and Sleep in Patients With Recurrent Pericarditis: Results From the Phase 3 Clinical Trial RHAPSODY. J Am Heart Assoc. 2022 Oct 18;11(20):e023252. doi: 10.1161/JAHA.121.023252. Epub 2022 Oct 17.

  PMID: 36250662 DERIVED

• Klein AL, Imazio M, Brucato A, Cremer P, LeWinter M, Abbate A, Lin D, Martini A, Beutler A, Chang S, Fang F, Gervais A, Perrin R, Paolini JF. RHAPSODY: Rationale for and design of a pivotal Phase 3 trial to assess efficacy and safety of rilonacept, an interleukin-1alpha and interleukin-1beta trap, in patients with recurrent pericarditis. Am Heart J. 2020 Oct;228:81-90. doi: 10.1016/j.ahj.2020.07.004. Epub 2020 Jul 14.

  PMID: 32866928 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 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: November 9, 2018
• Study Start: January 7, 2019
• Primary Completion: May 29, 2020
• Study Completion: June 30, 2022
• Last Updated: September 6, 2023
• Results First Posted: July 13, 2021

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

IL (4); US (12); IT (3); AU (2)