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

NCT ID: NCT03737110

Last Updated: 2023-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-07
• Study Completion Date: 2022-06-30

Brief Summary

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

Detailed Description

In the single-blind run-in (RI) period, rilonacept 320 mg (or 4.4 mg/kg in pediatric participants ≥12 and <18 years old) subcutaneous (SC), followed by 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and <18 years old) injections once weekly.

During the Randomized-Withdrawal (RW) period, eligible participants are randomized 1:1 to double-blinded administration of study drug:

• Rilonacept 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and <18 years old) SC injections once weekly
• Matching 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 numerical rating scale (NRS) and have 1 C-reactive protein (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 subjects]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection.

Upon completion of the RW period (i.e., when the prespecified number of primary efficacy endpoints [clinical events committee-confirmed pericarditis recurrence] events have occurred), all participants who did not discontinue study drug have an option to continue treatment with open-label rilonacept in the Long-Term Extension (LTE) or to withdraw from the study. Participants still in the RI period at the time that the RW period has ended and the LTE is opened will have the option to enter the LTE directly when they have completed the RI period and have met the definition of clinical response or to withdraw from the study.

Conditions

Recurrent Pericarditis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Rilonacept

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.

Group Type: EXPERIMENTAL

Rilonacept

Intervention Type: 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

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Rilonacept

Intervention Type: 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

Placebo

Intervention Type: DRUG

Placebo SC injections once weekly

Interventions

Rilonacept

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

Intervention Type: DRUG

Placebo

Placebo SC injections once weekly

Intervention Type: DRUG

Other Intervention Names

KPL-914; Arcalyst® for Cryopyrin-Associated Periodic Syndromes (CAPS)

Eligibility Criteria

Inclusion Criteria

1. Male or female aged 12 or older

2. Has a diagnosis of recurrent pericarditis

3. Must provide Informed Consent

4. Presents with at least the third episode of pericarditis during screening.

5. 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

6. 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.

7. Must be up-to-date with all immunizations, in agreement with current local immunization guidelines for immunosuppressed subjects, before first study drug administration.

8. Is able to adequately maintain a daily subject diary according to protocol.

9. 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.

Exclusion Criteria

1. Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies.

2. Has a history of immunosuppression, including positive human immunodeficiency virus (HIV) test results.

3. Has a history of myeloproliferative disorder.

4. Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis.

5. Has a history of active or latent tuberculosis (TB) prior to screening

6. 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.

7. Has a history of positive or intermediate results for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody at screening.

8. 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).

9. 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.

10. Has had an organ transplant.

11. In the Investigator's opinion, has a history of alcoholism or drug/chemical abuse within 2 years before screening.

12. Has a known hypersensitivity to rilonacept or to any of its excipients.

13. 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.

14. In the Investigator's opinion, has any other medical condition that could adversely affect the subject's participation or interfere with study evaluations.

• Minimum Eligible Age: 12 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

Cedars-Sinai Medical Institute

Los Angeles, California, United States

Arthritis and Rheumatology of Georgia

Atlanta, Georgia, United States

The Loretto Hospital

Chicago, Illinois, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Mayo Clinic - PPDS

Rochester, Minnesota, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Cardiology Consultants of Philadelphia

Yardley, Pennsylvania, United States

Intermountain Healthcare

Murray, Utah, 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

HeartCare Partners Clinical Research Unit

Milton, Queensland, Australia

GenesisCare - Cardiology Research

Doncaster East, Victoria, Australia

Bnai Zion Medical Center

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Galilee Medical Center

Nahariya, , Israel

Sheba Medical Center at Tel-Hashomer

Ramat Gan, , Israel

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, Italy

ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico

Milan, Lombardy, Italy

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Countries

United States; Australia; Israel; Italy

References

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.

Reference Type: BACKGROUND

PMID: 33200890 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39044797 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39022168 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38471825 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37163222 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36316102 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36250662 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32866928 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002719-87

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KPL-914-C002

Identifier Type: -

Identifier Source: org_study_id