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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03737110

Registration number

NCT03737110

Ethics application status

Date submitted

30/10/2018

Date registered

9/11/2018

Date last updated

6/09/2023

Titles & IDs

Public title

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

Scientific title

Phase 3, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study With Open-label Extension, to Assess the Efficacy and Safety of Rilonacept Treatment in Subjects With Recurrent Pericarditis

Secondary ID [1]

2018-002719-87

Secondary ID [2]

KPL-914-C002

Universal Trial Number (UTN)

Trial acronym

RHAPSODY

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Recurrent Pericarditis

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Other

Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Rilonacept
Treatment: Drugs - Placebo

Experimental: 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.

Placebo comparator: 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.

Treatment: Drugs: 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

Treatment: Drugs: Placebo
Placebo SC injections once weekly

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Time to Pericarditis Recurrence in the RW Period

Timepoint [1]

RW Period (mean 24.8 weeks)

Secondary outcome [1]

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

Timepoint [1]

RW Period Week 16

Secondary outcome [2]

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

Timepoint [2]

RW Period Week 16

Secondary outcome [3]

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

Timepoint [3]

RW Period Week 16

Secondary outcome [4]

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

Timepoint [4]

RW Period Week 24

Secondary outcome [5]

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

Timepoint [5]

RW Period Week 8

Secondary outcome [6]

Percentage of Days With No or Minimal Pericarditis Pain at Week 24 of the RW Period

Timepoint [6]

RW Period Week 24

Secondary outcome [7]

Percentage of Days With No or Minimal Pericarditis Pain at Week 8 of the RW Period

Timepoint [7]

RW Period Week 8

Secondary outcome [8]

Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 24 of the RW Period Based on the PGIPS

Timepoint [8]

RW Period Week 24

Secondary outcome [9]

Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 8 of the RW Period Based on the PGIPS

Timepoint [9]

RW Period Week 8

Secondary outcome [10]

Percentage of Participants Without Pericarditis Recurrence in the First 24 Weeks of the RW Period

Timepoint [10]

up to 24 weeks in the RW Period

Secondary outcome [11]

Time to Pericarditis Pain = 4 on the NRS in the RW Period

Timepoint [11]

RW Period (mean 24.8 weeks)

Secondary outcome [12]

Time to CRP Level = 1 mg/dL in the RW Period

Timepoint [12]

RW Period (mean 24.8 weeks)

Secondary outcome [13]

Time to Pericardial Rub in the RW Period

Timepoint [13]

RW Period (mean 24.8 weeks)

Secondary outcome [14]

Time to Widespread ST-segment Elevation or PR-segment Depression on Electrocardiogram (ECG) in the RW Period

Timepoint [14]

RW Period (mean 24.8 weeks)

Secondary outcome [15]

Time to New or Worsening Pericardial Effusion on Echocardiography (ECHO) in the RW Period

Timepoint [15]

RW Period (mean 24.8 weeks)

Secondary outcome [16]

Number of Participants in ECHO Pericardial Effusion Size Categories at RW Period Baseline, RW Week 24 and Worst Post-baseline in the RW Period

Timepoint [16]

RW Period Baseline, RW Period Week 24, RW Period (mean 24.8 weeks)

Secondary outcome [17]

Change From RW Period Baseline Over Time in CRP Levels in RW Period

Timepoint [17]

RW Period Baseline, RW Period Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 56

Secondary outcome [18]

Change From RW Period Baseline Over Time in Weekly Average of Pericarditis Pain in the RW Period

Timepoint [18]

RW Period Baseline, RW Period Weeks 1-50, 54

Secondary outcome [19]

Percentage of Participants With Absent or Minimal Pericarditis Symptoms Over Time After RW Period Week 24 Based on the PGIPS

Timepoint [19]

RW Period Weeks 32, 40, 48, 56

Secondary outcome [20]

Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the RW Period Based on the Physician Global Assessment of Pericarditis Activity (PGA-PA)

Timepoint [20]

RW Period Baseline, RW Period Weeks 8, 16, 24, 32, 40, 48, 56

Secondary outcome [21]

Change From RW Period Baseline in Short Form-36 (SF-36) Physical and Mental Component Scores at RW Period Week 24

Timepoint [21]

RW Period Baseline, RW Period Week 24

Secondary outcome [22]

Change From RW Baseline in SF-36 Individual Scores at RW Period Week 24

Timepoint [22]

RW Period Baseline, RW Period Week 24

Secondary outcome [23]

Change From RW Period Baseline in the Short Form Health Survey-6 Domains (SF-6D) Utility Index Score at RW Period Week 24

Timepoint [23]

RW Period Baseline, RW Period Week 24

Secondary outcome [24]

Change From RW Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value to RW Period Week 24

Timepoint [24]

RW Period Baseline, RW Period Week 24

Secondary outcome [25]

Change From RW Period Baseline in Insomnia Severity Index (ISI) Total Score at RW Period Week 24

Timepoint [25]

RW Period Baseline, RW Period Week 24

Secondary outcome [26]

Change in ISI Categories From RW Period Baseline to RW Period Week 24

Timepoint [26]

RW Period Baseline (BL), RW Period Week (Wk) 24

Secondary outcome [27]

Percentage of Participants Using Oral Rescue Therapy (ORT), Corticosteroid, or Bailout Rilonacept for Pericarditis Every 4 Weeks Cumulatively in the RW Period

Timepoint [27]

RW Period (mean 24.8 weeks)

Secondary outcome [28]

Percentage of Participants Using ORT for Pericarditis in the First 24 Weeks of RW Period

Timepoint [28]

RW Period (up to Week 24)

Secondary outcome [29]

Percentage of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion on Magnetic Resonance Imaging (MRI) at RW Week 24

Timepoint [29]

RW Period Week 24

Secondary outcome [30]

Time From First Dose to Pain Response in the RI Period

Timepoint [30]

RI Period (up to 12 weeks)

Secondary outcome [31]

Time From First Dose to CRP Normalization in the RI Period

Timepoint [31]

RI Period (up to 12 weeks)

Secondary outcome [32]

Time From First Dose to Rilonacept Monotherapy in RI Period

Timepoint [32]

RI Period (up to 12 weeks)

Secondary outcome [33]

Time From First Dose to Treatment Response in RI Period

Timepoint [33]

RI Period (up to 12 weeks)

Secondary outcome [34]

Percentage of Participants Achieving Clinical Response at RI Period Week 12

Timepoint [34]

RI Period Week 12

Secondary outcome [35]

Percentage of Participants With CRP Normalization at RI Period Week 12

Timepoint [35]

RI Period Week 12

Secondary outcome [36]

Change From Baseline Over Time in Weekly Average of Pericarditis Pain NRS Score in RI Period

Timepoint [36]

RI Period Baseline, RI Period Weeks 1-12

Secondary outcome [37]

Change From Baseline Over Time in CRP Levels in RI Period

Timepoint [37]

RI Period Baseline, RI Period Day 4, Weeks 1, 2, 4, 6, 12

Secondary outcome [38]

Percentage of Participants With Resolution of Pericarditis-Related ECHO and ECG Abnormalities at Week 12 of the RI Period

Timepoint [38]

RI Period Baseline, RI Period Week 12

Secondary outcome [39]

Percentage of Days With No or Minimal Pain in the RI Period While on Treatment

Timepoint [39]

RI Period (up to Week 12)

Secondary outcome [40]

Percentage of Participants With No or Minimal Pericarditis Symptoms Over Time in the RI Period, Based on the PGIPS

Timepoint [40]

RI Period Baseline, RI Period Weeks 6 and 12

Secondary outcome [41]

Percentage of Participants With No or Minimal Pericarditis Activity Over Time in the RI Period, Based on the PGA-PA

Timepoint [41]

RI Period Baseline, RI Period Weeks 6 and 12

Secondary outcome [42]

Change From RI Period Baseline in the SF-36 Domain Scores and Physical and Mental Scores to RI Period Week 12

Timepoint [42]

RI Period Baseline, RI Period Week 12

Secondary outcome [43]

Change From RI Period Baseline in SF-6D Scores at RI Period Week 12

Timepoint [43]

RI Period Baseline, RI Period Week 12

Secondary outcome [44]

Change From RI Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value at RI Period Week 12

Timepoint [44]

RI Period Baseline, RI Period Week 12

Secondary outcome [45]

Change From RI Period Baseline in ISI Total Score at RI Period Week 12

Timepoint [45]

RI Period Baseline, RI Period Week 12

Secondary outcome [46]

Change in ISI Categories From RI Period Baseline to RI Period Week 12

Timepoint [46]

RI Period Baseline (BL), RI Period Week (Wk) 12

Secondary outcome [47]

Number of Participants Who Were Off Background Pericarditis Medication on or Before RI Period Weeks 4, 8, 10, and 12

Timepoint [47]

RI Period Baseline, RI Period Weeks 4, 8, 10, 12

Secondary outcome [48]

Annualized Rate of Pericarditis Recurrence in the Long-Term Extension (LTE) Period Based on Investigator's Assessment (Based on Investigators' Judgement)

Timepoint [48]

LTE Period, through LTE Follow up (up to Week 48)

Secondary outcome [49]

Change From LTE Baseline Over Time in CRP Levels

Timepoint [49]

LTE Baseline, LTE Week 12, LTE Week 24

Secondary outcome [50]

Percentage of Participants With Absent or Minimal Pericarditis Activity In the LTE Period Based on the PGIPS

Timepoint [50]

LTE Baseline, LTE Month 12, LTE Month 24

Secondary outcome [51]

Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the LTE Period Based on the PGA-PA

Timepoint [51]

LTE Baseline, LTE Week 12, LTE Week 24

Secondary outcome [52]

Change From LTE Baseline in the SF-36 Domain Scores and Physical and Mental Scores

Timepoint [52]

LTE Baseline, LTE Week 24

Secondary outcome [53]

Change From LTE Baseline in SF-6D Health Utility Index Score

Timepoint [53]

LTE Baseline, LTE Week 24

Secondary outcome [54]

Change From LTE Baseline in EQ-5D-5L Individual Scores and Index Value

Timepoint [54]

LTE Baseline, LTE Week 24

Secondary outcome [55]

Change From LTE Baseline in ISI Total Score

Timepoint [55]

LTE Baseline, LTE Week 24

Secondary outcome [56]

Change From LTE Baseline in ISI Categories

Timepoint [56]

LTE Baseline (BL), LTE Week 24

Secondary outcome [57]

Percentage of Participants Requiring Addition of Standard of Care (SOC) Pericarditis Therapy Every 4 Weeks Cumulatively in the LTE Period

Timepoint [57]

LTE Period, through LTE Follow up (up to Week 24)

Secondary outcome [58]

Change From LTE Baseline in Pericardial Signs in ECHO

Timepoint [58]

LTE Baseline, LTE Week 24

Secondary outcome [59]

Change From LTE Baseline in Pericardial Signs in ECG

Timepoint [59]

LTE Baseline, LTE Week 24

Secondary outcome [60]

Change From LTE Baseline in Pericardial Signs in MRI

Timepoint [60]

LTE Baseline, LTE Week 24

Secondary outcome [61]

Number of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion at LTE Period Week 24

Timepoint [61]

LTE Week 24

Secondary outcome [62]

Annualized Rate of Pericarditis Recurrence in LTE Periods Based on Investigator's Assessment

Timepoint [62]

LTE Period, through LTE Follow up (up to Week 48)

Secondary outcome [63]

Annualized Rate of Pericarditis Recurrence in RW Period Based on CEC Adjudication

Timepoint [63]

RW Period (mean 24.8 weeks)

Eligibility

Key inclusion criteria

Key

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.

Key

Minimum age

12 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key 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.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

7/01/2019

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

30/06/2022

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD,VIC

Recruitment hospital [1]

HeartCare Partners Clinical Research Unit - Milton

Recruitment hospital [2]

GenesisCare - Cardiology Research - Doncaster East

Recruitment postcode(s) [1]

40664 - Milton

Recruitment postcode(s) [2]

3109 - Doncaster East

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

Georgia

Country [3]

United States of America

State/province [3]

Illinois

Country [4]

United States of America

State/province [4]

Minnesota

Country [5]

United States of America

State/province [5]

Ohio

Country [6]

United States of America

State/province [6]

Pennsylvania

Country [7]

United States of America

State/province [7]

Utah

Country [8]

United States of America

State/province [8]

Vermont

Country [9]

United States of America

State/province [9]

Virginia

Country [10]

United States of America

State/province [10]

Washington

Country [11]

Israel

State/province [11]

Haifa

Country [12]

Israel

State/province [12]

Jerusalem

Country [13]

Israel

State/province [13]

Nahariya

Country [14]

Israel

State/province [14]

Ramat Gan

Country [15]

Italy

State/province [15]

Lazio

Country [16]

Italy

State/province [16]

Lombardy

Country [17]

Italy

State/province [17]

Piedmont

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Kiniksa Pharmaceuticals (UK), Ltd.

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

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

Trial website

https://clinicaltrials.gov/study/NCT03737110

Trial related presentations / publications

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.
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. Erratum In: Heart. 2023 Dec 20;110(2):e1. doi: 10.1136/heartjnl-2022-321328corr1.
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.
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.

Public notes

Contacts

Principal investigator

Name

Clinical Operations Study Director

Address

Kiniksa Pharmaceuticals (UK), Ltd.

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03737110

Trial Review

Registering a new trial?

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03737110