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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

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] 0 0
2018-002719-87
Secondary ID [2] 0 0
KPL-914-C002
Universal Trial Number (UTN)
Trial acronym
RHAPSODY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Pericarditis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Other 0 0 0 0
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] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Pericarditis Recurrence in the RW Period
Timepoint [1] 0 0
RW Period (mean 24.8 weeks)
Secondary outcome [1] 0 0
Major Secondary Efficacy Endpoint: Percentage of Participants Who Maintained Clinical Response at Week 16 of the RW Period
Timepoint [1] 0 0
RW Period Week 16
Secondary outcome [2] 0 0
Major Secondary Efficacy Endpoint: Percentage of Days With No or Minimal Pericarditis Pain at Week 16 of the RW Period
Timepoint [2] 0 0
RW Period Week 16
Secondary outcome [3] 0 0
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] 0 0
RW Period Week 16
Secondary outcome [4] 0 0
Percentage of Participants Who Maintained Clinical Response at Week 24 of the RW Period
Timepoint [4] 0 0
RW Period Week 24
Secondary outcome [5] 0 0
Percentage of Participants Who Maintained Clinical Response at Week 8 of the RW Period
Timepoint [5] 0 0
RW Period Week 8
Secondary outcome [6] 0 0
Percentage of Days With No or Minimal Pericarditis Pain at Week 24 of the RW Period
Timepoint [6] 0 0
RW Period Week 24
Secondary outcome [7] 0 0
Percentage of Days With No or Minimal Pericarditis Pain at Week 8 of the RW Period
Timepoint [7] 0 0
RW Period Week 8
Secondary outcome [8] 0 0
Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 24 of the RW Period Based on the PGIPS
Timepoint [8] 0 0
RW Period Week 24
Secondary outcome [9] 0 0
Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 8 of the RW Period Based on the PGIPS
Timepoint [9] 0 0
RW Period Week 8
Secondary outcome [10] 0 0
Percentage of Participants Without Pericarditis Recurrence in the First 24 Weeks of the RW Period
Timepoint [10] 0 0
up to 24 weeks in the RW Period
Secondary outcome [11] 0 0
Time to Pericarditis Pain = 4 on the NRS in the RW Period
Timepoint [11] 0 0
RW Period (mean 24.8 weeks)
Secondary outcome [12] 0 0
Time to CRP Level = 1 mg/dL in the RW Period
Timepoint [12] 0 0
RW Period (mean 24.8 weeks)
Secondary outcome [13] 0 0
Time to Pericardial Rub in the RW Period
Timepoint [13] 0 0
RW Period (mean 24.8 weeks)
Secondary outcome [14] 0 0
Time to Widespread ST-segment Elevation or PR-segment Depression on Electrocardiogram (ECG) in the RW Period
Timepoint [14] 0 0
RW Period (mean 24.8 weeks)
Secondary outcome [15] 0 0
Time to New or Worsening Pericardial Effusion on Echocardiography (ECHO) in the RW Period
Timepoint [15] 0 0
RW Period (mean 24.8 weeks)
Secondary outcome [16] 0 0
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] 0 0
RW Period Baseline, RW Period Week 24, RW Period (mean 24.8 weeks)
Secondary outcome [17] 0 0
Change From RW Period Baseline Over Time in CRP Levels in RW Period
Timepoint [17] 0 0
RW Period Baseline, RW Period Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 56
Secondary outcome [18] 0 0
Change From RW Period Baseline Over Time in Weekly Average of Pericarditis Pain in the RW Period
Timepoint [18] 0 0
RW Period Baseline, RW Period Weeks 1-50, 54
Secondary outcome [19] 0 0
Percentage of Participants With Absent or Minimal Pericarditis Symptoms Over Time After RW Period Week 24 Based on the PGIPS
Timepoint [19] 0 0
RW Period Weeks 32, 40, 48, 56
Secondary outcome [20] 0 0
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] 0 0
RW Period Baseline, RW Period Weeks 8, 16, 24, 32, 40, 48, 56
Secondary outcome [21] 0 0
Change From RW Period Baseline in Short Form-36 (SF-36) Physical and Mental Component Scores at RW Period Week 24
Timepoint [21] 0 0
RW Period Baseline, RW Period Week 24
Secondary outcome [22] 0 0
Change From RW Baseline in SF-36 Individual Scores at RW Period Week 24
Timepoint [22] 0 0
RW Period Baseline, RW Period Week 24
Secondary outcome [23] 0 0
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] 0 0
RW Period Baseline, RW Period Week 24
Secondary outcome [24] 0 0
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] 0 0
RW Period Baseline, RW Period Week 24
Secondary outcome [25] 0 0
Change From RW Period Baseline in Insomnia Severity Index (ISI) Total Score at RW Period Week 24
Timepoint [25] 0 0
RW Period Baseline, RW Period Week 24
Secondary outcome [26] 0 0
Change in ISI Categories From RW Period Baseline to RW Period Week 24
Timepoint [26] 0 0
RW Period Baseline (BL), RW Period Week (Wk) 24
Secondary outcome [27] 0 0
Percentage of Participants Using Oral Rescue Therapy (ORT), Corticosteroid, or Bailout Rilonacept for Pericarditis Every 4 Weeks Cumulatively in the RW Period
Timepoint [27] 0 0
RW Period (mean 24.8 weeks)
Secondary outcome [28] 0 0
Percentage of Participants Using ORT for Pericarditis in the First 24 Weeks of RW Period
Timepoint [28] 0 0
RW Period (up to Week 24)
Secondary outcome [29] 0 0
Percentage of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion on Magnetic Resonance Imaging (MRI) at RW Week 24
Timepoint [29] 0 0
RW Period Week 24
Secondary outcome [30] 0 0
Time From First Dose to Pain Response in the RI Period
Timepoint [30] 0 0
RI Period (up to 12 weeks)
Secondary outcome [31] 0 0
Time From First Dose to CRP Normalization in the RI Period
Timepoint [31] 0 0
RI Period (up to 12 weeks)
Secondary outcome [32] 0 0
Time From First Dose to Rilonacept Monotherapy in RI Period
Timepoint [32] 0 0
RI Period (up to 12 weeks)
Secondary outcome [33] 0 0
Time From First Dose to Treatment Response in RI Period
Timepoint [33] 0 0
RI Period (up to 12 weeks)
Secondary outcome [34] 0 0
Percentage of Participants Achieving Clinical Response at RI Period Week 12
Timepoint [34] 0 0
RI Period Week 12
Secondary outcome [35] 0 0
Percentage of Participants With CRP Normalization at RI Period Week 12
Timepoint [35] 0 0
RI Period Week 12
Secondary outcome [36] 0 0
Change From Baseline Over Time in Weekly Average of Pericarditis Pain NRS Score in RI Period
Timepoint [36] 0 0
RI Period Baseline, RI Period Weeks 1-12
Secondary outcome [37] 0 0
Change From Baseline Over Time in CRP Levels in RI Period
Timepoint [37] 0 0
RI Period Baseline, RI Period Day 4, Weeks 1, 2, 4, 6, 12
Secondary outcome [38] 0 0
Percentage of Participants With Resolution of Pericarditis-Related ECHO and ECG Abnormalities at Week 12 of the RI Period
Timepoint [38] 0 0
RI Period Baseline, RI Period Week 12
Secondary outcome [39] 0 0
Percentage of Days With No or Minimal Pain in the RI Period While on Treatment
Timepoint [39] 0 0
RI Period (up to Week 12)
Secondary outcome [40] 0 0
Percentage of Participants With No or Minimal Pericarditis Symptoms Over Time in the RI Period, Based on the PGIPS
Timepoint [40] 0 0
RI Period Baseline, RI Period Weeks 6 and 12
Secondary outcome [41] 0 0
Percentage of Participants With No or Minimal Pericarditis Activity Over Time in the RI Period, Based on the PGA-PA
Timepoint [41] 0 0
RI Period Baseline, RI Period Weeks 6 and 12
Secondary outcome [42] 0 0
Change From RI Period Baseline in the SF-36 Domain Scores and Physical and Mental Scores to RI Period Week 12
Timepoint [42] 0 0
RI Period Baseline, RI Period Week 12
Secondary outcome [43] 0 0
Change From RI Period Baseline in SF-6D Scores at RI Period Week 12
Timepoint [43] 0 0
RI Period Baseline, RI Period Week 12
Secondary outcome [44] 0 0
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] 0 0
RI Period Baseline, RI Period Week 12
Secondary outcome [45] 0 0
Change From RI Period Baseline in ISI Total Score at RI Period Week 12
Timepoint [45] 0 0
RI Period Baseline, RI Period Week 12
Secondary outcome [46] 0 0
Change in ISI Categories From RI Period Baseline to RI Period Week 12
Timepoint [46] 0 0
RI Period Baseline (BL), RI Period Week (Wk) 12
Secondary outcome [47] 0 0
Number of Participants Who Were Off Background Pericarditis Medication on or Before RI Period Weeks 4, 8, 10, and 12
Timepoint [47] 0 0
RI Period Baseline, RI Period Weeks 4, 8, 10, 12
Secondary outcome [48] 0 0
Annualized Rate of Pericarditis Recurrence in the Long-Term Extension (LTE) Period Based on Investigator's Assessment (Based on Investigators' Judgement)
Timepoint [48] 0 0
LTE Period, through LTE Follow up (up to Week 48)
Secondary outcome [49] 0 0
Change From LTE Baseline Over Time in CRP Levels
Timepoint [49] 0 0
LTE Baseline, LTE Week 12, LTE Week 24
Secondary outcome [50] 0 0
Percentage of Participants With Absent or Minimal Pericarditis Activity In the LTE Period Based on the PGIPS
Timepoint [50] 0 0
LTE Baseline, LTE Month 12, LTE Month 24
Secondary outcome [51] 0 0
Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the LTE Period Based on the PGA-PA
Timepoint [51] 0 0
LTE Baseline, LTE Week 12, LTE Week 24
Secondary outcome [52] 0 0
Change From LTE Baseline in the SF-36 Domain Scores and Physical and Mental Scores
Timepoint [52] 0 0
LTE Baseline, LTE Week 24
Secondary outcome [53] 0 0
Change From LTE Baseline in SF-6D Health Utility Index Score
Timepoint [53] 0 0
LTE Baseline, LTE Week 24
Secondary outcome [54] 0 0
Change From LTE Baseline in EQ-5D-5L Individual Scores and Index Value
Timepoint [54] 0 0
LTE Baseline, LTE Week 24
Secondary outcome [55] 0 0
Change From LTE Baseline in ISI Total Score
Timepoint [55] 0 0
LTE Baseline, LTE Week 24
Secondary outcome [56] 0 0
Change From LTE Baseline in ISI Categories
Timepoint [56] 0 0
LTE Baseline (BL), LTE Week 24
Secondary outcome [57] 0 0
Percentage of Participants Requiring Addition of Standard of Care (SOC) Pericarditis Therapy Every 4 Weeks Cumulatively in the LTE Period
Timepoint [57] 0 0
LTE Period, through LTE Follow up (up to Week 24)
Secondary outcome [58] 0 0
Change From LTE Baseline in Pericardial Signs in ECHO
Timepoint [58] 0 0
LTE Baseline, LTE Week 24
Secondary outcome [59] 0 0
Change From LTE Baseline in Pericardial Signs in ECG
Timepoint [59] 0 0
LTE Baseline, LTE Week 24
Secondary outcome [60] 0 0
Change From LTE Baseline in Pericardial Signs in MRI
Timepoint [60] 0 0
LTE Baseline, LTE Week 24
Secondary outcome [61] 0 0
Number of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion at LTE Period Week 24
Timepoint [61] 0 0
LTE Week 24
Secondary outcome [62] 0 0
Annualized Rate of Pericarditis Recurrence in LTE Periods Based on Investigator's Assessment
Timepoint [62] 0 0
LTE Period, through LTE Follow up (up to Week 48)
Secondary outcome [63] 0 0
Annualized Rate of Pericarditis Recurrence in RW Period Based on CEC Adjudication
Timepoint [63] 0 0
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?
No
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
HeartCare Partners Clinical Research Unit - Milton
Recruitment hospital [2] 0 0
GenesisCare - Cardiology Research - Doncaster East
Recruitment postcode(s) [1] 0 0
40664 - Milton
Recruitment postcode(s) [2] 0 0
3109 - Doncaster East
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
United States of America
State/province [8] 0 0
Vermont
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Israel
State/province [11] 0 0
Haifa
Country [12] 0 0
Israel
State/province [12] 0 0
Jerusalem
Country [13] 0 0
Israel
State/province [13] 0 0
Nahariya
Country [14] 0 0
Israel
State/province [14] 0 0
Ramat Gan
Country [15] 0 0
Italy
State/province [15] 0 0
Lazio
Country [16] 0 0
Italy
State/province [16] 0 0
Lombardy
Country [17] 0 0
Italy
State/province [17] 0 0
Piedmont

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kiniksa Pharmaceuticals (UK), Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Operations Study Director
Address 0 0
Kiniksa Pharmaceuticals (UK), Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.