Phase 3
N=86
Study to Assess the Efficacy and Safety of Rilonacept Treatment in Participants With Recurrent Pericarditis
Recurrent Pericarditis
Bottom Line
View on ClinicalTrials.gov: NCT03737110 ↗Enrolled (actual)
86
Serious AEs
4.6%
Results posted
Jul 2021
Primary outcome: Primary: Time to Pericarditis Recurrence in the RW Period — NA; 8.6 weeks — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Rilonacept (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Kiniksa Pharmaceuticals (UK), Ltd.
- Primary completion
- May 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Pericarditis Recurrence in the RW Period |
NA; 8.6 | <0.0001 sig |
| SECONDARY Major Secondary Efficacy Endpoint: Percentage of Participants Who Maintained Clinical Response at Week 16 of the RW Period |
81.0; 20.0 | 0.0002 sig |
| SECONDARY Major Secondary Efficacy Endpoint: Percentage of Days With No or Minimal Pericarditis Pain at Week 16 of the RW Period |
98.6; 47.4 | < 0.0001 sig |
| SECONDARY 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 |
81.0; 25.0 | 0.0006 sig |
| SECONDARY Percentage of Participants Who Maintained Clinical Response at Week 24 of the RW Period |
76.5; 20.0 | 0.0022 sig |
| SECONDARY Percentage of Participants Who Maintained Clinical Response at Week 8 of the RW Period |
77.8; 25.8 | < 0.0001 sig |
| SECONDARY Percentage of Days With No or Minimal Pericarditis Pain at Week 24 of the RW Period |
100.6; 48.7 | < 0.0001 sig |
| SECONDARY Percentage of Days With No or Minimal Pericarditis Pain at Week 8 of the RW Period |
97.9; 57.3 | < 0.0001 sig |
| SECONDARY Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 24 of the RW Period Based on the PGIPS |
88.2; 20.0 | 0.0002 sig |
| SECONDARY Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 8 of the RW Period Based on the PGIPS |
85.2; 32.3 | < 0.0001 sig |
| SECONDARY Percentage of Participants Without Pericarditis Recurrence in the First 24 Weeks of the RW Period |
95.7; 19.9 | < 0.0001 sig |
| SECONDARY Time to Pericarditis Pain ≥ 4 on the NRS in the RW Period |
NA; 4.1 | < 0.0001 sig |
| SECONDARY Time to CRP Level ≥ 1 mg/dL in the RW Period |
NA; 6.9 | < 0.0001 sig |
| SECONDARY Time to Pericardial Rub in the RW Period |
NA; NA | 0.7447 |
| SECONDARY Time to Widespread ST-segment Elevation or PR-segment Depression on Electrocardiogram (ECG) in the RW Period |
NA; NA | 0.2066 |
| SECONDARY Time to New or Worsening Pericardial Effusion on Echocardiography (ECHO) in the RW Period |
NA; NA | 0.0059 sig |
| SECONDARY Number of Participants in ECHO Pericardial Effusion Size Categories at RW Period Baseline, RW Week 24 and Worst Post-baseline in the RW Period |
28; 28; 30; 30; 1; 1 | — |
| SECONDARY Change From RW Period Baseline Over Time in CRP Levels in RW Period |
-0.01; -0.05; 0.15; 1.46; 0.12; 0.11 | — |
| SECONDARY Change From RW Period Baseline Over Time in Weekly Average of Pericarditis Pain in the RW Period |
-0.08; -0.08; 0.17; 0.17; -0.21; -0.25 | — |
| SECONDARY Percentage of Participants With Absent or Minimal Pericarditis Symptoms Over Time After RW Period Week 24 Based on the PGIPS |
90.9; 83.3; 50.0; 70.0; 60.0; 66.7 | — |
| SECONDARY 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) |
96.7; 96.7; 100; 100; 100; 100 | — |
| SECONDARY Change From RW Period Baseline in Short Form-36 (SF-36) Physical and Mental Component Scores at RW Period Week 24 |
0.427; 0.427; 0.363; 0.354; 3.081; 3.081 | — |
| SECONDARY Change From RW Baseline in SF-36 Individual Scores at RW Period Week 24 |
2.427; 2.427; -0.637; 0.273; 2.995; 2.995 | — |
| SECONDARY Change From RW Period Baseline in the Short Form Health Survey-6 Domains (SF-6D) Utility Index Score at RW Period Week 24 |
0.0385; 0.0385; -0.0027; -0.0005 | — |
| SECONDARY Change From RW Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value to RW Period Week 24 |
-0.1; -0.1; 0.0; -0.1; -0.1; -0.1 | — |
| SECONDARY Change From RW Period Baseline in Insomnia Severity Index (ISI) Total Score at RW Period Week 24 |
-0.7; -0.7; -0.3; -0.2 | — |
| SECONDARY Change in ISI Categories From RW Period Baseline to RW Period Week 24 |
7; 7; 2; 9; 3; 3 | — |
| SECONDARY Percentage of Participants Using Oral Rescue Therapy (ORT), Corticosteroid, or Bailout Rilonacept for Pericarditis Every 4 Weeks Cumulatively in the RW Period |
0; 3.2; 0; 6.5; 0; 6.5 | < 0.0001 sig |
| SECONDARY Percentage of Participants Using ORT for Pericarditis in the First 24 Weeks of RW Period |
3.3; 6.5 | — |
| SECONDARY Percentage of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion on Magnetic Resonance Imaging (MRI) at RW Week 24 |
66.7; 66.7; 28.6; 57.1; 0; 0 | — |
| SECONDARY Time From First Dose to Pain Response in the RI Period |
5.0 | — |
| SECONDARY Time From First Dose to CRP Normalization in the RI Period |
7.0 | — |
| SECONDARY Time From First Dose to Rilonacept Monotherapy in RI Period |
7.3 | — |
| SECONDARY Time From First Dose to Treatment Response in RI Period |
5.0 | — |
| SECONDARY Percentage of Participants Achieving Clinical Response at RI Period Week 12 |
84.9; 15.1 | — |
| SECONDARY Percentage of Participants With CRP Normalization at RI Period Week 12 |
98.6 | — |
| SECONDARY Change From Baseline Over Time in Weekly Average of Pericarditis Pain NRS Score in RI Period |
4.48; -2.31; -3.18; -3.28; -3.51; -3.55 | — |
| SECONDARY Change From Baseline Over Time in CRP Levels in RI Period |
3.72; -2.80; -3.48; -3.55; -3.46; -3.55 | — |
| SECONDARY Percentage of Participants With Resolution of Pericarditis-Related ECHO and ECG Abnormalities at Week 12 of the RI Period |
63.6; 100; 100 | — |
| SECONDARY Percentage of Days With No or Minimal Pain in the RI Period While on Treatment |
80.66 | — |
| SECONDARY Percentage of Participants With No or Minimal Pericarditis Symptoms Over Time in the RI Period, Based on the PGIPS |
18.1; 89.5; 92.6 | — |
| SECONDARY Percentage of Participants With No or Minimal Pericarditis Activity Over Time in the RI Period, Based on the PGA-PA |
10.6; 94.8; 98.7 | — |
| SECONDARY Change From RI Period Baseline in the SF-36 Domain Scores and Physical and Mental Scores to RI Period Week 12 |
13.8; 9.2; 10.1; 13.8; 19.1; 7.7 | — |
| SECONDARY Change From RI Period Baseline in SF-6D Scores at RI Period Week 12 |
0.1828 | — |
| SECONDARY Change From RI Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value at RI Period Week 12 |
-0.2; -0.1; -1.1; -1.5; -0.5; 0.1626 | — |
| SECONDARY Change From RI Period Baseline in ISI Total Score at RI Period Week 12 |
-4.9 | — |
| SECONDARY Change in ISI Categories From RI Period Baseline to RI Period Week 12 |
23; 1; 1; 0; 1; 18 | — |
| SECONDARY Number of Participants Who Were Off Background Pericarditis Medication on or Before RI Period Weeks 4, 8, 10, and 12 |
7; 79; 15; 69; 49; 32 | — |
| SECONDARY Annualized Rate of Pericarditis Recurrence in the Long-Term Extension (LTE) Period Based on Investigator's Assessment (Based on Investigators' Judgement) |
0.088; 0.168; 0.125; 0.132 | — |
| SECONDARY Change From LTE Baseline Over Time in CRP Levels |
0.18; 0.21; 0.16; 0.18; 0.01; 0.00 | — |
| SECONDARY Percentage of Participants With Absent or Minimal Pericarditis Activity In the LTE Period Based on the PGIPS |
100.0; 88.0; 91.2; 91.9; 93.3; 95.8 | — |
| SECONDARY Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the LTE Period Based on the PGA-PA |
100.0; 92.0; 94.1; 94.6; 100.0; 91.7 | — |
| SECONDARY Change From LTE Baseline in the SF-36 Domain Scores and Physical and Mental Scores |
2.596; 0.125; -0.463; 0.391; -1.443; 2.052 | — |
| SECONDARY Change From LTE Baseline in SF-6D Health Utility Index Score |
-0.106; 0.163; 0.003; 0.035 | — |
| SECONDARY Change From LTE Baseline in EQ-5D-5L Individual Scores and Index Value |
-0.2; 0.0; 0.1; 0.0; 0.1; -0.1 | — |
| SECONDARY Change From LTE Baseline in ISI Total Score |
-0.3; -0.2; -1.1; -0.1 | — |
| SECONDARY Change From LTE Baseline in ISI Categories |
9; 11; 18; 38; 1; 2 | — |
| SECONDARY Percentage of Participants Requiring Addition of Standard of Care (SOC) Pericarditis Therapy Every 4 Weeks Cumulatively in the LTE Period |
— | — |
| SECONDARY Change From LTE Baseline in Pericardial Signs in ECHO |
3; 4; 7; 14; 0; 0 | — |
| SECONDARY Change From LTE Baseline in Pericardial Signs in ECG |
7; 16; 21; 44; 0; 1 | — |
| SECONDARY Change From LTE Baseline in Pericardial Signs in MRI |
2; 5; 2; 9; 1; 1 | — |
| SECONDARY Number of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion at LTE Period Week 24 |
2; 5; 2; 9; 1; 1 | — |
| SECONDARY Annualized Rate of Pericarditis Recurrence in LTE Periods Based on Investigator's Assessment |
0.088; 0.168; 0.125; 0.132 | — |
| SECONDARY Annualized Rate of Pericarditis Recurrence in RW Period Based on CEC Adjudication |
0.137 | — |
Summary
The primary objective of this study was to assess the efficacy of rilonacept treatment in participants with recurrent pericarditis.
Eligibility Criteria
Key Inclusion Criteria
- 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.
Key Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT03737110). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.