A Pilot Study of KPL-914 in Recurrent Pericarditis

Study Overview
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Brief Summary
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The purpose of this study is to assess the preliminary efficacy and safety of KPL-914 treatment in participants with recurrent pericarditis.

Detailed Description
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This is an open-label, single-arm pilot study to explore clinical and biochemical endpoints of pericarditis symptomatology and to collect data to assess inter- and intra-subject variability on both at-baseline and on-treatment parameters. This study consists of 5 distinct Parts, and all participants will be treated with once-weekly subcutaneously (SC)-administered injections of KPL-914.There is an optional 18-week extension period.

Official Title
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An Open-Label Pilot Study of KPL-914 in Recurrent Pericarditis

Conditions
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Recurrent Pericarditis

Intervention / Treatment
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* Drug: KPL-914


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for All Participants: Has given consent (or assent, if applicable) and signed an Informed Consent Form (ICF) (or informed assent form, if applicable). Male or female, of any ethnic origin. 6 to 75 years of age, inclusive. If used, has received non-steroidal anti-inflammatory drugs (NSAIDs), and/or colchicine and/or corticosteroids (in any combination) at stable dose levels for at least 7 days prior to study drug dosing (although stable doses for a shorter period will be acceptable if in the opinion of the Investigator, in consultation with the Sponsor, a shorter period of stability is not anticipated to alter the baseline CRP values) and is anticipated to continue these concomitant medications at these dose levels for the duration of the active Treatment Period. If female of child-bearing potential, must be nonpregnant and nonlactating and must agree to use an effective method of contraception, e.g., hormonal contraception or double-barrier birth control. Is able to adequately maintain a medication diary. Agrees to refrain from making any new, major life-style changes that may affect pericarditis symptoms (e.g., starting a new diet or changing exercise pattern) from the time of signature of the ICF (or informed assent form, if applicable) to the End-of-Trial Visit. Parts 1, 2 and 4: Subjects eligible for Parts 1, 2 and 4 have to present during a symptomatic episode of recurrent idiopathic pericarditis (RIP; Parts 1 and 2) and post pericardiotomy syndrome (PPS; Part 4) and a history of at least one pericarditis recurrence. They can be enrolled into Part 1 or 4 if the CRP value at screening is >1 mg/dL, and into Part 2 if a CRP ≤1 mg/dL (attributed to concomitant medications e.g., corticosteroids), and there is an evidence of pericardial inflammation on cardiac MRI confirmed by the imaging core lab. Enrollment into Part 3 and 5: Subjects eligible for Part 3 of this study have to present with corticosteroid-dependent RIP or PPS and history of at least 2 pericarditis recurrences. Exclusion Criteria for All Participants: Has a diagnosis of pericarditis that was secondary to specific excluded etiologies, including tuberculous, neoplastic, or purulent etiologies, post-myocardial infarction (early or late), thoracic trauma, myocarditis, or systemic diseases including autoinflammatory diseases, autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.). Has a history of immunodepression, including a positive human immunodeficiency virus test result. Has received treatment within the 6-month period before dosing with any systemic immunosuppressants (other than, for example, corticosteroids or mycophenolate) which, in the opinion of the Investigator (in consultation with the Sponsor), may interfere with the study endpoints. Currently receiving other interleukin (IL)-1 or IL-6 blockers, Janus-activating kinase (JAK) or tumor necrosis factor (TNF) inhibitors.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KPL-914: Part 1 Participants<br>Part 1 enrolls symptomatic participants with recurrent idiopathic pericarditis (RIP) with an elevated marker of systemic inflammation (C-reactive protein [CRP] > 1mg/dL). | Drug: KPL-914<br>* KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration. Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks. Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL. Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.<br>* Other names: rilonacept;|
| Experimental: KPL-914: Part 2 Participants<br>Part 2 enrolls symptomatic participants with RIP with CRP ≤1 mg/dL which, in the opinion of the Investigator, can be attributed to concomitant medications (e.g., corticosteroids) and with pericardial inflammation present on cardiac magnetic resonance imaging (MRI) confirmed by the imaging core lab. | Drug: KPL-914<br>* KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration. Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks. Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL. Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.<br>* Other names: rilonacept;|
| Experimental: KPL-914: Part 3 Participants<br>Part 3 enrolls participants with corticosteroid-dependent RIP not experiencing symptoms which would meet the diagnostic criteria for a flare of pericarditis. | Drug: KPL-914<br>* KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration. Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks. Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL. Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.<br>* Other names: rilonacept;|
| Experimental: KPL-914: Part 4 Participants<br>Part 4 enrolls symptomatic participants with recurrent post pericardiotomy syndrome (PPS) with an elevated marker of systemic inflammation (CRP > 1mg/dL). | Drug: KPL-914<br>* KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration. Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks. Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL. Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.<br>* Other names: rilonacept;|
| Experimental: KPL-914: Part 5 Participants<br>Part 5 enrolls participants with corticosteroid-dependent recurrent PPS not experiencing symptoms which would meet the diagnostic criteria for a flare of pericarditis. | Drug: KPL-914<br>* KPL-914 (rilonacept) will be provided in its commercially available formulation as a lyophilized powder to be reconstituted for SC administration. Adult participants (≥ 18 years of age) KPL-914 will be administered as an initial loading dose of 320 mg SC, delivered as 2 subcutaneous injections of 160 mg SC each on Day 0, then 160 mg SC dosed once weekly for 5 subsequent weeks. Pediatric participants (6 to <18 years of age) KPL-914 will be administered with an initial loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as 2 subcutaneous injections of 2.2 mg/kg each with a maximum single-injection volume of 2 mL. Participants considered to be 'treatment responders' will be offered participation in an optional 18-week extension period (EP) in which KPL-914 can be continued for a total duration of KPL-914 treatment of up to 24 weeks.<br>* Other names: rilonacept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1, 2 and 4: Pretreatment C-Reactive Protein (CRP) Levels |  | Screening Visit 1 (Day -3 to Day 0), Screening Visit 2 (Day -3 to Day 0), Day 0, Baseline (defined as the last non-missing assessment prior to the first study drug administration) | 
| Parts 1, 2 and 4: On-Treatment Change From Baseline Over Time in CRP Levels |  | Baseline, Treatment Period (TP) Weeks 2, 3, 4, 5, 6, TP Interval Evaluation (between Weeks 3-4), End of TP (up to Week 6), Extension Period (EP): Months 1, 2, 3, 4, EP Interval Evaluation (between Weeks 15-20), Final Visit (up to Week 25) | 
| Parts 1, 2 and 4: Pretreatment Pain NRS Scores | The average level of pericarditis pain over previous 24 hours was assessed by participants at each visit using 11-point pain NRS (where 0 indicates no pain and 10 indicates pain as bad as it could be). | Prescreening, Screening Visit 1 (Day -3 to Day 0), Screening Visit 2 (Day -3 to Day 0), Day 0, Baseline (defined as the last non-missing assessment prior to the first study drug administration) | 
| Parts 1, 2 and 4: On-Treatment Change From Baseline Over Time in Pain NRS Scores | The average level of pericarditis pain over previous 24 hours was assessed by participants at each visit using 11-point pain NRS (where 0 indicates no pain and 10 indicates pain as bad as it could be). | Baseline, Treatment Period (TP) Day 3, Weeks 2, 3, TP Interval Evaluation (between Weeks 3-4), 4, 5, 6, End of TP (up to Week 6), Extension Period (EP): Months 1, 2, 3, 4, EP Interval Evaluation (between Weeks 15-20), Final Visit (up to Week 25) | 
| Parts 3 and 5: Change From Baseline Over Time in CRP Levels | Baseline is defined as the last non-missing assessment prior to the first study drug administration. | Baseline, TP Weeks 2, 3, Interval Evaluation Visit (Weeks 3-4), 4, 5, 6, End of TP Visit (Week 6), EP Months 1, 2, 3, 4, EP Interval Evaluation Visit (Week 15-Week 20), Final Visit (up to EP Month 4) | 
| Parts 3 and 5: Change From Baseline Over Time in Pain NRS Scores | The average level of pericarditis pain over previous 24 hours was assessed by participants at each visit using 11-point pain NRS (where 0 indicates no pain and 10 indicates pain as bad as it could be). Baseline is defined as the last non-missing assessment prior to the first study drug administration. | Baseline, TP Day 3, TP Weeks 2, 3, Interval Evaluation Visit (Weeks 3-4), 4, 5, 6, End of TP Visit (Week 6), EP Months 1, 2, 3, 4, EP Interval Evaluation Visit (Week 15-Week 20), Final Visit (up to EP Month 4) |