A Pilot Study of KPL-914 in Recurrent Pericarditis

Recurrent Pericarditis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03980522
• Other study ID #: KPL-914-C001
• Status: Completed
• Phase: Phase 2
• Start date: January 24, 2018
• Est. completion date: May 17, 2019

Study information

• Verified date: May 2021
• Source: Kiniksa Pharmaceuticals, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: May 17, 2019
• Est. primary completion date: May 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pericarditis
• Recurrent Pericarditis

Intervention

Drug:
• KPL-914
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.

Locations

Country	Name	City	State
United States	Ellipsis Research Group	Brooklyn	New York
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Cleveland Clinic	Cleveland	Ohio
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	BI Research Center	Houston	Texas
United States	Franciscan Physician Network Indiana Heart Physicians Cardiovascular Research Program	Indianapolis	Indiana
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	Affinity Clinical Research Institute	Oak Brook	Illinois
United States	Research Integrity, LLC	Owensboro	Kentucky
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Swedish Medical Center	Seattle	Washington
United States	Medstar Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Kiniksa Pharmaceuticals (UK), Ltd.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Klein AL, Lin D, Cremer PC, Nasir S, Luis SA, Abbate A, Ertel A, LeWinter M, Beutler A, Fang F, Paolini JF. Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial. Heart. 2020 Nov 23. pii: heartjnl-2020-317928 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)