Clinical trial NCT03980522: A Pilot Study of KPL-914 in Recurrent Pericarditis
Official title: An Open-Label Pilot Study of KPL-914 in Recurrent Pericarditis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Pericarditis
Lead sponsor: Kiniksa Pharmaceuticals International, plc
Sponsor class: INDUSTRY
First posted: 2019-06-10
Enrollment: 26
Sex: ALL
Minimum age (years): 6
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Parts 1, 2 and 4: Pretreatment C-Reactive Protein (CRP) Levels
timeFrame: 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)
measure: Parts 1, 2 and 4: On-Treatment Change From Baseline Over Time in CRP Levels
timeFrame: 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)
measure: Parts 1, 2 and 4: Pretreatment Pain NRS Scores
timeFrame: 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)
measure: Parts 1, 2 and 4: On-Treatment Change From Baseline Over Time in Pain NRS Scores
timeFrame: 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)
measure: Parts 3 and 5: Change From Baseline Over Time in CRP Levels
timeFrame: 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)
measure: Parts 3 and 5: Change From Baseline Over Time in Pain NRS Scores
timeFrame: 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)
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Oak Brook
country: United States
facility: Affinity Clinical Research Institute
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan Physician Network Indiana Heart Physicians Cardiovascular Research Program
state: Indiana
city: Owensboro
country: United States
facility: Research Integrity, LLC
state: Kentucky
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Brooklyn
country: United States
facility: Ellipsis Research Group
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: BI Research Center
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: Kiniksa Pharmaceuticals (UK), Ltd.
name: Clinical Operations Study Director
role: STUDY_DIRECTOR
References:
citation: 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;107(6):488-96. doi: 10.1136/heartjnl-2020-317928. Online ahead of print.
citation: Lin D, Klein A, Cella D, Beutler A, Fang F, Magestro M, Cremer P, LeWinter MM, Luis SA, Abbate A, Ertel A, Litcher-Kelly L, Klooster B, Paolini JF. Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept. BMC Cardiovasc Disord. 2021 Apr 21;21(1):201. doi: 10.1186/s12872-021-02008-3.