Pericarditis, Pericarditis Acute, Recurrent Pericarditis
Conditions
Keywords
Recurrence, Recurrent, Recurrent Pericarditis, KPL-387
Brief summary
This study is being done to demonstrate whether KPL-387 is an effective and safe treatment for recurrent pericarditis.
Detailed description
This clinical trial is comprised of 3 separate study parts: Phase 2, Phase 3, and Long-Term Extension. The primary objective of Phase 2 is to evaluate how well different dose levels of KPL-387 control the pain and inflammation of pericarditis in a group of participants experiencing an acute episode of recurrent pericarditis. This part of the study will confirm the KPL-387 dose level to be further tested in Phase 3 and the Long-Term Extension. The primary objective of Phase 3 is to confirm the efficacy of KPL-387 for the treatment of recurrent pericarditis and reduction in risk of recurrence in an additional group of participants experiencing an acute episode of recurrent pericarditis. Participants who complete Phase 2 or Phase 3 may be eligible to participate in the Long-Term Extension. The primary objective of the Long-Term Extension is to assess the long-term efficacy of KPL-387 while maintaining long-term disease control. All of the study parts also have other objectives to learn about the safety, tolerability, concentration of KPL-387 in blood, and effects of KPL-387 on blood test markers of immune activity in recurrent pericarditis.
Interventions
DRUGKPL-387
administered by subcutaneous injection
DRUGPlacebo
administered by subcutaneous injection
Sponsors
Kiniksa Pharmaceuticals International, plc
Kiniksa Pharmaceuticals, GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Phase 2 and 3: Has a diagnosis of recurrent pericarditis * Phase 2 and 3: Has signs and symptoms of recurrent pericarditis despite treatment with standard therapies * Phase 2 and 3: Weighs at least 40 kg * Phase 2: Taking NSAIDS and/or colchicine (in any combination) * Phase 3: Taking NSAIDs and/or colchicine and/or glucocorticoids (in any combination) Key
Exclusion criteria
* Phase 2 and 3: Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies. * Phase 2 and 3: Has received an investigational drug during the 4 weeks before screening or is planning to receive an investigational drug at any time during the study. * Phase 2 and 3: Has a history of active or untreated, latent tuberculosis (TB) prior to screening. * Phase 2 and 3: Has a history of immunodeficiency. * Phase 2 and 3: Has a history of immunosuppression, including positive human immunodeficiency virus (HIV) test results. * Phase 2 and 3: Has chest x-ray at Screening or within 12 weeks before first study drug administration, with evidence of malignancy, abnormality consistent with prior or active TB infection or active infection. * Phase 2 and 3: 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). * Phase 2 and 3: Has a known or suspected current active infection or a history of chronic or recurrent infectious disease (\> 3 episodes in prior 12 months), including but not limited to, genitourinary infection, chest infection, sinusitis, or skin/soft tissue infection. * Phase 2 and 3: Has had a serious infection, has been admitted to the hospital for an infection, or has been treated for a documented infection requiring antibiotics for a documented infection within 2 weeks prior to first study drug administration. * Phase 2 and 3: Has had an organ transplant (except corneal transplant performed more than 3 months prior to first study drug administration). * Phase 2 and 3: In the Investigator's opinion, has any other medical condition that could adversely affect the subject's participation or interfere with study evaluations.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 3: Time to Pericarditis Recurrence | From Baseline in the RW Period |
| Long-Term Extension: Annualized rate of Pericarditis Recurrence | Up to 24 Months |
| Phase 2: Time to Treatment Response by Week 24 | From Baseline up to Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Phase 2: Percentage of Days With No or Minimal Pain (Numerical Rating Scale (NRS) ≤ 2) While on KPL-387 Treatment Over Time by Week 24 | From Baseline up to Week 24 |
| Phase 2: Proportion of Participants With Normalization of CRP (CRP ≤ 0.5 mg/dL) Over Time by Week 24 | From Baseline up to Week 24 |
| Phase 2: Time to resolution of pericarditis manifestations (i.e. echocardiogram [ECHO] abnormalities, electrocardiogram [ECG] abnormalities, and pericardial rub), when present at Baseline, by Week 16. | From Baseline up to Week 16 |
| Phase 2: Change from Baseline in SF-36v2® Physical Component Summary score through Week 24. | From Baseline up to Week 24 |
| Phase 2: Change from Baseline in SF-36v2® Mental Component Summary score through Week 24. | From Baseline to Week 24 |
| Phase 2: Proportion of participants with Protocol-Defined Pericarditis Recurrence by Week 24. | From Baseline to Week 24 |
| Phase 2: Change from Baseline in CRP through Week 24. | From Baseline up to Week 24 |
| Phase 2: Change from Baseline in pericarditis pain NRS score through Week 24. | From Baseline up to Week 24 |
| Phase 3: Change from RI Baseline in SF-36v2® Mental Component Summary score through the end of the RI Period | From Baseline up to the end of the RI Period |
| Phase 3: Time to Treatment Response by the end of the RI Period | From Baseline up to end of the RI Period |
| Phase 3: Time to KPL-387 monotherapy by the end of the RI Period | From Baseline up to end of the RI Period |
| Phase 3: Time to Pain Response by end of the RI Period | From Baseline up to end of the RI Period |
| Phase 3: Time to CRP normalization by the end of the RI Period | From Baseline up to end of the RI Period |
| Phase 3: Change from RI Baseline in SF-36v2® Physical Component Summary score through the end of the RI Period. | From Baseline up to end of the RI Period |
| Phase 3: Time to resolution of pericarditis manifestations (i.e., ECHO abnormalities, ECG abnormalities, and pericardial rub), when present at RI Baseline, by the end of the RI period. | From Baseline up to end of the RI Period |
| Phase 3: Change from RI Baseline in pericarditis pain NRS score through the end of the RI Period. | From Baseline up to end of the RI Period |
| Phase 3: Change from RI Baseline in CRP through the end of the RI Period. | From Baseline up to end of the RI Period |
| Phase 3: Proportion of participants who maintained Clinical Response at RW Week 16. | From Baseline up to RW Week 16 |
| Phase 3: Percentage of days with no or minimal pericarditis pain through RW Week 16. | From Baseline up to RW Week 16 |
| Phase 3: Change from RW Baseline in SF-36v2® Physical Component Summary score at RW Week 16. | From Baseline up to RW Week 16 |
| Phase 3: Change from RW Baseline in pain NRS score during the RW Period. | From Baseline through the end of the RW Period |
| Phase 3: Change from RW Baseline in CRP during the RW Period | From Baseline through the end of the RW Period |
| Long-Term Extension: Proportion of participants who maintained Clinical Response through the end of the LTE Period. | Up to 24 months |
| Long-Term Extension: Percentage of days with no or minimal pericarditis pain through the end of the LTE Period. | Up to 24 months |
| Long-Term Extension: Change from LTE Baseline in SF-36v2® Physical Component Summary score through the end of the LTE Period. | Up to 24 months |
| Long-Term Extension: Change from LTE baseline in pain NRS score through the end of the LTE Period. | Up to 24 months |
| Long-Term Extension: Change from LTE Baseline in SF-36v2® Mental Component Summary score through the end of the LTE Period. | Up to 24 months |
| Phase 2: Time to CRP Normalization (CRP ≤ 0.5 mg/dL) by Week 24 | From Baseline up to Week 24 |
| Phase 2: Time to Pain Response by Week 24 | From Baseline up to Week 24 |
Countries
Canada, France, Germany, Greece, Italy, Poland, Serbia, Spain, United Kingdom, United States
Contacts
CONTACTClinical Project Manager
Outcome results
None listed