REgiStry Of the NAtural History of recurreNt periCarditis in pEdiatric and Adult Patients
Location: Alaska Heart & Vascular Institute, Barnes-Jewish Hospital/Washington University, Brigham and Women's Hospital, Carnegie Mellon University, Cincinnati Children's Hospital Medical Center, Cleveland Clinic, Houston Methodist Hospital, Johns Hopkins University, Legacy Hospital and Health Center DBA Legacy Research Institute, Mayo Clinic in Rochester, Midwest Cardiovascular Research Foundation, Minneapolis Heart Institute Foundation, NYU Langone Health, Northwell Health - Lenox Hill Hospital, Pima Heart and Vascular, Scripps Health, Seattle Children's Hospital, TKL Research Inc., University of California - San Diego, University of Nebraska Medical Center, University of Vermont Medical Center, Virginia Commonwealth University
Conditions: Alaska Heart & Vascular Institute, Barnes-Jewish Hospital/Washington University, Brigham and Women's Hospital, Carnegie Mellon University, Cincinnati Children's Hospital Medical Center, Cleveland Clinic, Houston Methodist Hospital, Johns Hopkins University, Legacy Hospital and Health Center DBA Legacy Research Institute, Mayo Clinic in Rochester, Midwest Cardiovascular Research Foundation, Minneapolis Heart Institute Foundation, NYU Langone Health, Northwell Health - Lenox Hill Hospital, Pima Heart and Vascular, Scripps Health, Seattle Children's Hospital, TKL Research Inc., University of California - San Diego, University of Nebraska Medical Center, University of Vermont Medical Center, Virginia Commonwealth University
La Jolla, California
Saint Louis, Missouri
Fair Lawn, New Jersey
New York, New York
JoAnn Clair, PhD
781 431 9100
Efficacy and Safety of RPH-104 Treatment in Patients With Recurrent Pericarditis
Status: Not yet recruiting
Location: Virginia Commonwealth University
Conditions: Virginia Commonwealth University
Antonio Abbate, MD
The primary purpose of this study is the evaluation of the efficacy and safety of RPH-104 treatment in patients with recurrent pericarditis.
Pharmacokinetic and pharmacodynamic parameters of RPH-104 multiple doses in this patient population will be assessed as well.
This is a phase 2/3 seamless design study with one interim efficacy analysis. At stage 1 (assuming possible 10% dropout rate in run-in period and screening), around 25 patients will be enrolled. At least 20 patients will be randomized to receive either RPH-104 treatment or placebo.
During the interim analysis, the enrollment won’t be paused. Based on interim analysis results the study could be continued or closed. In the case of study continuation, the final estimated sample size is at least 72 patients to be randomized in the withdrawal period (including 20 or more patients randomized in the Stage 1 of the study). Assuming possible 10% dropout in run-in period and 45% dropout in screening period, approximately enrollment of 80 subjects are planned and around 146 subjects will be screened in this study.
The study will consists of five following periods:
- Screening period (up to 4 weeks). The patients’ eligibility for the study will be evaluated based on the eligibility criteria.
- Run-in (RI) single-blind treatment period (16 weeks) will include single- blind treatment with RPH-104 at a dose 160 mg subcutaneous (SC) on Day 0, and 80 mg on Day 7, Day 14 and thereafter once in two weeks (Q2W) for all patients.
The RI period includes:
- 2-weeks Stabilization period, during which blinded RPH-104 is administered on top of standard of care (SOC) pericarditis therapy, and the ongoing pericarditis episode is treated.
- 10- week Weaning period, during which patients are gradually tapered and stopped background SOC pericarditis therapy, while treatment with blinded RPH-104 continues. corticosteroids (CS) and analgesics (opioid and non-opioid) dose will be tapered starting at RI week 2 and will be stopped by Week 12. NSAIDs and colchicine will be tapered starting at RI Week 6 and will be stopped by Week 12. Opioid analgesics can be continued after Week 12 at stable doses through the end of the OL period if cannot be discontinued without withdrawal symptoms.
- 4-week Monotherapy period: patients who stopped of background SOC pericarditis therapy will continue to receive blinded RPH-104.
Patients who discontinue SOC therapy and achieve clinical response at Week 16 are eligible for randomization in the randomized withdrawal (RW) period.
- Randomized withdrawal (RW) period (24 weeks) includes double-blind treatment with RPH-104 80 mg or placebo Q2W depending on the randomization group.
- Open-label treatment period (OL) (12 weeks). After completion of the RW period, all subjects that did not discontinue study drug will be transferred to Open-Label (OL) period and will receive open-label RPH-104 80 mg once in two weeks.
- Safety follow-up period includes monitoring of safety for 8 weeks after the last dosing of the study drug for patients who decided not to participate in open label extension long-term safety study (CL04018108).
The total maximal duration of the study for an individual subject will be approximately 64 weeks.
Impact of CardiolRxTM on Recurrent Pericarditis
Location: Cleveland Clinic, Mayo Clinic in Rochester, MedStar Heart and Vascular Institute, Minneapolis Heart Institute Foundation, Pima Heart and Vascular, University of Vermont Medical Center, Virginia Commonwealth University
Conditions: Cleveland Clinic, Mayo Clinic in Rochester, MedStar Heart and Vascular Institute, Minneapolis Heart Institute Foundation, Pima Heart and Vascular, University of Vermont Medical Center, Virginia Commonwealth University
Andrea B Parker, PhD
+1 289 910 0862
Andrew Hamer, MD
Multi-center, open label Pilot Study. Patients who present with recurrent pericarditis will be screened and informed consent obtained.
Baseline assessments include the following: Clinical assessment, including vital signs, highest NRS pain score within the past 7 days of Day 1, 12-lead ECG; C-SSRS as well as hematology and blood chemistry and a pregnancy test for women with child-bearing potential.
Concomitant medications are recorded and any (S)AEs after informed consent has been obtained.
Study treatment will be initiated in the evening of Day 1, after all baseline assessments are completed.
Oral administration is as follows:
- Initial starting dose (Day 1 p.m. dose to Day 3 a.m. dose):5 mg/kg of body weight CardiolRxTM
- Day 3 p.m. dose to Day 10 a.m. dose: 7.5 mg/kg of body weight CardiolRxTM b.i.d.
- Day 10 p.m. dose to end of treatment period: 10.0 mg/kg of body weight CardiolRxTM b.i.d.
If the next higher dose after each study drug increase is not tolerated, the dose will be reduced to the previous tolerated dose.
Unless contraindicated in the opinion of the investigator, after 8 weeks of treatment, patients will enter an 18-week extension period (EP), in which they continue study treatment while their concomitant medications will be weaned.
Follow-up Procedures Every visit (before the next dose increase) the patient will be re-evaluated. This includes ECG monitoring at approximately 5 hours post-morning dose (Tmax) to surveil for deleterious effects on ECG intervals (particularly the QTc interval) and rhythm.
Drug titration will be dependent on investigator or designate interrogation of the ECGs and the absence of new, clinically significant abnormalities on those ECGs.
Vital signs, concurrent medication and (S)AEs will be recorded at all visits. Blood chemistry including liver function tests, hematology as well as INR assessments will be carried out at selected visits.
Final efficacy assessments will take place after 26 weeks of study treatment and include a clinical assessment, vital signs, pain score NRS, a 12-lead ECG, the C-SSRS, as well as laboratory assessments.
For patients who do not enter the EP, Final assessments will be done after 8 weeks.