Study to Evaluate the Efficacy and Safety of RPH-104 Treatment in Patients With Idiopathic Recurrent Pericarditis

Pericarditis Clinical Trial

Official title: A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of RPH-104 Treatment in Patients With Idiopathic Recurrent Pericarditis

Status Completed

Clinical Trial Summary

The goal of this study was to evaluate the Efficacy and Safety of RPH-104 Treatment in patients in comparison to placebo with Idiopathic Recurrent Pericarditis

Clinical Trial Description

The study included the following periods:

1. Screening period (up to 4 weeks); During the screening period, the patients' eligibility for the study was evaluated based on the inclusion/non-inclusion criteria. Those patients who were considered eligible for participation in the study were enrolled in the run-in treatment period.

2. Run-in treatment period (12 weeks, Days 0-84 - for the patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) and/or colchicine as the therapy for recurrent pericarditis (underlying disease), or 24 weeks, Days 0-168 - for the patients receiving glucocorticosteroids (GCSs) as monotherapy or in combination with NSAIDs and/or colchicine; Depending on the Protocol version, during the period, the patients received the product according to a schedule of 80 mg every two weeks, starting from Day 0 (Protocol version 2.0/3.0). The Protocol amendment (Version 4.0) was accompanied by the adjustment of the treatment regimen and, accordingly, the patients enrolled in the study according to Version 4.0 received the product starting with a loading dose of 160 mg (the first injection on Day 0) and then 80 mg on Day 7, Day 14, and then once every 2 weeks (1 time/2 weeks).

The treatment response during the run-in treatment period was defined as the resolution of the relapse observed at enrollment in the study, and the absence of new relapses of pericarditis in patients enrolled in the study with signs of pericarditis recurrence; absence of new relapses of pericarditis in patients enrolled without signs of relapse. In the absence of treatment response assessed on Day 14 of the study and then during the preparatory open-label period, the use of RPH-104 in patients was discontinued, and they were prescribed treatment with other drugs at the Investigator's choice.

After two weeks of open-label therapy (starting from Day 14 of the run-in treatment period), patients with a response to the study drug treatment began to discontinue the previous treatment of the underlying disease. Monotherapy with NSAIDs, colchicine, or their combination was discontinued simultaneously. The GCS dose was gradually tapered over 12 weeks with subsequent complete discontinuation (thus, these patients received RPH-104 in combination with GCS for 14 weeks and RPH-104 as monotherapy for the next 10 weeks).

The patients who demonstrated response to therapy with RPH-104 during the run-in treatment period, were transferred to the randomized withdrawal period.

3. Randomized withdrawal period (24 weeks: Day 0 since the randomization - Day 168 since the randomization) included treatment with RPH-104 or placebo depending on the randomization group (1:1 ratio) once in 2 weeks and the efficacy and safety monitoring procedures; Patients have been receiving therapy for a period of 24 weeks: the study drug group (to receive RPH-104 80 mg SC) or placebo group (to receive an equivalent volume of placebo subcutaneous (SC)).

In case of recurrence of pericarditis during the period of randomized withdrawal (regarded as a lack of response), the treatment group was unblinded. Patients in the placebo group were prescribed open-label therapy with RPH-104 as a single dose of 160 mg subcutaneously (first injection), followed by administration of 80 mg every 7 days, 14 days after the first injection. Also, at the Investigator's discretion, the use of NSAIDs and/or colchicine was allowed for relapse treatment in these patients. The response to therapy in such patients was assessed 3 days and 7 days after the first open-label injection of the study drug, according to the results of which, if the relapse was not resolved, the same treatment regimen was continued (including NSAIDs and/or colchicine). Evaluation of the drug efficacy in these patients was carried out 14 days after switching to active study drug treatment. In case of resolution of the developed relapse, the use of NSAIDs/colchicine was to be discontinued simultaneously, the use of the study drug was to be continued at a dose of 80 mg once every other week with an efficacy assessment every 4 weeks until the end of the randomized withdrawal period of the study.

Patients from the RPH-104 group (as well as patients from the placebo group who were switched to the study drug therapy due to a disease recurrence, those in whom the recurrence did not resolve within 14 days, or patients who developed a new recurrence after the resolution of the previous one) were switched to treatment with other drugs at the discretion of the Investigator; these patients had to come to a follow-up safety visit in 2 and 8 weeks after the administration of the last dose of the study drug.

Thus, after the end of randomized withdrawal period, the patients who responded to therapy with RPH-104 were asked to transfer to the open-label study to evaluate the long-term safety and efficacy of RPH-104. Non-responders, as well as patients who did not agree to participate in the open-label study of safety and efficacy, had to come to follow-up safety visits.

4. Safety follow-up period included monitoring of safety for 8 weeks after the last dosing of the study drug.

Thus, the maximum duration of treatment in this study was 36 weeks (for patients who were receiving NSAIDs and/or colchicine at the study enrollment) and 48 weeks (as a monotherapy or in combination with NSAIDs and/or colchicine).

The total maximal duration of the study was planned to be approximately 60 weeks.

A total of 20 patients with idiopathic recurrent pericarditis were planned to be randomized into the study. Taking into account potential dropouts during the screening and the run-in treatment period, the number of screened patients (signing the Informed Consent Form) could be as large as 35. ;

Related Conditions & MeSH terms

• Pericarditis

• NCT number: NCT04692766
• Study type: Interventional
• Source: R-Pharm
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: February 12, 2020
• Completion date: March 22, 2022