NCT05092776

Efficacy and Safety of RPH-104 for Resolution and Prevention of Recurring Attacks in Adult Subjects With Familial Mediterranean Fever With Resistance to or Intolerance of Colchicine

International, Multicenter, Double Blind, Placebo-controlled, Randomized Clinical Study of Efficacy and Safety of RPH-104 for Resolution and Prevention of Recurring Attacks in Adult Subjects With Familial Mediterranean Fever With Resistance to or Intolerance of Colchicine

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 84 (estimated)
• Sponsor: R-Pharm International, LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Study purpose is an evaluation of efficacy and safety of RPH-104 in the population of subjects with Familial Mediterranean Fever (FMF) with colchicine resistance or intolerance(i.e. colchicine resistant (crFMF).. Primary objective is to determine proportion of subjects with complete response to treatment with RPH-104 compared to placebo among FMF subjects with colchicine resistance or intolerance.

Detailed description

The study is supposed to enroll (randomize) (n= not less than 28, not less than 14 per group), so that not less than 24 to complete study in full (including all the treatment period visits and follow-up period visits - Visit 11 for patients who agreed to participate in the Open-label extension (OLE) study; Visit 11 and Visit 12 for those who do not wish to participate in the OLE study; given potential withdrawal at screening the number of screened subjects (signed Informed Consent Form (ICF) is planned to be up to 84. The study will consists of three following periods: 1. Screening period (up to 12 weeks); Throughout the screening the subjects will be monitored to identify "marker" attacks and verify the subject eligibility. The subjects having an attack during screening period and meeting inclusion/exclusion criteria will be enrolled into treatment period. 2. Double-blind randomized placebo-controlled treatment period (16 weeks); The subjects enrolled will be randomized to one of the treatment groups in 1:1 ratio: * RPH-104 group to receive subcutaneous (SC) injections according to the following regimen: 160 mg on Day 0, 80 mg on Day 7, Day 14 and once every 2 weeks (q2w) thereafter; * placebo group to receive matching SC injections on Day 0, Day 7, Day 14 and q2w thereafter. Efficacy assessment will be performed at Visit 2 and Visit 3, and subsequently every 2 weeks up to Visit 10 inclusive; safety assessment will be performed throughout the study (Visit 1 - Visit 12). In a case of adverse event (AE) development (or other safety reasons), additional unscheduled safety visits could be performed throughout the study. Starting from Visit 2, additional unscheduled visits due to suspected development of FMF attack could be performed. In a case of a recurrent attack, the patient should come to the study site within 2 days from the attack onset for the attack registration. The treatment response (i.e. the resolution of FMF "marker" attack/absence of recurrent attacks) will be assessed throughout the treatment period with the investigational products administered both blind and open-label. Responders will continue the study treatment with the assigned investigational products (RPH-104 or placebo as a single SC 2 mL injection q2w, based on the randomization group) in a blinded manner. In non-responders, the following treatment modifications are possible: * In a case the "marker" attack has not resolved by Visit 2 - the treatment group will be unblinded: * patients from placebo group will be switched to active treatment with RPH-104 in SC injections at a dose of 160 mg (single dose, first injection) followed by administration of 80 mg in 7 days at the Attack + 7 days Visit (with procedures corresponding to Visit 2), and 80 mg at the next scheduled Visit performed 1 week later than initially scheduled (with procedures corresponding to this Visit) after the Attack + 7 days Visit. * patients from RPH-104 group will receive planned RPH-104 80 mg administration. * In a case of recurrent FMF attack confirmation at a scheduled visit - the treatment group will be unblinded (if still blinded): * patients from placebo group will be switched to active treatment with RPH-104 in SC injections at a dose of 160 mg (single dose, first injection) followed by administration of 80 mg in 7 days at the Attack + 7 days Visit (with procedures corresponding to Visit 2), and then at the next scheduled Visit (with procedures corresponding to the further study schedule) and all the next scheduled visits every 2 weeks thereafter; * patients from RPH-104 group or patients who were switched from placebo group and receiving RPH-104 80 mg will receive RPH-104 160 mg administration at the visit and thereafter 160 mg q2w; * patients already receiving RPH-104 160 mg q2w in unblinded manner can continue treatment or can discontinue treatment at the discretion of Investigator, based on the risk/benefit assessment of the further RPH-104 treatment. * In a case of recurrent FMF attack confirmation at an unscheduled visit - the treatment group will be unblinded (if still blinded): * if a recurrent FMF attack is recorded and the subject visits the study site within 3 days before the next scheduled visit (starting from Visit 3), the subject will undergo all the next scheduled visit procedures including the unblinded RPH-104 administration and blood sampling provided for at this scheduled visit. The treatment rules for a scheduled visit described above are applicable in this case; * in a case of a recurrent attack and subject's arrival to the site more than 3 days before the next scheduled visit but not less than 7 days after the previous scheduled visit (starting from Visit 2), the unscheduled visit will be performed on the day of arrival to the study site (and the administration will be shifted from the planned next scheduled visit). The treatment rules for a scheduled visit described above are applicable in this case. Further the subject will not attend the next scheduled visit and all the visit procedures per Protocol should be performed as an unscheduled visit. Afterwards, the initially planned visits schedule for a patient will be kept; * in a case of unscheduled visit within 7 days after administration of the scheduled blinded RPH-104 80 mg dose or placebo all procedures planned for unscheduled visit to be performed. If at such unscheduled visit development of a recurrent attack is confirmed the subject will be unblinded: * patients from placebo group will be switched to active treatment with RPH-104 in SC injections at the unscheduled visit at a dose of 160 mg (single dose, first injection) followed by administration of 80 mg in 7 days at the Attack + 7 days Visit (with procedures corresponding to Visit 2), and 80 mg at the next scheduled Visit performed 1 week later (with procedures corresponding to this Visit) after the Attack + 7 days Visit; * patients from RPH-104 group or patients who were switched from placebo group and receiving RPH-104 80 mg q2w will receive RPH-104 80 mg administration at the visit and thereafter 160 mg q2w starting from the next scheduled visit; * patients already receiving RPH-104 160 mg q2w will not receive RPH-104 at this unscheduled visit and can continue treatment or can discontinue treatment at the discretion of Investigator, based on the risk/benefit assessment of the further RPH-104 treatment. For patients receiving RPH-104 at a dose of 160 mg q2w no further dose escalation is carried out. In a case of consequent recurrent attacks this patient may continue treatment with RPH-104 at a maximum dose of 160 mg q2w according to the Investigator's reasonable decision until the end of the study treatment period. No dose reduction of the investigational products could be made throughout the study. Maximum treatment duration is 16 weeks. Subjects receiving both blinded and unblinded therapy will undergo regular evaluation of efficacy and safety; the visits will be performed every 2 weeks for this purpose. At the last visit of the treatment period (Visit 10) after completion of all visit procedures the patients will be invited to proceed in a long-term open-label extension (OLE) study to evaluate the safety and efficacy study of RPH-104 (CL04018071). 3. Follow-up period (8 weeks) that includes safety monitoring for 8 weeks after the last dosing with the investigational products. In case of lacking relevant clinical response and if the subjects do not wish to participate in the open-label study, they should complete all safety follow-up visits. Therefore, the total maximum duration of participation of one patient in the study will be 37 weeks, id est (i.e.) about 9 months (1 additional week could be added to the overall study duration in case of switching from the placebo to the RPH-104 treatment for a subject due to the disease attack).

Conditions

• Familial Mediterranean Fever
• FMF

Interventions

Type	Name	Description
BIOLOGICAL	RPH-104	solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL glass vial
DRUG	Placebo	Normal Saline (0.9% Sodium Chloride solution for subcutaneous Injection), 2 mL in the 4 mL-glass vial. The placebo will contain no active pharmaceutical ingredients.

Timeline

• Start date: 2021-04-29
• Primary completion: 2025-01-01
• Completion: 2025-10-30
• First posted: 2021-10-26
• Last updated: 2024-12-06

Locations

14 sites across 4 countries: Armenia, Georgia, Russia, Turkey (Türkiye)