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

Familial Mediterranean Fever Clinical Trial

Official title: 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 Recruiting

Clinical Trial Summary

The primary purpose of this study is to assess the efficacy and safety profiles of investigational product RPH-104 (R-Pharm Overseas, Inc., USA) for treatment of Familial Mediterranean Fever (FMF) in adult patients resistant/intolerant to colchicine (crFMF). Pharmacokinetic and pharmacodynamic parameters of RPH-104 single or multiple doses in this patient population will be assessed as well.

Clinical Trial Description

The study is supposed to enroll (randomize) 60 subjects with familial Mediterranean fever (FMF) with colchicine inefficacy or intolerance. Given potential withdrawal at the screening, the number of screened subjects (signed informed consent) will be approximately 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, 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 period 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.

3. Follow-up period (8 weeks).

On the first follow-up visit the subjects with therapeutic response to RPH-104 will be invited to proceed in an open-label long-term safety study of RPH-104. 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.

Overall expected study period is approximately 37 months. ;

Related Conditions & MeSH terms

• Brucellosis
• Familial Mediterranean Fever
• Fever
• FMF
• Hereditary Autoinflammatory Diseases

• NCT number: NCT05092776
• Study type: Interventional
• Source: R-Pharm
• Status: Recruiting
• Phase: Phase 2
• Start date: April 29, 2021
• Completion date: October 2024