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

NCT05092776 | Active Not Recruiting Phase 2

• 1 other identifier: CL04018065
• Study Type: interventional
• Target: 84
• Locations: 4 countries
• Sites: 14

Brief 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.

Conditions

Familial Mediterranean Fever; FMF

Keywords

RPH-104; colchicine inefficacy; colchicine intolerance; subcutaneous

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with complete response during 16 week therapy with RPH-104 vs. placebo in FMF subjects with colchicine inefficacy or intolerance.

  Complete response defined as resolution of "marker" attack by Visit 2 (Day 7) and lack of recurrent attacks during the treatment period up to Visit 10 (Day 112). Criteria of resolution of a "marker" FMF attack include simultaneous clinical and laboratory signs of the attack resolution: * Physician Global Assessment (PGA) score \< 2 (i.e. minimum or complete lack of clinical signs and symptoms) AND * C-reactive protein (CRP) level ≤ 10 mg/L OR CRP reduction by ≥ 70% compared to baseline defined at enrollment to treatment period (Visit 1). Criteria of a recurrent FMF attack development after resolution of "marker" attack include simultaneous development of clinical and laboratory signs of the attack: * PGA score ≥ 2 assuming mild, moderate or severe disease activity (i.e. clinical signs), AND * CRP level ≥ 30 mg/L (serological signs). PGA is a 5-point scale: from 0 = no disease-related clinical signs and symptoms to 4 = severe clinical signs and symptoms of the disease.

  Up to 16 weeks

Secondary Outcomes (11)

• Time to the development of a recurrent FMF attack in patients with resolved "marker" attacks

  from Day 7 to the development of a recurrent FMF attack, up to 16 weeks

• Proportion of subjects with Physician Global Assessment (PGA) score < 2 during the study

  Up to 16 weeks

• Proportion of subjects with partial response to treatment

  Up to 16 weeks

• Proportion of subjects with serological remission

  Up to 16 weeks

• Proportion of subjects with normalized Serum Amyloid A (SAA) level

  Up to 16 weeks

Study Arms (2)

RPH-104

EXPERIMENTAL

Test product group receiving RPH-104 subcutaneous (s.c.) injections:160 mg on Day 0, 80 mg on Day 7, Day 14 and every 2 weeks (q2w) thereafter. In case "marker" attack does not resolve at Visit 2 - the treatment group will be unblinded: patients will receive planned RPH-104 80 mg administration. In case of a new attack on further days of treatment period until Visit 10 inclusive - the treatment group will be unblinded: the dose of RPH-104 could be escalated to 160 mg q2w; The patients already receiving RPH-104 160 mg q2w will continue to receive RPH-104 at this dose. Further dose escalation is forbidden.

Biological: RPH-104

Placebo

PLACEBO COMPARATOR

Placebo group receiving the equivalent placebo dose also as s.c. injections on Day 0, Day 7, Day 14 and q2w thereafter. In case the "marker" attack does not resolve at Visit 2 - the treatment group will be unblinded: patients will be switched to active treatment with RPH-104 in SC injections at a dose of 160 mg followed by administration of 80 mg in 7 days at the Attack + 7 days Visit, and 80 mg at the next Visits. In a case of a new attack the patients switching from placebo and receiving RPH-104 at 80 mg dose could be escalated to RPH-104 160 mg q2w; Further dose escalation is forbidden.

Drug: Placebo

Interventions

RPH-104 BIOLOGICAL

solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL glass vial

RPH-104

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of voluntarily signed and dated ICF to participate in this study.
• Verified diagnosis of familial Mediterranean fever (FMF) based on Tel HaShomer diagnostic criteria (Pras M., 1998) or the criteria developed by the Eurofever /Pediatric Rheumatology International Trials Organization (PRINTO) expert group (2019);
• Presence of at least one mutation in Mediterranean fever gene (MEFV) exon 10 (results of the study performed earlier at any time may be provided or a respective test should be performed during the screening);
• Presence (at screening onset) of data on history of at least one (on average) disease attack per month throughout the last 3 months (Ozen et al., 2020);
• Presence of at least one of the below-mentioned (at screening onset) documented data confirming:
• resistance to colchicine at the maximum tolerable therapeutic dose (up to 3 mg/day) confirmed by at least one monthly attack (on average) despite the therapy specified within at least 3 last months. Colchicine administration will be continued at stable dose if it is not associated with unacceptable adverse reactions;
• intolerance of therapeutic or subtherapeutic doses of colchicine (unacceptable adverse reactions); Colchicine dose should be stable for at least 5 days before patient enrollment into the study (prior to screening onset).
• Ability and willingness of the subject, according to the reasonable Investigator's judgment, to attend the study site at all scheduled visits, undergo the study procedures and follow the Protocol requirements including subcutaneous (SC) injections by qualified site personnel;
• Consent of female subjects of childbearing potential defined as all females with physiological potential to conceive (except for those with absolute termination of menses to be determined retrospectively after 12 months of natural amenorrhea, i.e. amenorrhea with relevant clinical status, e.g. appropriate age) to use highly effective contraception throughout the study starting from the screening (signed ICF) and for at least 8 weeks after the study treatment completion (discontinuation); and negative pregnancy test (serum test for human chorionic gonadotropin (HCG)).
• or Consent of the sexually active men subjects to use highly effective contraception throughout the study starting from the screening (signed ICF) and for at least 8 weeks after the study treatment completion (discontinuation).
• A highly effective method of contraception is defined as follows:
• complete abstinence: if it corresponds to the preferred and conventional lifestyle of the female subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation method) and interrupted coitus are not considered acceptable contraceptive methods;
• female sterilization: surgical bilateral ovariectomy (with/without hysterectomy) or tubal ligation at least 6 weeks prior to the study treatment initiation. In case of ovariectomy only the female reproductive status should be verified by further hormonal test;
• male sterilization (with documented absence of sperm in ejaculate post vasectomy) at least 6 months for screening. Vasectomized male partner should be the only partner of the participating female subject;
• combination of two of the following methods (a+b or a+c or b+c):

You may not qualify if:

• Hypersensitivity to the study product (RPH-104) and/or its components/excipients.
• Administration of live (attenuated) vaccines less than 3 months prior to Day 0 (treatment initiation) and/or necessity to use such vaccine within 3 months after the study product RPH-104 treatment completion (discontinuation). Live attenuated vaccines include viral vaccines against: measles, rubella, parotitis, varicella, rotavirus, influenza (as nasal spray), yellow fever, poliomyelitis (oral polio-vaccine); tuberculosis vaccine (BCG), typhoid (oral typhoid fever vaccine) and camp fever (epidemic typhoid vaccine). Immunocompetent family members should refuse to use oral polio-vaccine throughout the subject's participation in the study.
• Conditions or signs which, according to the investigator, evidence impaired (reduced) immune response and/or significantly increase the risk of immunomodulating therapy including (but not limited to):
• active bacterial, fungal, viral or protozoal infection at screening onset;
• opportunistic infections and/or Kaposi's sarcoma at the screening period onset;
• chronic bacterial, fungal or viral infection requiring systemic therapy with parenteral products at the main screening period onset;
• human immunodeficiency (HIV), hepatitis B (HBV) or C (HCV) viral infections;
• Active tuberculosis (TB) in the history or risk factors or signs evidencing active or latent infection with M. Tuberculosis including (not limited to) the following:
• living in specific conditions increasing the risk of contact with tuberculosis such as detention facilities, in crowded areas of person of no fixed abode, etc. within the last year before the main treatment period;
• working in a medical institution with unprotected contact with subjects under high risk of tuberculosis or subjects with tuberculosis within the last year until the main therapy period;
• close contact, i.e. confinement to a place (home or another confined area) for a long period of time (several days or weeks, not minutes or hours) with a subject with active pulmonary tuberculosis within the last year until the main therapy period;
• results of examinations indicating active or latent infection with M. Tuberculosis: positive QuantiFERON-TB / T-Spot TB test at screening; chest X-ray/chest CT findings confirming pulmonary tuberculosis during screening.
• Any other relevant concomitant diseases (cardiovascular, nervous, endocrine, urinary, gastrointestinal, hepatic disorders, coagulation disorders, other autoimmune diseases, etc.) or conditions which, according to the investigator's judgment, may affect the subject's participation or well-being in the study and/or distort assessment of the study results.
• History of organ transplantation or necessity in transplantation at the screening onset.
• Any malignancies during the screening period or for 5 years before screening except for non-metastatic basal cell and squamous cell skin cancer after total resection or in situ carcinoma of any type after total resection.

Sponsors & Collaborators

• R-Pharm International, LLC: lead
• Data Management 365: collaborator
• Atlant Clinical LLC: collaborator
• R-Pharm JSC: collaborator
• Unimed Laboratories: collaborator
• Exacte Labs LLC: collaborator
• Key Stat LLC: collaborator
• TRPharm İlaç Sanayi Ticaret Anonim Şirketi and ASCOT SCIENCE Education and Consulting Ltd.: collaborator
• Ascot Eğitim ve Danışmanlık LTD. ŞTİ.: collaborator

Study Sites (14)

Center of Medical Genetics and Primary Health Care

Yerevan, 0001, Armenia

Location

Mikaelyan Institute Of Surgery CJSC

Yerevan, 0052, Armenia

Location

Inova LLC

Tbilisi, 0179, Georgia

Location

The First Medical Center Ltd.

Tbilisi, 0180, Georgia

Location

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Moscow, 119021, Russia

Location

Multidisciplinary Scientific and Clinical Center named after S.P. Botkin

Moscow, 125284, Russia

Location

Medical Technologies Ltd

Saint Petersburg, 191025, Russia

Location

Saint-Petersburg Pasteur Institute

Saint Petersburg, 197101, Russia

Location

Terafarm, Llc

Stavropol, 355000, Russia

Location

Hacettepe University Faculty of Medicine

Ankara, 06230, Turkey (Türkiye)

Location

Gazi University Faculty of Medicine

Ankara, 06560, Turkey (Türkiye)

Location

Akdeniz University Faculty of Medicine

Antalya, 07070, Turkey (Türkiye)

Location

Istanbul University Istanbul Faculty of Medicine

Istanbul, 34093, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Faculty of Medicine

Istanbul, 34098, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Familial Mediterranean Fever

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2021
• First Posted: October 26, 2021
• Study Start: April 29, 2021
• Primary Completion: January 1, 2025
• Study Completion: October 30, 2025
• Last Updated: December 6, 2024

Record last verified: 2024-12

Locations

AR (2); GE (2); RU (5); TU (5)