Safety and Efficacy of RPH-104 Used to Prevent Recurrent Fever Attacks in Adult Patients With Colchicine Resistant or Colchicine Intolerant Familial Mediterranean Fever

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Brief Title

Safety and Efficacy of RPH-104 Used to Prevent Recurrent Fever Attacks in Adult Patients With Colchicine Resistant or Colchicine Intolerant Familial Mediterranean Fever

Official Title

An International Multicenter Open-label Clinical Study of the Safety and Efficacy of RPH-104 for Prevention of Recurring Attacks in Adult Subjects With Familial Mediterranean Fever With Resistance to or Intolerance of Colchicine

Brief Summary

      The primary purpose of this study is to assess the safety of the long-term treatment with
      RPH-104 at doses 80 mg or 160 mg once every 2 weeks in a population of patients with
      colchicine resistant or colchicine intolerant familial Mediterranean fever (FMF) who
      completed the core study, during which they received at least one dose of RPH-104. Long-term
      efficacy of RPH-104, the immunogenicity of the RPH-104, the pharmacokinetics of the RPH-104
      and quality of life change in the population of patients receiving long-term treatment with
      RPH-104 will be assessed as well.
    

Detailed Description

      This long-term open-label study is an extension of the core double blind, randomized,
      placebo-controlled study, CL04018065. It is planned that this study will include no more than
      60 patients who completed the core study, where they received blinded therapy.

      This study will have the following periods:

        1. Screening period - within one day, Day 0, which is also the day of Visit 11 of the main
           study. This period envisages unblinding of the treatment groups determined in the main
           study (for not-unblinded patients) and determination of the eligibility for this study.
           Patients who do not meet the inclusion/exclusion criteria will not receive treatment
           with the study drug, such patients should attend a safety follow-up visit 6 weeks after
           the screening period (i.e. 8 weeks after the last injection of the study drug or placebo
           during the core study) with all procedures performed in accordance with the last planned
           visit of the safety follow-up (Visit 17), after which their participation in the study
           will be considered completed.

        2. Treatment period - all patients included in this period will receive open-label
           treatment with RPH-104 for 54 weeks. The possible drug dose will be:

             -  80 mg once every 2 weeks subcutaneously;

             -  160 mg once every 2 weeks subcutaneously.

           An injection of the study drug to patients is performed by qualified medical personnel
           every 2 weeks when the patient visits the study site; it is also possible for the
           patients to self-administer the drug at home (for which patients will be appropriately
           trained and provided with the necessary quantity of the drug, materials for the
           injection (including special containers for their disposal) and proper drug
           transportation).

           Safety and efficacy assessments are performed at Visit 1, Visit 2 (after 2 weeks) and
           then every 4 weeks according to the visits schedule. Safety and efficacy assessments are
           performed at Visit 1, Visit 2 (after 2 weeks) and then every 4 weeks according to the
           visits schedule.If FMF attack is confirmed in a patient, then patient's therapy can be
           adjusted based on the informed decision of an investigator:

             -  for patients who receive RPH-104 at a dose of 80 mg q2w, a dose can be increased to
                160 mg q2w;

             -  for patients who already receive the maximum dose of RPH-104 that is 160 mg q2w,
                the dose will be not increased; these patients will be able to continue therapy
                with the study drug at a dose of 160 mg at the justified investigator's discretion.

           Reduction of the study drug dose is not planned in this study.

        3. Safety follow-up period - 8 weeks. After patients receive the last dose of the study
           drug at Week 54 of the study, the treatment period will be considered completed and an 8
           weeks period of safety follow-up will start. During this period patients will have to
           visit the study site twice at Week 4 and Week 8 after the last dose of the study drug
           for safety assessments. Patients who have discontinued open-label therapy with the study
           drug early for any reason, should perform two safety follow-up visits at Week 4 and Week
           8 after the last dose of the study drug.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term

Secondary Outcome

 Physician global assessment of disease activity scale (PGA)

Condition

Familial Mediterranean Fever

Intervention

RPH-104

Study Arms / Comparison Groups

 RPH-104 80 mg q2w (160 mg q2w) depending on the dose in the core CL04018065 study
Description:  RPH-104 80 mg once every 2 weeks subcutaneously or RPH-104 160 mg once every 2 weeks subcutaneously (In case of FMF attack development, patients who receive 80 mg of the drug may be switched to the increased maximum drug dose 160 mg based at the discretion of the investigator. A dose of 160 mg should be administered by two subcutaneous injections in two different quadrants.)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

60

Start Date

October 5, 2021

Completion Date

January 11, 2023

Primary Completion Date

January 11, 2023

Eligibility Criteria

        Inclusion Criteria:

          1. The patient who completed the last visit of the treatment period in the core study,
             according to the protocol, during which he/she received at least one dose of RPH-104.

          2. Voluntarily signed and dated Patient Informed Consent Form for participation in this
             study.

          3. The patient's ability and desire, according to the investigator, to follow the
             schedule of visits, follow the study procedures and follow the protocol requirements,
             i.e they agree to:

               -  come to the study site every 2 weeks for the investigational product
                  administration by qualified site staff. OR

               -  learn the subcutaneous injection technique and self-administer the
                  investigational product at home as per protocol of this study.

        Exclusion Criteria:

          1. Any medically important event that was observed in a patient during his/her
             participation in the core study, and, in the opinion of the investigator, is a reason
             for not including this patient in the present study, and any other medical (including
             psychiatric) conditions or laboratory abnormalities, which may increase the potential
             risk associated with participation in the study and receiving the investigational
             product, or may affect the interpretation of the results of the study, and which, in
             the Investigator's reasonable opinion, result in the patient's non-compliance with the
             inclusion criteria

          2. Pregnant and/or lactating women or women planning pregnancy during the study or within
             2 months after the last dose of the study drug.

          3. Women of childbearing potential, i.e. all women with the physiological ability to
             become pregnant (except for women with a final cessation of menstruation, which should
             be determined retrospectively after 12 months of natural amenorrhea, i.e. amenorrhea
             with an appropriate clinical status, for example, an appropriate age), who DO NOT
             agree to use highly effective contraception for of the entire study period, starting
             from the beginning of the screening phase (signing informed consent) and for a minimum
             of 8 weeks after the last dose of the study drug. OR

             Men who are sexually active and do NOT agree to use highly effective contraceptives
             throughout the study, starting from the beginning of the screening phase and for at
             least 8 weeks after the last dose of the study drug.

             Highly effective contraception methods include:

               -  sterilization in women: surgical bilateral removal of the ovaries (with or
                  without removal of the uterus) or ligation of the fallopian tubes at least 6
                  weeks before the start of the study therapy. In the case of removal of only the
                  ovaries, the reproductive status of a woman should be confirmed by a subsequent
                  assessment of hormone level;

               -  sterilization in men, at least 6 months before the start of the study therapy
                  with proper documentation of the absence of sperm in the ejaculate after
                  vasectomy. For the women participating in the study, the sexual partner after a
                  vasectomy should be the only partner;

               -  using a combination of any two of the following methods (a+b or a+c or b+c):

                    1. the use of oral, injectable or implanted hormonal contraceptives; in the
                       case of the use of oral contraceptives, women should constantly use the same
                       drug for at least 3 months before the start of the study therapy;

                    2. the installation of an intrauterine device or contraceptive system;

                    3. barrier methods of contraception: condom or occlusive cap (diaphragm or
                       cervical cap/contraceptive vaginal ring) with spermicidal
                       foam/gel/film/cream/vaginal suppository.

          4. The need for systemic glucocorticoid therapy at doses > 0.2 mg/kg/day of prednisolone
             (0.16 mg/kg/day of methylprednisolone or an equivalent dose of another glucocorticoid)
             orally from the moment of signing the Informed Consent Form to the end of the period
             of therapy with the study drug.

          5. The need to use a live (attenuated) vaccine during the study or within 3 months after
             the last dose of the study drug. Live attenuated vaccines include vaccines against
             viruses: measles, rubella, mumps, chickenpox, rotavirus, flu (as a nasal spray),
             yellow fever, polio (oral polio vaccine); vaccines against tuberculosis (BCG), typhoid
             fever (oral typhoid vaccine) and typhus (typhus vaccine). Immunocompetent family
             members of the patient should not be vaccinated with the oral polio vaccine during the
             patient's participation in the study.

          6. Positive results of tuberculosis screening performed at Visit 10 of the core study
             (QuantiFERON-TB/T-SPOT.TB test, chest x-ray).
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Mikhail Samsonov, , 

Location Countries

Armenia

Location Countries

Armenia

Administrative Informations


NCT ID

NCT05190991

Organization ID

CL04018071


Responsible Party

Sponsor

Study Sponsor

R-Pharm International, LLC

Collaborators

 Atlant Clinical LLC

Study Sponsor

Mikhail Samsonov, Study Director, R-Pharm


Verification Date

January 2022