Overview
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.
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:
- 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.
- 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.
Eligibility
Inclusion Criteria:
- 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.
- Voluntarily signed and dated Patient Informed Consent Form for participation in this study.
- 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:
- 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
- Pregnant and/or lactating women or women planning pregnancy during the study or within 2 months after the last dose of the study drug.
- 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):
- 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;
- the installation of an intrauterine device or contraceptive system;
- barrier methods of contraception: condom or occlusive cap (diaphragm or cervical cap/contraceptive vaginal ring) with spermicidal foam/gel/film/cream/vaginal suppository.
- 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.
- 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.
- Positive results of tuberculosis screening performed at Visit 10 of the core study (QuantiFERON-TB/T-SPOT.TB test, chest x-ray).