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

Inclusion Criteria:

1. The patient with Familial Mediterranean Fever (FMF) with resistance to orintolerance of colchicine, who completed the core study, during which he/shereceived at least one dose of RPH-104.

2. Voluntarily signed and dated Patient Informed Consent Form (ICF) for participationin this study.

3. The patient's ability and desire, according to the Investigator's discretion, tofollow the schedule of visits, follow the study procedures and follow the Protocolrequirements, including the following:

• to visit the study site every 2 weeks for RPH-104 administration by qualifiedstudy site personnel

or

• to learn the subcutaneous (SC) injection technique and self-administer RPH-104 at his/her accommodation as per the study Protocol

or

• to agree with the qualified medical personnel visits to his/her accommodation for RPH-104 administration.

Exclusion Criteria:

1. Any medically significant event that was observed in a patient during his/herparticipation in the core study, as well as any other medical conditions (includingpsychiatric disorders) or laboratory abnormalities, which may increase the potentialrisk associated with participation in the study and treatment with RPH-104, or mayaffect the interpretation of the study results, and which, according to theInvestigator's opinion, may lead to the patient's non-compliance with the studyinclusion criteria.

2. Pregnant and/or lactating women or women planning pregnancy during the study orwithin 2 months after the last RPH-104 dose.

3. Women of childbearing potential, i.e. all females with physiological ability toconceive except for those with final cessation of menses, which should be determinedretrospectively after 12 months of natural amenorrhea, i.e. amenorrhea with anappropriate clinical status, for example, at respective age, who do not agree to usehighly effective contraceptives throughout the study, starting from the moment ofsigning the ICF and for at least 8 weeks after the last RPH-104 dose or Men who aresexually active and do not agree to use highly effective contraceptives throughoutthe study, starting from the moment of signing the ICF and for at least 8 weeksafter the last RPH-104 dose. Highly effective contraception methods include:

• complete abstinence: if it corresponds to the preferred and conventionallifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation,symptothermal, postovulation method) and interrupted coitus are not consideredacceptable contraceptive methods;

• female sterilization: surgical bilateral ovariectomy (with/withouthysterectomy) or tubal ligation at least 6 weeks before the start of the corestudy. In a case of ovariectomy only, the female reproductive status should beverified by further hormonal test;

• male sterilization (with documented absence of sperm in ejaculate postvasectomy) at least 6 months before the start of the core study. Vasectomizedmale partner should be the only partner of the participating female subject;

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

1. use of oral, injectable or implanted hormonal contraceptives; in a case oforal contraceptives, the woman should constantly use the same product aswas used during the core study;

2. installation of an intrauterine device or contraceptive system;

3. use of barrier contraceptives: condom or occlusive cap (diaphragm orcervical cap/contraceptive vaginal ring) with spermicidalfoam/gel/film/cream/vaginal suppository

4. The need for a therapy with any of the following products from the moment of signingthe ICF till the study treatment period completion:

• systemic glucocorticoids at a dose exceeding 0,2 mg/kg/day of prednisolone (or 0,16 mg/kg/day of methylprednisolone, or an equivalent dose of anotherglucocorticoid) orally;

• rilonacept, tocilizumab, rituximab, canakinumab, tumor necrosis factor alpha (TNF-a) inhibitors (TNFi) and other biological products (except for RPH-104);

• immunosuppressants (cyclosporine, methotrexate, leflunomide, thalidomide,azathioprine, 6-mercaptopurine, cyclophosphamide, etc.);

• methylprednisolone (or an equivalent) at a dose of more than 40 mg/dayparenterally;

• intramuscular, intra-articular or peri-articular administration ofglucocorticoids;

• anakinra;

• tofacitinib, baricitinib;

• any experimental drugs (except for RPH-104)

5. The need to use a live (attenuated) vaccine during the study or within 3 monthsafter the last RPH-104 dose. Live attenuated vaccines include vaccines againstviruses: 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). Immunocompetentfamily members of the patient should not be vaccinated with the oral polio vaccineduring the patient's participation in the study

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

7. Participation in other experimental studies (except for the core study).