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