UMIN-CTR Clinical Trial

Basic information
Public title	Randomized, double-blind, parallel group comparison trial of Tocilizumab for colchicine-resistant familial Mediterranean fever
Acronym	Clinical trial of Tocilizumab for colchicine-resistant familial Mediterranean fever
Scientific Title	Randomized, double-blind, parallel group comparison trial of Tocilizumab for colchicine-resistant familial Mediterranean fever
Scientific Title:Acronym	Clinical trial of Tocilizumab for colchicine-resistant familial Mediterranean fever
Region	Japan

Condition
Condition	familial Mediterranean fever
Classification by specialty	Clinical immunology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	To assess the efficacy, safety and pharmacokinetics of Tocilizumab by placebo-controlled trial
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Number of fever attacks (up to 4 times) at 24 weeks
Key secondary outcomes	[Efficacy (at 24 weeks)] (1) Number of occurrences of accompanying symptoms during attacks (2) Time until fever attack occurs (3) Duration of fever attack (4) serum CRP, SAA (5) SF-36 Health Survey Questionnaire (6) General evaluation by doctor (100 mm VAS) (7) Body temperature (8) Percentage of achievement of FMF 50 at 12 weeks and 24 weeks [Safety] Adverse event [PK] Serum Tocilizumab level, CRP, ESR, sIL-6 receptor

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Tocilizumab
Interventions/Control_2	Placebo
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	12 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	For patients who satisfy all the following conditions [Temporarily registered] Temporary registration is permitted when the target patient meets all the following criteria. (1) Patients diagnosed as familial Mediterranean fever (clinically typical) according to the following diagnostic criteria ("Regarding diagnostic criteria and severity classification related to designated intractable diseases" by the Ministry of Health, Labor and Welfare) (2) Patients with colchicine ineffective or colchicine inadequate (3) Patients who aged 12 to over 75 years old (regardless of gender) (4) Patients who got adequate explanation about the contents of explanatory documents and other matters concerning clinical trials, understand the contents thereof, and obtain written consent based on free will about participation in this trial [When randomized] When provisionally registered patient meets all the following criteria, it is randomly assignable. (1) Patients who had a fever attack (a fever that lasted more than 6 hours and had a fever over 38.0 during the observation period (2) Patients who could exclude diseases other than familial Mediterranean fever, which cause fever, such as infectious diseases (3) Patients whose fever attacks had disappeared during the observation period [Rescue transition] It allows for transition to rescue when the target patient meets all the following criteria. (1) Patients who received one or more investigational drugs in a double-blind period (2) Patients who have experienced more than four fever attacks since the start of the study drug administration. (3) Patients whose fever attacks of (2) had disappeared (4) Patients judged by investigators or clinical trial doctors to be appropriate from a safety point of view (5) Patients who got consent from subjects and substitutes (subjects under 20 years of age)
Key exclusion criteria	Patients applicable to even one of the following are excluded from the subject (1) Women who are breast-feeding, pregnant, or may become pregnant (2) Patients who have obvious infection within 4 weeks before the study and judged inappropriate by investigator or clinical trial doctor (3) Patients with a history of hypersensitivity to the components of tocilizumab (4) Patients who are recently being treated with biologics. (5) Patients with past history of tocilizumab (6) Patients who are routinely using corticosteroids (excluding topical therapy such as external preparations) due to diseases other than familial Mediterranean fever and whose investigator or clinical trial doctor judged inappropriate (7) Investigational drugs Patients falling under any of the following criteria for examination within one week prior to initial administration 1) Leukocyte count less than 3500 / microL 2) neutrophil count less than 1000 / microL 3) Lymphocyte count less than 500 / microL 4) Number of platelets less than 100000 / microL (8) Patients with active tuberculosis (9) Patients with a history of intestinal perforation (10) Patients who have interstitial pneumonia and who are judged inappropriate by investigators or clinical trial doctors (11) Patient diagnosed as having a malignant tumor within 5 years before the study. (12) Patients with active type B or C hepatitis or patients with a history of hepatitis B (13) Patients who have complicated serious diseases and who are judged inappropriate by investigators or clinical trial doctors as clinical trials (14) Patients inoculated with a live vaccine within 6 weeks before the study (15) Patients who are using other investigational drugs within 6 months before the initial investigational drug (16)Patients judged inappropriate by investigators or clinical trial doctors
Target sample size	24

Research contact person
Name of lead principal investigator	1st name Kawakami Middle name Last name Atsushi
Organization	Nagasaki University Graduate School of Biomedical Sciences
Division name	Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences
Zip code	8528501
Address	Sakamoto 1-7-1, Nagasaki
TEL	095-819-7260
Email	atsushik@nagasaki-u.ac.jp

Public contact
Name of contact person	1st name Kawakami Middle name Last name Atsushi
Organization	Nagasaki University Graduate School of Biomedical Sciences
Division name	Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences
Zip code	8528501
Address	Sakamoto 1-7-1, Nagasaki
TEL	095-819-7260
Homepage URL
Email	atsushik@nagasaki-u.ac.jp

Sponsor
Institute	Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Institutional Review Board, Nagasaki University Hospital
Address	1-7-1 Sakamoto, Nagasaki 852-8501
Tel	095-819-7256
Email	2745@ml.nagasaki-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	長崎大学病院（長崎県）、千葉大学医学部附属病院（千葉県）、福島県立医科大学附属病院（福島県）、九州大学病院（福岡県）、京都大学医学部附属病院（京都府）、金沢大学附属病院（金沢県）、信州大学医学部附属病院（長野県）、横浜市立大学附属病院（神奈川県）、国立大学法人北海道大学病院（北海道）

Other administrative information
Date of disclosure of the study information	2017 Year 07 Month 07 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	23
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2017 Year 09 Month 12 Day
Date of IRB	2018 Year 09 Month 28 Day
Anticipated trial start date	2018 Year 03 Month 01 Day
Last follow-up date	2019 Year 12 Month 10 Day
Date of closure to data entry	2019 Year 12 Month 27 Day
Date trial data considered complete	2020 Year 02 Month 12 Day
Date analysis concluded	2020 Year 03 Month 27 Day

Other
Other related information

Management information
Registered date	2017 Year 06 Month 30 Day
Last modified on	2021 Year 12 Month 16 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032030