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UMIN ID:

Recruitment status Open public recruiting
Unique ID issued by UMIN UMIN000030584
Receipt No. R000034918
Scientific Title MIRACLE (Methotrexate inadequate response patient with Rheumatoid Arthritis treated by Adalimumab in combination with Low-dose Methotrexate) Study
Date of disclosure of the study information 2017/12/27
Last modified on 2019/06/30

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Basic information
Public title MIRACLE (Methotrexate inadequate response patient with Rheumatoid Arthritis treated by Adalimumab in combination with Low-dose Methotrexate) Study
Acronym MIRACLE Study
Scientific Title MIRACLE (Methotrexate inadequate response patient with Rheumatoid Arthritis treated by Adalimumab in combination with Low-dose Methotrexate) Study
Scientific Title:Acronym MIRACLE Study
Region
Japan Asia(except Japan)

Condition
Condition Rheumatoid Arthritis
Classification by specialty
Clinical immunology Orthopedics
Classification by malignancy Others
Genomic information NO

Objectives
Narrative objectives1 This study is intended to evaluate the optimal dosage of methotrexate (MTX) as an add-on therapy to adalimumab (ADA) in patients with rheumatoid arthritis (RA) who do not achieve remission by MTX monotherapy, and to measure erythrocyte MTX-polyglutamates (MTX-PG) concentration to evaluate its relation to the efficacy and safety of MTX therapy in RA patients.
Basic objectives2 Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes SDAI remission rate at Week 48
Key secondary outcomes

Base
Study type Interventional

Study design
Basic design Parallel
Randomization Randomized
Randomization unit Individual
Blinding Open -no one is blinded
Control Dose comparison
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment Central registration

Intervention
No. of arms 3
Purpose of intervention Treatment
Type of intervention
Medicine
Interventions/Control_1 Study treatment will start with MTX 6 to 8 mg/week, which will be promptly escalated to the maximum tolerable dose (MTD) <= 25 mg/week (<= 16 mg/week in Japan) in line with EULAR Recommendations 2016, and will be in principle maintained at the MTD from Week 12 onward. Also, the dosage of MTX will remain unchanged from Week 20 to 24 except for dose reduction/interruption due to an adverse drug reaction (ADR).
If the dosage of MTX is maintained >= 10 mg/week and remission (SDAI <= 3.3) is achieved at Week 24, the MTX therapy will be continued up to Week 48 (ARM-1).
Interventions/Control_2 Study treatment will start with MTX 6 to 8 mg/week, which will be promptly escalated to the maximum tolerable dose (MTD) <= 25 mg/week (<= 16 mg/week in Japan) in line with EULAR Recommendations 2016, and will be in principle maintained at the MTD from Week 12 onward. Also, the dosage of MTX will remain unchanged from Week 20 to 24 except for dose reduction/interruption due to an adverse drug reaction (ADR).
If SDAI remission is not achieved despite the dosage of MTX is maintained >= 10 mg/week at Week 24, a bDMARDs will be added to the treatment in line with EULAR Recommendations 2016. Subjects will subcutaneously receive ADA 40 mg as a bDMARDs every other week up to Week 48, and be randomized to a group in which the MTD of MTX (10 to 25 mg/week) will be maintained (ARM-2) and a group in which the dosage of MTX will be reduced to 6 to 8 mg/week (ARM-3). Then, the efficacy and safety will be evaluated.
Interventions/Control_3 Study treatment will start with MTX 6 to 8 mg/week, which will be promptly escalated to the maximum tolerable dose (MTD) <= 25 mg/week (<= 16 mg/week in Japan) in line with EULAR Recommendations 2016, and will be in principle maintained at the MTD from Week 12 onward. Also, the dosage of MTX will remain unchanged from Week 20 to 24 except for dose reduction/interruption due to an adverse drug reaction (ADR).
If SDAI remission is not achieved despite the dosage of MTX is maintained >= 10 mg/week at Week 24, a bDMARDs will be added to the treatment in line with EULAR Recommendations 2016. Subjects will subcutaneously receive ADA 40 mg as a bDMARDs every other week up to Week 48, and be randomized to a group in which the MTD of MTX (10 to 25 mg/week) will be maintained (ARM-2) and a group in which the dosage of MTX will be reduced to 6 to 8 mg/week (ARM-3). Then, the efficacy and safety will be evaluated.
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
18 years-old <=
Age-upper limit

Not applicable
Gender Male and Female
Key inclusion criteria 1) Patients aged >=18 years (>=20 years in Taiwan) at the time of informed consent
2) Patients who meet the 1987 revised ACR criteria or 2010 ACR/EULAR criteria
3) Patients who have RA within 2 years from initial diagnosis to informed consent
4) Patients who were previously untreated with MTX, JAK inhibitor, or bDMARDs
5) Patients who have disease activity of SDAI >11 at screening
6) Patients who are no need for concomitant use of DMARDs other than hydroxychloroquine (only in South Korea and Taiwan) and study drugs during the study as judged by principal investigator/sub-investigator at screening
7) Patients who are no need for concomitant use of corticoid steroid equivalent to >10 mg/day prednisolone during the study as judged by principal investigator/sub-investigator at screening.
8) Female of child-bearing potential who can use appropriate contraceptive during the study, female in whom time from menopause to informed consent is >=1 year, or female of no child-bearing potential through sterilization (bilateral tubal ligation, bilateral ovariectomy or hysterectomy, etc.)
9) Virile male who can use appropriate contraceptive during the study
10) Patients who can adequately understand this study procedures, and voluntarily consent in writing to take part in this study (consent of a legally-acceptable representative is also required for patients aged <20 years in Japan and aged <19 years in South Korea)
Key exclusion criteria 1) Patients who currently have a malignant tumor, except for non-melanoma forms of skin cancer limited within epidermis, and uterine cervix cancer limited within epidermis
2) Patients who have serious infections such as sepsis
3) Patients who have active tuberculosis
4) Patients who have a history or current complication of demyelinating disease such as multiple sclerosis
5) Patients who have congestive heart failure
6) Pregnant female, or female who intend to conceive during the study period
7) Patients who have bone marrow depression and whom investigator considered ineligible
8) Patients who have chronic liver disease and whom investigator considered ineligible, and who is positive for HBs antigen
9) Patients who have nephropathy and whom investigator considered ineligible
10) Lactating female
11) Patients who have pleural effusion or ascites
12) Patients with a known hypersensitivity to MTX or ADA
13) Patients otherwise whom principal investigator/sub-investigator considered medically ineligible to participate in the study
Target sample size 300

Research contact person
Name of lead principal investigator
1st name Yuko
Middle name
Last name Kaneko
Organization Keio University School of Medicine
Division name Division of Rheumatology, Department of Internal Medicine
Zip code 160-8582
Address 35, Shinanomachi, Shinjuku-ku, Tokyo, Japan
TEL 03-5363-3786
Email ykaneko@z6.keio.jp

Public contact
Name of contact person
1st name Hiroya
Middle name
Last name Tamai
Organization Keio University School of Medicine
Division name Division of Rheumatology, Department of Internal Medicine
Zip code 160-8582
Address 35, Shinanomachi, Shinjuku-ku, Tokyo, Japan
TEL 03-5363-3786
Homepage URL
Email h.tamai@keio.jp

Sponsor
Institute Keio University School of Medicine
Division of Rheumatology, Department of Internal Medicine
Institute
Department

Funding Source
Organization Eisai Co., Ltd.
Organization
Division
Category of Funding Organization Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor Eisai Co., Ltd.
Name of secondary funder(s)

IRB Contact (For public release)
Organization Certified Review Board of Keio
Address Tokyo 35, Shinanomachi, Shinjuku-ku, Tokyo, Japan
Tel 03-5363-3503
Email med-rinri-jimu@adst.keio.ac.jp

Secondary IDs
Secondary IDs YES
Study ID_1 jRCT1031180088
Org. issuing International ID_1 Japan Registry of Clinical Trials
Study ID_2 NCT03505008
Org. issuing International ID_2 ClinicalTrials.gov
IND to MHLW

Institutions
Institutions 慶應義塾大学病院(東京都)
東邦大学医療センター大橋病院(東京都)
日本医科大学付属病院(東京都)
国立病院機構 東京医療センター(東京都)
東北大学病院(宮城県)
千葉大学医学部附属病院(千葉県)
川崎市立 川崎病院(神奈川県)
東海大学医学部付属病院(神奈川県)
社会福祉法人 聖隷福祉事業団 総合病院 聖隷浜松病院(静岡県)
広島大学病院(広島県)
藤田医科大学病院(愛知県)
名古屋大学医学部附属病院(愛知県)

Other administrative information
Date of disclosure of the study information
2017 Year 12 Month 27 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
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 Open public recruiting
Date of protocol fixation
2017 Year 09 Month 21 Day
Date of IRB
2017 Year 12 Month 27 Day
Anticipated trial start date
2018 Year 04 Month 18 Day
Last follow-up date
2021 Year 01 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date
2017 Year 12 Month 27 Day
Last modified on
2019 Year 06 Month 30 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034918

Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
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