UMIN-CTR Clinical Trial

Basic information
Public title	Double-Blind, parallel-group comparison, investigators initiated phase II clinical trial of IDEC-C2B8 (Rituximab) in patients with Systemic Sclerosis
Acronym	"D"oubl"e"-Blind, parallel-group compari"s"on, "i"nvestigators initiated phase II clinical trial of IDEC-C2B8 ("R"ituximab) in pati"e"nts with "S"ystemic sclerosis
Scientific Title	Double-Blind, parallel-group comparison, investigators initiated phase II clinical trial of IDEC-C2B8 (Rituximab) in patients with Systemic Sclerosis
Scientific Title:Acronym	"D"oubl"e"-Blind, parallel-group compari"s"on, "i"nvestigators initiated phase II clinical trial of IDEC-C2B8 ("R"ituximab) in pati"e"nts with "S"ystemic sclerosis
Region	Japan

Condition
Condition	systemic sclerosis
Classification by specialty	Clinical immunology Dermatology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The primary objective of the study is to assess efficacy and safety of IDEC-C2B8 (Rituximab) in patients with systemic sclerosis (SSc).
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	The absolute amount of change of dermal sclerosis from the pretreatment period at the 24th week after study drugs dosage in the double-blind phase by modified Rodnan Total Skin Thickness Score (mRTSS)
Key secondary outcomes	>Measured value of %FVC, %DLco and TLC with Respiratory Function Test >The change in KL-6, SP-A, SP-D as a serum marker of the interstitial pneumonia >The change in the disease severity of the interstitial pneumonia >The thickness of the histopathology of the skin (Only when the patient consent is obtained) >An evaluation of Health-Related Quality of Life (HRQOL) by MOS 36-Item Short-Form Health Survey (SF-36) >The QOL evaluation of the generalized scleroderma patient by Health Assessment Questionnaire Disability Index (HAQ-DI) >The hematological change of the SSc-related autoantibody and antinuclear antibody (an anticentromere antibody, anti-Scl-70 (anti-topoisomerase I), anti-RNA polymerase III, anti-single stranded DNA IgG antibody, anti-double stranded DNA IgG antibody, anti-cardiolipin antibody, anti-b2-glycoprotein antibody, LAC, anti-SS-A antibody, anti-SS-B antibody, c-ANCA, p-ANCA, anti-U1-RNP antibody) >The change of serum IgG, IgM, IgA >The change in the number of serum B cells (CD19-positive cells, CD20-positive cells) and T cell (CD3-cells) >The presence or absence of the expression of the human anti-chimeric antibody (HACA) Safety endpoints >The incidence, disease severity, causal relationship, an outcome of all adverse events >The incidence and disease severity of infusion reaction >The change in the clinical laboratory parameters, vital signs, body weight, the electrocardiogram and echocardiographic findings Other endpoints >Pharmacokinetic profiles >Calculate the following pharmacokinetic profile parameters: area under the concentration-time curve (AUC0-t), maximum drug concentration (Cmax), maximum drug concentration time (Tmax), half-life period (t1/2), mean residence time, clearance, distribution volume

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Test Drug; IDEC-C2B8 (actual drug)
Interventions/Control_2	Control Drug; IDEC-C2B8 (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	20 years-old <=
Age-upper limit	80 years-old >
Gender	Male and Female
Key inclusion criteria	1)Patients meeting the diagnostic criteria of SSc which a revised edition in systemic sclerosis medical examination and treatment guideline 2016; the SSc patients more than 2 (moderate) disease severity of the skin induration by mRTSS. 2)Patients who are at age of 20 years or older and younger than 80 years at informed consent 3)The expectancy for life and follow-up duration > 6 months 4)Patients who meet the following conditions about a co-administered drug/combination therapy; >>No history of a dose of >10 mg of prednisolone within 2 weeks prior to the first infusion in case of having been receiving the adrenocortical steroid therapy >>No history of the dose of antifibrotic drugs (Nintedanib, Pirfenidone, Tocilizumab), the Investigational New Drugs, the immunosuppressants (Cyclophosphamide, Mycophenolate mofetil, Ciclosporin, Tacrolimus, Azathioprine, Mizoribine), intravenous immunoglobulin and Imatinib within 4 weeks before study drugs dosage 5)Having provided written informed consent for participation in this study
Key exclusion criteria	1)Patients who have pulmonary hypertension with SSc >The echocardiography is performed during the pretreatment period in order to confirm the complication of pulmonary hypertension. A diagnosis of the specialty department such as cardiovascular department is carried out when the pulmonary artery systolic pressure by the Doppler ultrasonography is more than 35mm Hg. 2)Patients who have serious complications (the renal crisis) other than interstitial pneumonia >With regard to interstitial pneumonia, patients who meet with the following 3) criterion will be excluded. 3)Patients who were judged that there was not enough spare ability (Less than 60%VC or less than 40%DLco calculated by newly generated prediction equation for Japanese) 4)Patients who are proved to have an HIV antibody 5)Patients that the positivity was confirmed in more than one of the HBs antigen, the HBs antibody, the HBc and HCV antibodies 6)Have serious bacterial/fungal infections 7)Have serious lung disorder 8)Have serious kidney diseases 9)Have severe heart disease 10)Have active tuberculosis 11)Have the merger of the malignant tumor, or who have the history within past 5 years 12)Have the previous history of significant infection 13)With an ingredient of this agent or serious erethism for the product derived from mouse protein or the anamnesis of the anaphylactic reaction 14)Women who are pregnant, breast feeding or positive of pregnant test 15)Patients who do not attempt to do contraception during the study period (until at least 12 months after the study end) 16)Have the disease, body condition and mental condition which make the study enforcement more difficult 17)Were administered the other investigational product within 12 weeks of the entry, or Patients who are participating in the other clinical study 18)Smoked within 12 weeks before the informed consent 19)Other patients who were judged ineligible by the study investigator
Target sample size	56

Research contact person
Name of lead principal investigator	1st name Ayumi Middle name Last name Yoshizaki
Organization	The University of Tokyo Hospital
Division name	Department of Dermatology
Zip code	113-8655
Address	7-3-1,Hongo,Bunkyo-ku,Tokyo,113-8655,JAPAN
TEL	03-5800-8861
Email	yoshizakiay-der@h.u-tokyo.ac.jp

Public contact
Name of contact person	1st name Ayumi Middle name Last name Yoshizaki
Organization	The University of Tokyo Hospital
Division name	Department of Dermatology
Zip code	113-8655
Address	7-3-1,Hongo,Bunkyo-ku,Tokyo,113-8655,JAPAN
TEL	03-5800-8661
Homepage URL
Email	yoshizakiay-der@h.u-tokyo.ac.jp

Sponsor
Institute	The University of Tokyo Hospital
Institute
Department

Funding Source
Organization	Japan Agency Medical Research and Development
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor	University of Fukui Hospital University of Tsukuba Hospital Cyukyo Hospital
Name of secondary funder(s)	ZENYAKU KOGYO CO.,LTD.

IRB Contact (For public release)
Organization	The University of Tokyo Hospital, Institutional Review Board
Address	7-3-1 Hongo, Bunkyo-ku, Tokyo
Tel	03-5800-8743
Email	rtx-office@umin.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	東京大学医学部附属病院（東京都）

Other administrative information
Date of disclosure of the study information	2017 Year 11 Month 28 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	Completed
Date of protocol fixation	2017 Year 10 Month 25 Day
Date of IRB	2017 Year 10 Month 25 Day
Anticipated trial start date	2017 Year 11 Month 28 Day
Last follow-up date	2019 Year 11 Month 05 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 11 Month 27 Day
Last modified on	2020 Year 09 Month 29 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034416