UMIN-CTR Clinical Trial

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

systemic sclerosis

Classification by specialty

Clinical immunology

Dermatology

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

The University of Tokyo Hospital

Institute

Department

Personal name

Organization

Japan Agency Medical Research and Development

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

University of Fukui Hospital
University of Tsukuba Hospital
Cyukyo Hospital

Name of secondary funder(s)

ZENYAKU KOGYO CO.,LTD.

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

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

東京大学医学部附属病院（東京都）

Date of disclosure of the study information

2017

Year

11

Month

28

Day

URL releasing protocol

Publication of results

Unpublished

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

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 related information

Registered date

2017

Year

11

Month

27

Day

Last modified on

2020

Year

09

Month

29

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034416