A Study of the Efficacy and Safety of Rituximab in Participants With Systemic Sclerosis

Autoimmune Diseases Clinical Trial

— DesiReS  

Official title:

Double-Blind, Parallel-group Comparison, Investigators Initiated Phase II Clinical Trial of IDEC-C2B8 (Rituximab) in Patients With Systemic Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04274257
• Other study ID #: 2017019-11DX
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 4, 2017
• Est. completion date: November 5, 2019

Study information

• Verified date: February 2020
• Source: Tokyo University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the efficacy and safety of rituximab compared with placebo in SSc patients. This study consists of a 24-week, double-blind, placebo-controlled period followed by a 24-week active drug treatment period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: November 5, 2019
• Est. primary completion date: May 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Fulfill the diagnostic criteria for systemic sclerosis defined in the 2016 edition of the Clinical Practice Guidelines for Systemic Sclerosis and have an mRTSS of 2 (moderate) or higher for skin sclerosis

2. Aged 20 or older and younger than 80 at the time of consent

3. Have an expected survival of at least 6 months (and expected to allow 6 months of observation)

4. Fulfill the following criteria related to concomitant medications/therapies:

• Not received corticosteroids equivalent to more than 10 mg/day of prednisolone within 2 weeks before the start of study treatment; and

• Not received antifibrotic agents (like nintedanib, pirfenidone, tocilizumab), other investigational products, immunosuppressants (cyclophosphamide, mycophenolate mofetil, ciclosporin, tacrolimus, azathioprine, and mizoribine), high-dose intravenous immunoglobulin, or imatinib 4 weeks prior to the start of study treatment.

5. Provided written consent to participate in the study

Exclusion Criteria:

1. Present with pulmonary hypertension* associated with systemic sclerosis

*: The patient will undergo echocardiography during the pre-treatment observation period to exclude pulmonary hypertension. The patient will be required to undergo examination by an expert (eg, at the Department of Cardiovascular Medicine) if systolic pulmonary artery pressure exceeds 35 mmHg.

2. Have serious complications (eg, renal crisis) associated with systemic sclerosis (excluding interstitial pneumonia**)

**: Patients with interstitial pneumonia will be excluded if the criterion 3) below is met.

3. Have only poor respiratory reserve (%VC or %DLco, both calculated using the "estimation equation more suitable for Japanese," is less than 60% or 40%, respectively)

4. Known to have HIV antibodies

5. Have a positive result for any of the following: HBs antigen, HBs antibody, HBc antibody, and HCV antibody (this criterion does not apply to a positive test for hepatitis B clearly attributable to hepatitis vaccination)

6. Have serious bacterial/fungal infections

7. Have a serious liver disease (AST [GOT] or ALT[GPT] of = 300 IU)

8. Have a serious renal disease (serum creatinine = 2.0 mg/dL)

9. Have severe heart disease

10. Have active tuberculosis

11. Have any known malignancy or a history of malignancy within the past 5 years

12. Have a history of serious infections

13. Have a history of serious hypersensitivity or anaphylactic reactions to any component of rituximab or to mouse proteins

14. Pregnant, postpartum, and lactating women

15. Refuse to practice contraception from the time of consent to at least 12 months after study completion

16. Have any disease or physical/psychiatric conditions that make study participation difficult/inappropriate

17. Received other investigational products within 12 weeks prior to the study treatment or are participating in other clinical research/studies

18. Smoked within 12 weeks prior to the date of consent

19. Is determined by the investigator (or sub-investigator) to be ineligible for the study for any other reason

Related Conditions & MeSH terms

• Autoimmune Diseases
• Collagen Diseases
• Lung Fibrosis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Skin Sclerosis

Intervention

Drug:
• Double-Blind Placebo
The 4-week treatment period (four 375 mg/m2 doses at 1-week intervals) and subsequent 20-week follow-up period constitute one cycle of treatment. In the double-blind period, one cycle of placebo will be administered. In the active drug period, one additional cycle (rituximab) will be administered.
• Double-Blind Rituximab
The 4-week treatment period (four 375 mg/m2 doses at 1-week intervals) and subsequent 20-week follow-up period constitute one cycle of treatment. In the double-blind period, one cycle of rituximab will be administered. In the active drug period, one additional cycle (rituximab) will be administered.

Locations

Country	Name	City	State
Japan	University of Fukui Hospital	Fukui
Japan	Chukyo Hospital	Nagoya
Japan	The University of Tokyo Hospital	Tokyo
Japan	University of Tsukuba Hospital	Tsukuba

Sponsors (3)

Lead Sponsor	Collaborator
Tokyo University	Japan Agency for Medical Research and Development, Zenyaku Kogyo Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Modified Rodnan Total Skin Thickness Score (mRTSS) during double-blind period	Absolute change from pre-treatment observation period in skin sclerosis at week 24 of treatment in the double-blind phase, assessed by mRTSS. mRTSS ranging from 0 (normal) to 3 (severe skin thickening) across 17 different body parts. The total score is the sum of the individual skin scores for all these sites, and ranges from 0 to 51 units.	From baseline to week 24
Secondary	Change in percent FVC measured in respiratory function test		From baseline to week 24
Secondary	Change in percent DLco measured in respiratory function test		From baseline to week 24
Secondary	Change in TLC measured in respiratory function test		From baseline to week 24
Secondary	Change in serum levels of KL-6		From baseline to week 24
Secondary	Change in serum levels of SP-D		From baseline to week 24
Secondary	Change in serum levels of SP-A		From baseline to week 24
Secondary	Change in percentage of interstitial shadow in lungs by high-resolution computed tomography		From baseline to week 24
Secondary	Change in skin thickness measured following biopsy specimen		From baseline to week 24
Secondary	Change in HRQOL index measured using MOS 36 Item Short-Form Health Survey		From baseline to week 24
Secondary	Change in QOL index of SSc patients, assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI)		From baseline to week 24
Secondary	Change in serum antinuclear antibody titers		From baseline to week 24
Secondary	Change in serum levels of anti-centromere antibodies		From baseline to week 24
Secondary	Change in serum levels of anti-Scl-70 antibodies		From baseline to week 24
Secondary	Change in serum levels of anti-RNA polymerase III antibodies		From baseline to week 24
Secondary	Change in serum levels of anti-ssDNA antibodies		From baseline to week 24
Secondary	Change in serum levels of anti-dsDNA antibodies		From baseline to week 24
Secondary	Change in serum levels of anti-CL antibodies		From baseline to week 24
Secondary	Change in serum levels of anti-ß2-GP1 antibodies		From baseline to week 24
Secondary	Change in serum levels of lupus anticoagulant		From baseline to week 24
Secondary	Change in serum levels of anti-SS-A antibodies		From baseline to week 24
Secondary	Change in serum levels of anti-SS-B antibodies		From baseline to week 24
Secondary	Change in serum levels of anti-cANCA		From baseline to week 24
Secondary	Change in serum levels of anti-p-ANCA		From baseline to week 24
Secondary	Change in serum levels of anti-U1-RNP antibodies		From baseline to week 24
Secondary	Change in serum levels of IgG		From baseline to week 24
Secondary	Change in serum levels of IgM		From baseline to week 24
Secondary	Change in serum levels of IgA		From baseline to week 24
Secondary	Change in blood CD19+ B cell count		From baseline to week 24
Secondary	Change in blood CD20+ B cell count		From baseline to week 24
Secondary	Change in blood CD3+ T cell count		From baseline to week 24
Secondary	Expression of human anti-rituximab antibodies		From baseline to week 24
Secondary	Overall incidence, severity, causal relationship, and outcome of adverse events		From baseline to week 48
Secondary	Incidence of rituximab infusion reactions		From baseline to week 48
Secondary	PK profile of rituximab: Area under concentration-time curve from time 0 to final observation (AUC0-t)		From baseline to week 48
Secondary	PK profile of rituximab: maximum serum concentration after dosing (Cmax)		From baseline to week 48
Secondary	PK profile of rituximab: time to maximum concentration (tmax)		From baseline to week 48
Secondary	PK profile of rituximab: terminal half-life (t1/2)		From baseline to week 48
Secondary	PK profile of rituximab: mean residence time		From baseline to week 48
Secondary	PK profile of rituximab: clearance		From baseline to week 48
Secondary	PK profile of rituximab: volume of distribution		From baseline to week 48