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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04274257
Recruitment Status : Completed
First Posted : February 18, 2020
Last Update Posted : February 18, 2020
Sponsor:
Collaborators:
Japan Agency for Medical Research and Development
Zenyaku Kogyo Co., Ltd.
Information provided by (Responsible Party):
Ayumi Yoshizaki, Tokyo University

Brief 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.

Condition or disease Intervention/treatment Phase
Scleroderma, Systemic Skin Sclerosis Lung Fibrosis Autoimmune Diseases Collagen Diseases Drug: Double-Blind Placebo Drug: Double-Blind Rituximab Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind, Parallel-group Comparison, Investigators Initiated Phase II Clinical Trial of IDEC-C2B8 (Rituximab) in Patients With Systemic Sclerosis
Actual Study Start Date : December 4, 2017
Actual Primary Completion Date : May 9, 2019
Actual Study Completion Date : November 5, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Scleroderma
Drug Information available for: Rituximab

Arm Intervention/treatment
Placebo Comparator: Double-Blind Placebo
Participants will receive double-blind matching placebo from baseline until week 24. Participants may then receive open-label rituximab from weeks 24 to 48.
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.


Experimental: Double-Blind Rituximab
Participants will receive double-blind rituximab from baseline until week 24. Participants may then receive open-label rituximab from weeks 24 to 48.
Drug: 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.





Primary Outcome Measures :
  1. Change in Modified Rodnan Total Skin Thickness Score (mRTSS) during double-blind period [ Time Frame: From baseline to week 24 ]
    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.


Secondary Outcome Measures :
  1. Change in percent FVC measured in respiratory function test [ Time Frame: From baseline to week 24 ]
  2. Change in percent DLco measured in respiratory function test [ Time Frame: From baseline to week 24 ]
  3. Change in TLC measured in respiratory function test [ Time Frame: From baseline to week 24 ]
  4. Change in serum levels of KL-6 [ Time Frame: From baseline to week 24 ]
  5. Change in serum levels of SP-D [ Time Frame: From baseline to week 24 ]
  6. Change in serum levels of SP-A [ Time Frame: From baseline to week 24 ]
  7. Change in percentage of interstitial shadow in lungs by high-resolution computed tomography [ Time Frame: From baseline to week 24 ]
  8. Change in skin thickness measured following biopsy specimen [ Time Frame: From baseline to week 24 ]
  9. Change in HRQOL index measured using MOS 36 Item Short-Form Health Survey [ Time Frame: From baseline to week 24 ]
  10. Change in QOL index of SSc patients, assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: From baseline to week 24 ]
  11. Change in serum antinuclear antibody titers [ Time Frame: From baseline to week 24 ]
  12. Change in serum levels of anti-centromere antibodies [ Time Frame: From baseline to week 24 ]
  13. Change in serum levels of anti-Scl-70 antibodies [ Time Frame: From baseline to week 24 ]
  14. Change in serum levels of anti-RNA polymerase III antibodies [ Time Frame: From baseline to week 24 ]
  15. Change in serum levels of anti-ssDNA antibodies [ Time Frame: From baseline to week 24 ]
  16. Change in serum levels of anti-dsDNA antibodies [ Time Frame: From baseline to week 24 ]
  17. Change in serum levels of anti-CL antibodies [ Time Frame: From baseline to week 24 ]
  18. Change in serum levels of anti-β2-GP1 antibodies [ Time Frame: From baseline to week 24 ]
  19. Change in serum levels of lupus anticoagulant [ Time Frame: From baseline to week 24 ]
  20. Change in serum levels of anti-SS-A antibodies [ Time Frame: From baseline to week 24 ]
  21. Change in serum levels of anti-SS-B antibodies [ Time Frame: From baseline to week 24 ]
  22. Change in serum levels of anti-cANCA [ Time Frame: From baseline to week 24 ]
  23. Change in serum levels of anti-p-ANCA [ Time Frame: From baseline to week 24 ]
  24. Change in serum levels of anti-U1-RNP antibodies [ Time Frame: From baseline to week 24 ]
  25. Change in serum levels of IgG [ Time Frame: From baseline to week 24 ]
  26. Change in serum levels of IgM [ Time Frame: From baseline to week 24 ]
  27. Change in serum levels of IgA [ Time Frame: From baseline to week 24 ]
  28. Change in blood CD19+ B cell count [ Time Frame: From baseline to week 24 ]
  29. Change in blood CD20+ B cell count [ Time Frame: From baseline to week 24 ]
  30. Change in blood CD3+ T cell count [ Time Frame: From baseline to week 24 ]
  31. Expression of human anti-rituximab antibodies [ Time Frame: From baseline to week 24 ]
  32. Overall incidence, severity, causal relationship, and outcome of adverse events [ Time Frame: From baseline to week 48 ]
  33. Incidence of rituximab infusion reactions [ Time Frame: From baseline to week 48 ]
  34. PK profile of rituximab: Area under concentration-time curve from time 0 to final observation (AUC0-t) [ Time Frame: From baseline to week 48 ]
  35. PK profile of rituximab: maximum serum concentration after dosing (Cmax) [ Time Frame: From baseline to week 48 ]
  36. PK profile of rituximab: time to maximum concentration (tmax) [ Time Frame: From baseline to week 48 ]
  37. PK profile of rituximab: terminal half-life (t1/2) [ Time Frame: From baseline to week 48 ]
  38. PK profile of rituximab: mean residence time [ Time Frame: From baseline to week 48 ]
  39. PK profile of rituximab: clearance [ Time Frame: From baseline to week 48 ]
  40. PK profile of rituximab: volume of distribution [ Time Frame: From baseline to week 48 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04274257


Locations
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Japan
University of Fukui Hospital
Fukui, Japan
Chukyo Hospital
Nagoya, Japan
The University of Tokyo Hospital
Tokyo, Japan, 113-8655
University of Tsukuba Hospital
Tsukuba, Japan
Sponsors and Collaborators
Tokyo University
Japan Agency for Medical Research and Development
Zenyaku Kogyo Co., Ltd.
Investigators
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Principal Investigator: Ayumi Yoshizaki, MD, PhD Tokyo University
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Responsible Party: Ayumi Yoshizaki, Principal Investigator, Tokyo University
ClinicalTrials.gov Identifier: NCT04274257    
Other Study ID Numbers: 2017019-11DX
First Posted: February 18, 2020    Key Record Dates
Last Update Posted: February 18, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Collagen Diseases
Autoimmune Diseases
Sclerosis
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents