search
Back to results

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

Primary Purpose

Scleroderma, Systemic, Skin Sclerosis, Lung Fibrosis

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Double-Blind Placebo
Double-Blind Rituximab
Sponsored by
Tokyo University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Scleroderma, Systemic

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Fukui Hospital
  • Chukyo Hospital
  • The University of Tokyo Hospital
  • University of Tsukuba Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Double-Blind Placebo

Double-Blind Rituximab

Arm Description

Participants will receive double-blind matching placebo from baseline until week 24. Participants may then receive open-label rituximab from weeks 24 to 48.

Participants will receive double-blind rituximab from baseline until week 24. Participants may then receive open-label rituximab from weeks 24 to 48.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in percent FVC measured in respiratory function test
Change in percent DLco measured in respiratory function test
Change in TLC measured in respiratory function test
Change in serum levels of KL-6
Change in serum levels of SP-D
Change in serum levels of SP-A
Change in percentage of interstitial shadow in lungs by high-resolution computed tomography
Change in skin thickness measured following biopsy specimen
Change in HRQOL index measured using MOS 36 Item Short-Form Health Survey
Change in QOL index of SSc patients, assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI)
Change in serum antinuclear antibody titers
Change in serum levels of anti-centromere antibodies
Change in serum levels of anti-Scl-70 antibodies
Change in serum levels of anti-RNA polymerase III antibodies
Change in serum levels of anti-ssDNA antibodies
Change in serum levels of anti-dsDNA antibodies
Change in serum levels of anti-CL antibodies
Change in serum levels of anti-β2-GP1 antibodies
Change in serum levels of lupus anticoagulant
Change in serum levels of anti-SS-A antibodies
Change in serum levels of anti-SS-B antibodies
Change in serum levels of anti-cANCA
Change in serum levels of anti-p-ANCA
Change in serum levels of anti-U1-RNP antibodies
Change in serum levels of IgG
Change in serum levels of IgM
Change in serum levels of IgA
Change in blood CD19+ B cell count
Change in blood CD20+ B cell count
Change in blood CD3+ T cell count
Expression of human anti-rituximab antibodies
Overall incidence, severity, causal relationship, and outcome of adverse events
Incidence of rituximab infusion reactions
PK profile of rituximab: Area under concentration-time curve from time 0 to final observation (AUC0-t)
PK profile of rituximab: maximum serum concentration after dosing (Cmax)
PK profile of rituximab: time to maximum concentration (tmax)
PK profile of rituximab: terminal half-life (t1/2)
PK profile of rituximab: mean residence time
PK profile of rituximab: clearance
PK profile of rituximab: volume of distribution

Full Information

First Posted
February 13, 2020
Last Updated
February 15, 2020
Sponsor
Tokyo University
Collaborators
Japan Agency for Medical Research and Development, Zenyaku Kogyo Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT04274257
Brief Title
A Study of the Efficacy and Safety of Rituximab in Participants With Systemic Sclerosis
Acronym
DesiReS
Official Title
Double-Blind, Parallel-group Comparison, Investigators Initiated Phase II Clinical Trial of IDEC-C2B8 (Rituximab) in Patients With Systemic Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
December 4, 2017 (Actual)
Primary Completion Date
May 9, 2019 (Actual)
Study Completion Date
November 5, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tokyo University
Collaborators
Japan Agency for Medical Research and Development, Zenyaku Kogyo Co., Ltd.

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Scleroderma, Systemic, Skin Sclerosis, Lung Fibrosis, Autoimmune Diseases, Collagen Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Double-Blind Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive double-blind matching placebo from baseline until week 24. Participants may then receive open-label rituximab from weeks 24 to 48.
Arm Title
Double-Blind Rituximab
Arm Type
Experimental
Arm Description
Participants will receive double-blind rituximab from baseline until week 24. Participants may then receive open-label rituximab from weeks 24 to 48.
Intervention Type
Drug
Intervention Name(s)
Double-Blind Placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Double-Blind Rituximab
Intervention Description
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 Measure Information:
Title
Change in Modified Rodnan Total Skin Thickness Score (mRTSS) during double-blind period
Description
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.
Time Frame
From baseline to week 24
Secondary Outcome Measure Information:
Title
Change in percent FVC measured in respiratory function test
Time Frame
From baseline to week 24
Title
Change in percent DLco measured in respiratory function test
Time Frame
From baseline to week 24
Title
Change in TLC measured in respiratory function test
Time Frame
From baseline to week 24
Title
Change in serum levels of KL-6
Time Frame
From baseline to week 24
Title
Change in serum levels of SP-D
Time Frame
From baseline to week 24
Title
Change in serum levels of SP-A
Time Frame
From baseline to week 24
Title
Change in percentage of interstitial shadow in lungs by high-resolution computed tomography
Time Frame
From baseline to week 24
Title
Change in skin thickness measured following biopsy specimen
Time Frame
From baseline to week 24
Title
Change in HRQOL index measured using MOS 36 Item Short-Form Health Survey
Time Frame
From baseline to week 24
Title
Change in QOL index of SSc patients, assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI)
Time Frame
From baseline to week 24
Title
Change in serum antinuclear antibody titers
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-centromere antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-Scl-70 antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-RNA polymerase III antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-ssDNA antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-dsDNA antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-CL antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-β2-GP1 antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of lupus anticoagulant
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-SS-A antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-SS-B antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-cANCA
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-p-ANCA
Time Frame
From baseline to week 24
Title
Change in serum levels of anti-U1-RNP antibodies
Time Frame
From baseline to week 24
Title
Change in serum levels of IgG
Time Frame
From baseline to week 24
Title
Change in serum levels of IgM
Time Frame
From baseline to week 24
Title
Change in serum levels of IgA
Time Frame
From baseline to week 24
Title
Change in blood CD19+ B cell count
Time Frame
From baseline to week 24
Title
Change in blood CD20+ B cell count
Time Frame
From baseline to week 24
Title
Change in blood CD3+ T cell count
Time Frame
From baseline to week 24
Title
Expression of human anti-rituximab antibodies
Time Frame
From baseline to week 24
Title
Overall incidence, severity, causal relationship, and outcome of adverse events
Time Frame
From baseline to week 48
Title
Incidence of rituximab infusion reactions
Time Frame
From baseline to week 48
Title
PK profile of rituximab: Area under concentration-time curve from time 0 to final observation (AUC0-t)
Time Frame
From baseline to week 48
Title
PK profile of rituximab: maximum serum concentration after dosing (Cmax)
Time Frame
From baseline to week 48
Title
PK profile of rituximab: time to maximum concentration (tmax)
Time Frame
From baseline to week 48
Title
PK profile of rituximab: terminal half-life (t1/2)
Time Frame
From baseline to week 48
Title
PK profile of rituximab: mean residence time
Time Frame
From baseline to week 48
Title
PK profile of rituximab: clearance
Time Frame
From baseline to week 48
Title
PK profile of rituximab: volume of distribution
Time Frame
From baseline to week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Aged 20 or older and younger than 80 at the time of consent Have an expected survival of at least 6 months (and expected to allow 6 months of observation) 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. Provided written consent to participate in the study Exclusion Criteria: 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. 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. 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) Known to have HIV antibodies 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) Have serious bacterial/fungal infections Have a serious liver disease (AST [GOT] or ALT[GPT] of ≥ 300 IU) Have a serious renal disease (serum creatinine ≥ 2.0 mg/dL) Have severe heart disease Have active tuberculosis Have any known malignancy or a history of malignancy within the past 5 years Have a history of serious infections Have a history of serious hypersensitivity or anaphylactic reactions to any component of rituximab or to mouse proteins Pregnant, postpartum, and lactating women Refuse to practice contraception from the time of consent to at least 12 months after study completion Have any disease or physical/psychiatric conditions that make study participation difficult/inappropriate Received other investigational products within 12 weeks prior to the study treatment or are participating in other clinical research/studies Smoked within 12 weeks prior to the date of consent Is determined by the investigator (or sub-investigator) to be ineligible for the study for any other reason
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ayumi Yoshizaki, MD, PhD
Organizational Affiliation
Tokyo University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Fukui Hospital
City
Fukui
Country
Japan
Facility Name
Chukyo Hospital
City
Nagoya
Country
Japan
Facility Name
The University of Tokyo Hospital
City
Tokyo
ZIP/Postal Code
113-8655
Country
Japan
Facility Name
University of Tsukuba Hospital
City
Tsukuba
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
35136981
Citation
Ebata S, Oba K, Kashiwabara K, Ueda K, Uemura Y, Watadani T, Fukasawa T, Miura S, Yoshizaki-Ogawa A, Yoshihide A, Yoshizaki A, Sato S. Predictors of rituximab effect on modified Rodnan skin score in systemic sclerosis: a machine-learning analysis of the DesiReS trial. Rheumatology (Oxford). 2022 Nov 2;61(11):4364-4373. doi: 10.1093/rheumatology/keac023.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs