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

NCT04274257 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 2017019-11DX
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 4

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.

Conditions

Scleroderma, Systemic; Skin Sclerosis; Lung Fibrosis; Autoimmune Diseases; Collagen Diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (40)

• Change in percent FVC measured in respiratory function test

  From baseline to week 24

• Change in percent DLco measured in respiratory function test

  From baseline to week 24

• Change in TLC measured in respiratory function test

  From baseline to week 24

• Change in serum levels of KL-6

  From baseline to week 24

• Change in serum levels of SP-D

  From baseline to week 24

Study Arms (2)

Double-Blind Placebo

PLACEBO COMPARATOR

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

Double-Blind Rituximab

EXPERIMENTAL

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

Interventions

Double-Blind Placebo DRUG

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 Placebo

Double-Blind Rituximab DRUG

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.

Double-Blind Rituximab

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tokyo University: lead
• Japan Agency for Medical Research and Development: collaborator
• Zenyaku Kogyo Co., Ltd.: collaborator

Study Sites (4)

University of Fukui Hospital

Fukui, Japan

Location

Chukyo Hospital

Nagoya, Japan

Location

The University of Tokyo Hospital

Tokyo, 113-8655, Japan

Location

University of Tsukuba Hospital

Tsukuba, Japan

Location

Related Publications (3)

• Ebata S, Yoshizaki A, Oba K, Kashiwabara K, Ueda K, Uemura Y, Watadani T, Fukasawa T, Miura S, Yoshizaki-Ogawa A, Okiyama N, Kodera M, Hasegawa M, Sato S. Safety and efficacy of rituximab in systemic sclerosis (DESIRES): open-label extension of a double-blind, investigators-initiated, randomised, placebo-controlled trial. Lancet Rheumatol. 2022 Aug;4(8):e546-e555. doi: 10.1016/S2665-9913(22)00131-X. Epub 2022 Jun 28.

  PMID: 38294008 DERIVED

• Ebata S, Yoshizaki A, Oba K, Kashiwabara K, Ueda K, Uemura Y, Watadani T, Fukasawa T, Miura S, Yoshizaki-Ogawa A, Asano Y, Okiyama N, Kodera M, Hasegawa M, Sato S. Safety and efficacy of rituximab in systemic sclerosis (DESIRES): a double-blind, investigator-initiated, randomised, placebo-controlled trial. Lancet Rheumatol. 2021 Jul;3(7):e489-e497. doi: 10.1016/S2665-9913(21)00107-7. Epub 2021 May 26.

  PMID: 38279402 DERIVED

• 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.

  PMID: 35136981 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; Pulmonary Fibrosis; Autoimmune Diseases; Collagen Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases

Study Officials

• Ayumi Yoshizaki, MD, PhD

  Tokyo University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 18, 2020
• Study Start: December 4, 2017
• Primary Completion: May 9, 2019
• Study Completion: November 5, 2019
• Last Updated: February 18, 2020

Record last verified: 2020-02

Locations

JP (4)