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

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

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.

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