Belimumab and Rituximab Combination Therapy for the Treatment of Diffuse Cutaneous Systemic Sclerosis

  • End date
    Jun 30, 2024
  • participants needed
  • sponsor
    Hospital for Special Surgery, New York
Updated on 7 October 2022
immunosuppressive agents
autoimmune disease
progressive systemic sclerosis
raynaud's syndrome
diffuse cutaneous systemic sclerosis


This is a 52 week, single center, randomized, double-blind, placebo-controlled study.

After patients maintain a stable dose of Mycophenolate Mofetil (MMF) for at least 1 month, they will be randomized to treatment with either Belimumab & Rituximab or placebo.Patients in both groups will be on background MMF for the entirety of the study. Belimumab will be administered subcutaneously and Rituximab intravenously. Placebo injections and infusions will be of normal saline. Randomization will be done in a 2:1 manner to favor the treatment group. It is hypothesized that that Rituximab and Belimumab combination therapy with Mycophenolate Mofetil background therapy will improve fibrosis in SSc skin when compared to treatment with placebo and Mycophenolate Mofetil in a group of patients with early dcSSc.


The specific objectives of this study are to:

  1. Determine whether rituximab/belimumab/mmf is safe and tolerable in the treatment of patients with early diffuse cutaneous (dc)SSc when compared to patients treated with placebo/placebo/mmf, as assessed by comparison of adverse and serious adverse effects. In this study stand of care will be protocolized as mycophenolate mofetil.
  2. Determine whether rituximab/belimumab/mmf is more effective than placebo/placebo/mmf, as measured by change in CRISS, which is a composite outcome measure provisionally endorsed by the ACR for scleroderma clinical trials. It incorporates change in the mRSS, FVC percent predicted, physician and patient global assessments, and HAQ-DI. Additionally, hemoglobin corrected diffusion capacity (DLCO), Medsger Severity Scale (MSS), and by other physician and patient derived outcome measures will be used.
  3. Determine the biological activity of rituximab/belimumab/mmf vs placebo/placebo/mmf as assessed by effect on histology of skin, gene expression of skin and blood, change in B-Cell profiles including assessment of B regulatory cells, and effect on serological and cutaneous biomarkers of disease activity.

Condition Systemic Sclerosis
Treatment Rituximab, MMF, Placebo infusion, belimumab, Placebo Subcutaneous Injection
Clinical Study IdentifierNCT03844061
SponsorHospital for Special Surgery, New York
Last Modified on7 October 2022


Yes No Not Sure

Inclusion Criteria

Age greater than or equal to eighteen years and less than or equal to 80
Classification of systemic sclerosis (SSc), as defined using the 2013 American College of Rheumatology/European Union League Against Rheumatism classification of SSc
Diagnosis of dcSSc, as defined by LeRoy and Medsger
Disease duration of less than or equal to 3 years as defined by the date of onset of the first non-Raynaud's symptom
A modified Rodnan Skin Score (mRSS) of > 14

Exclusion Criteria

Inability to render informed consent in accordance with institutional guidelines
Disease duration of greater than 3 years
Patients with mixed connective tissue disease or "overlap" unless the dominant features of the illness are diffuse systemic sclerosis
Limited scleroderma
Systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin
The use of other anti-fibrotic agents including colchicine, D-penicillamine, or tyrosine kinase inhibitors (nilotinib, imatinib, dasatinib) in the month prior to enrollment
Use in the prior month of corticosteroids at doses exceeding the equivalent of prednisone 10 mg daily. Use of corticosteroid at < 10 mg of prednisone can continue during the course of the study
Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for this study such as uncontrollable CHF, arrhythmia, severe pulmonary or systemic hypertension, severe GI involvement, hepatic impairment, serum creatinine of greater than 2.0, active infection, severe diabetes, unstable atherosclerotic cardiovascular disease, malignancy, HIV, or severe peripheral vascular disease
A positive pregnancy test at entry into this study. Men and women with reproductive potential will be required to use effective means of contraception through the course of the study, such as (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) double-barrier methods (such as a condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository)(3) an intrauterine device (IUD) or intrauterine system (IUS) (4) estrogenic vaginal ring (5) percutaneous contraceptive patches, or (6) implants of levonorgestrel or etonogestrel. Approved hormonal contraceptives (such as birth control pills, patches, implants or injections) may interact with and reduce the effectiveness of MMF so women receiving MMF who are using oral contraceptives for birth control should employ an additional method (e.g. barrier method). Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use
Women not willing to use effective birth control for the duration of the study
Participation in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study
The presence of severe lung disease as defined by a diffusion capacity of less than 30% of predicted or requiring supplemental oxygen and forced vital capacity (FVC) of less than 45% of predicted
Grade 3 hypogammaglobulinemia
Have a significant IgG deficiency (IgG level < 400 mg/dL)
Have an IgA deficiency (IgA level < 10 mg/dL)
Have a historically positive HIV test or test positive at screening for HIV
Neutrophils <1.5X10E9/L
Hepatitis status
Serologic evidence of current or past Hepatitis B (HB) infection based on the results of testing for HBsAg and HBcAb as follows
Patients positive for HBsAg or HBcAb are excluded b) Positive test for Hepatitis C antibody 20. Known active bacterial, viral, fungal, mycobacterial, or other infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening 21. Infection history
Currently on any suppressive therapy for a chronic infection (such as tuberculosis
Hospitalization for treatment of infection within 60 days of Day 0
pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and
Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 60 days of Day 0 22. Suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes zoster and atypical mycobacteria) 23. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications 24. Prior use of Belimumab, Rituximab, or other B-Cell depleting therapies ever 25. The use of other biologics including TNF inhibitors, abatacept, or tocilizumab within the washout period below for each particular drug
atypical mycobacteria)
Tocilizumab - 1 month for patients on 2mg/kg or 4 mg/kg. 2 months for patients
on 8mg/kg
Cyclophosphamide (oral or IV) - 3 months. Abatacept - 2.5 months. TNF
Inhibitors : Etanercept - 1 mo, Infliximab - 2 mo, Adalimumab - 2.5 mo. Any
biologic investigational agent (e.g., abetimus sodium, anti CD40L antibody
BG9588/ IDEC 131) - 365 days prior to belimumab
Any non-biologic investigational agent - 30 days prior to belimumab
Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, pose a significant suicide risk
Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0
History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies 29. Live vaccines within 30 days prior to baseline 30. Have a history of malignant neoplasm within the last 5 years with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years 31. Have a history of a primary immunodeficiency 32. Have any other clinically significant abnormal laboratory value in the opinion of the investigator 33. Have any intercurrent significant medical or psychiatric illness that the investigator considers would make the candidate unsuitable for the study 34. Non English speakers
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note