A Randomized, Double-Blind, Placebo-Controlled Study of Belimumab and Rituximab Combination Therapy for the Treatment of Diffuse Cutaneous Systemic Sclerosis

Plain English Summary

Belimumab and Rituximab Combination Therapy for the Treatment of Diffuse Cutaneous Systemic Sclerosis is a Phase 2 clinical trial sponsored by Hospital for Special Surgery, New York studying Systemic Sclerosis. This study is testing if a combination of Belimumab and Rituximab, along with a standard medication (Mycophenolate Mofetil), is more effective than a placebo in treating skin fibrosis in diffuse cutaneous systemic sclerosis. It is designed for adults aged 18-80 with diffuse cutaneous systemic sclerosis diagnosed within the last 3 years and significant skin thickening. Participants will receive either the investigational drug combination or a placebo, administered through injections and infusions, for 52 weeks, while continuing their background medication. Alternative treatments for systemic sclerosis include other immunosuppressants, anti-fibrotic agents, and supportive care, but this trial explores a novel combination for early-stage disease. The trial aims to enroll 30 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 18 and 80 years old and have been diagnosed with diffuse cutaneous systemic sclerosis within the last 3 years, with a specific score indicating skin thickening. You cannot join if you have had the disease for more than 3 years, have certain other autoimmune conditions, significant lung disease, or certain infections. Individuals with active infections, certain pre-existing medical conditions, or those who have recently used specific medications (like high-dose corticosteroids or other anti-fibrotic agents) may not be eligible. Women who are pregnant or breastfeeding, or not willing to use effective contraception, are excluded. This trial is studying Systemic Sclerosis, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how much the skin thickening improves after 12 months, which means patients could see a reduction in skin tightness and improved mobility. The specific primary outcome measures are: Primary Efficacy Outcome: Change in the ACR Revised CRISS at 12 months (12 months); Primary Safety Outcome: The proportion of participants who experience at least one Grade 3 or higher adverse event at or before 12 months (12 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for more effective treatments for diffuse cutaneous systemic sclerosis, aiming to improve skin fibrosis in early stages of this debilitating autoimmune disease. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Systemic Sclerosis, where improved treatment options are needed.

Investor Insight

This Phase 2 trial investigates a novel combination therapy for a rare autoimmune disease, potentially opening new treatment avenues and representing an investment in a specialized therapeutic area wi Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of Belimumab and Rituximab, and how they might interact with your current medications. Participation involves regular clinic visits for assessments, blood tests, and receiving study drug infusions and injections over a 52-week period. You will need to use effective birth control if you are of reproductive potential throughout the study. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 30 participants

Interventions

• DRUG: Belimumab — Belimumab decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. The background above provides a robust rationale for the investigation of belimumab in the treatment of dcSSc.
• DRUG: Rituximab — Rituxan® (rituximab) is a genetically engineered IgG1 kappa chimeric murine/human monoclonal antibody containing murine light- and heavy-chain variable region sequences and human constant region sequences. The antibody reacts specifically with the CD20 antigen found on the surface of malignant and normal B cells, and established B cell lines. Studies have shown that rituximab binds via its Fc domain to human complement and lyses lymphoid B cell lines by complement dependent cytotoxicity through
• OTHER: Placebo Subcutaneous Injection — Normal Saline
• OTHER: Placebo Infusion — Normal Saline
• DRUG: MMF — MMF belongs to a group of medicines known as immunosuppressive agents. It is used with other medicines to lower the body's natural immunity.

Primary Outcomes

• Primary Efficacy Outcome: Change in the ACR Revised CRISS at 12 months (12 months)
• Primary Safety Outcome: The proportion of participants who experience at least one Grade 3 or higher adverse event at or before 12 months (12 months)

Secondary Outcomes

• Proportion of patients who experience at least one grade 2 or higher adverse event (Baseline 1 through month 15)
• Number Infectious Adverse Events Across all Participants (Baseline 1 through month 15)
• Number Adverse Infusion Reactions Across all Participants (Baseline 1 through month 15)
• Number Injection Site Reactions Across all Participants (Baseline 1 through month 15)
• Number Adverse Events Across all Participants (Baseline 1 through month 15)

Full Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

1. Inability to render informed consent in accordance with institutional guidelines.
2. Disease duration of greater than 3 years.
3. Patients with mixed connective tissue disease or "overlap" unless the dominant features of the illness are diffuse systemic sclerosis.
4. Limited scleroderma.
5. Systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin.
6. The use of other anti-fibrotic agents including colchicine, D-penicillamine, or tyrosine kinase inhibitors (nilotinib, imatinib, dasatinib) in the month prior to enrollment.
7. 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.
8. 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.
9. 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.
10. Women not willing to use effective birth control for the duration of the study
11. Breastfeeding.
12. Participation in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study.
13. 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.
14. Grade 3 hypogammaglobulinemia
15. Have a significant IgG deficiency (IgG level \< 400 mg/dL)
16. Have an IgA deficiency (IgA level \< 10 mg/dL)
17. Have a historically positive HIV test or test positive at screening for HIV
18. Neutrophils \<1.5X10E9/L
19. Hepatitis status:

    1. Serologic evidence of current or past Hepatitis B (HB) infection based on the results of testing for HBsAg and HBcAb as follows:

1\. 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:

1. Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria)
2. Hospitalization for treatment of infection within 60 days of Day 0.
3. 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 

Trial Locations

• Hospital for Special Surgery, New York, New York, United States

Frequently Asked Questions

Related Conditions

• Systemic Sclerosis
• Diffuse Cutaneous Systemic Sclerosis
• Scleroderma
• Autoimmune Diseases
• Connective Tissue Diseases
• Fibrosis
• Immunosuppression
• Rheumatology
• Vasculitis
• Raynaud's Phenomenon

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