Belimumab + Rituximab for Systemic Sclerosis
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Hospital for Special Surgery, New York
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Is the combination of Belimumab and Rituximab generally safe for humans?
Belimumab and Rituximab have been studied for safety in conditions like systemic lupus erythematosus and systemic sclerosis. Belimumab is generally considered safe, but like other immune-targeting drugs, it may increase the risk of infections. Rituximab has a long-term safety profile, but it can also increase infection risk and, in rare cases, has been associated with serious brain infections.
23567What data supports the effectiveness of the drug combination Belimumab and Rituximab for treating systemic sclerosis?
Research shows that Rituximab may help improve skin and lung function in systemic sclerosis patients, and Belimumab is approved for treating systemic lupus erythematosus, a related autoimmune condition. This suggests potential benefits for systemic sclerosis, although direct evidence is limited.
467910Will I have to stop taking my current medications?
The trial requires participants to stay on Mycophenolate Mofetil (MMF) throughout the study. If you are taking other medications, especially anti-fibrotic agents or certain biologics, you may need to stop them before joining the trial. The protocol does not specify for all medications, so it's best to discuss your current medications with the study team.
How is the drug combination of Belimumab, MMF, and Rituximab unique for treating systemic sclerosis?
This drug combination is unique because it targets B cells, which are part of the immune system, using two different mechanisms: Belimumab reduces B cell activation, while Rituximab depletes B cells. This dual approach may enhance the treatment's effectiveness in managing systemic sclerosis, a condition with limited standard treatment options.
14678Eligibility Criteria
This trial is for adults aged 18-80 with early diffuse cutaneous systemic sclerosis (dcSSc), diagnosed within the last 3 years, and a modified Rodnan Skin Score over 14. Participants must not have used certain drugs like Belimumab or Rituximab before, be free from severe infections or lung disease, and agree to use effective contraception.Inclusion Criteria
I have been diagnosed with diffuse cutaneous systemic sclerosis.
My first non-Raynaud's symptom appeared less than 3 years ago.
I am between 18 and 80 years old.
My condition is officially diagnosed as systemic sclerosis.
Exclusion Criteria
My condition has been diagnosed for over 3 years.
My condition is linked to exposure to certain toxic substances.
I have used Belimumab, Rituximab, or similar treatments before.
I have severe lung disease requiring extra oxygen or have low lung function.
I have a severe deficiency in my immune system's antibodies.
I have not used specific biologic drugs within their required washout periods.
I am on medication for a long-term infection like TB or herpes.
I have had or currently have Hepatitis B.
I have been diagnosed with limited scleroderma.
I have not received any live vaccines in the last 30 days.
I am unable to understand or sign the consent form.
My main condition is diffuse systemic sclerosis, not mixed connective tissue disease.
Participant Groups
The study tests if combining Belimumab and Rituximab improves skin fibrosis in dcSSc patients compared to placebo. All participants will continue their Mycophenolate Mofetil (MMF) treatment. The active drugs or placebos are given via subcutaneous injections and intravenous infusions over a year.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: MMF + Rituximab + BelimumabExperimental Treatment3 Interventions
Two infusions of 1000 mg of Rituximab, two weeks apart, weekly subcutaneous injections of 200 mg of Belimumab, and background MMF, 1000 -1500 mg twice daily for 48 weeks.
Group II: MMF + Placebo + PlaceboPlacebo Group3 Interventions
Two placebo infusions of normal saline, two weeks apart, weekly saline placebo subcutaneous injections, and background MMF, 1000 -1500 mg twice daily for 48 weeks.
Belimumab is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Benlysta for:
- Systemic lupus erythematosus (SLE)
🇪🇺 Approved in European Union as Benlysta for:
- Systemic lupus erythematosus (SLE)
🇨🇦 Approved in Canada as Benlysta for:
- Systemic lupus erythematosus (SLE)
🇯🇵 Approved in Japan as Benlysta for:
- Systemic lupus erythematosus (SLE)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Hospital for Special SurgeryNew York, NY
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Who is running the clinical trial?
Hospital for Special Surgery, New YorkLead Sponsor
GlaxoSmithKlineIndustry Sponsor
References
Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. [2022]The safety and potential efficacy of rituximab was examined in diffuse cutaneous systemic sclerosis (dc-SSc).
B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. [2022]To determine the safety of rituximab, to provide preliminary data regarding the potential efficacy of rituximab, and to investigate the effects of rituximab on autoimmunity and fibrosis in patients with diffuse cutaneous systemic sclerosis (dcSSc).
Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. [2013]To evaluate the safety profile of long-term belimumab therapy combined with standard therapy for systemic lupus erythematosus (SLE) in patients with active disease.
Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis. [2016]To assess the long-term efficacy and safety of single and multiple courses of rituximab therapy in systemic sclerosis (SSc) patients with and without lung disease.
B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use. [2022]The development of B cell-targeted biologics represents a major advance in the treatment of autoimmune rheumatic diseases. As with other immunosuppressive agents, risk of infection is a key clinical concern. This review summarises safety data from 15 years of experience of rituximab in autoimmune diseases with a particular focus on opportunistic infection and class-specific complications and infection risk. Rarely, cases of progressive multifocal leucoencephalopathy in rituximab-treated patients (5/100 000) have accumulated over time although no proven causal association has yet been shown. With repeat cycles of therapy, hypogammaglobulinaemia has been observed in a larger proportion of patients and is associated with increased risk of serious infections. The infection profile of the newer B cell-targeted agent, belimumab, in patients with active systemic lupus erythematosus is also discussed. Data from registries are needed to extend insights further and also to evaluate for any impact with the difference in mode of action of belimumab and infection risk in this population.
Targeted B cell therapies in the treatment of adult and pediatric systemic lupus erythematosus. [2017]Belimumab (Benlysta) is a fully-humanized monoclonal antibody that inhibits B-lymphocyte stimulator (also known as B cell activating factor) and was approved by the U.S. Federal Drug Administration and European Medicines Evaluation Agency for treatment in adults with autoantibody-positive systemic lupus erythematosus (SLE). Rituximab (Rituxan) is a chimeric anti-CD20 monoclonal antibody targeting B lymphocytes. This review discusses the key findings of the phase III trials in adults with SLE and of real-world use of belimumab and rituximab in the care of both adult and pediatric SLE patients. It highlights the safety profile of belimumab and rituximab and gives insight into the consideration of these therapies for specific SLE disease states. It concludes with a discussion of the current clinical trials investigating B cell therapies in specific SLE disease states and a look to the future, with ongoing clinical trials.
Belimumab for the Treatment of Early Diffuse Systemic Sclerosis: Results of a Randomized, Double-Blind, Placebo-Controlled, Pilot Trial. [2023]To assess the safety and efficacy of treatment with belimumab in patients with early diffuse cutaneous systemic sclerosis (dcSSc) treated with background mycophenolate mofetil (MMF).
Phase III, multicentre, randomised, double-blind, placebo-controlled, 104-week study of subcutaneous belimumab administered in combination with rituximab in adults with systemic lupus erythematosus (SLE): BLISS-BELIEVE study protocol. [2020]Belimumab, an anti-B-lymphocyte-stimulator antibody, is approved for the treatment of active, autoantibody-positive systemic lupus erythematosus (SLE). Rituximab, a B cell-depleting anti-CD20 antibody, remains in the SLE treatment armamentarium despite failed trials in lupus nephritis and extrarenal lupus. These biologics, which operate through complementary mechanisms, might result in an enhanced depletion of circulating and tissue-resident autoreactive B lymphocytes when administered together. Thus, belimumab and rituximab combination may be a highly effective treatment of SLE. This study aims to evaluate and compare the efficacy, safety and tolerability of subcutaneous (SC) belimumab and a single cycle of rituximab in patients with SLE with belimumab alone.
B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis. [2021]Recent data suggests that rituximab may favorably affect skin fibrosis and lung function in patients with systemic sclerosis. Based on experimental data suggesting a key role of B and T cells in scleroderma we aimed to explore the effect(s) of rituximab treatment on T cell subpopulations. Fifteen patients with scleroderma who received rituximab treatment and six who received standard treatment alone were recruited. Peripheral CD4+IL4+, CD4+INFγ+, CD4+IL17+ and CD4+CD40L+ T cells were assessed using flow cytometry. Using ELISA, serum levels of IL4 were assessed. Skin CD4+IL4+ T cells were assessed with confocal microscopy from skin biopsies. Following rituximab treatment skin CD4+IL4+ T cells obviously decreased as seen with confocal microscopy. Moreover, peripheral CD4+IL4+ T cells decreased significantly compared to those from patients who received standard treatment alone: median (IQR): 14.9 (22.63-12.88) vs 7.87 (12.81-4.9)%, p = 0.005 and 9.43 (19.53-7.50)% vs 14.86 (21.96-6.75)%, p = NS at baseline and 6 months later respectively, whereas there was no difference in serum IL4 levels. Peripheral CD4+CD40L+ T cells also decreased significantly following rituximab treatment compared to those from patients who received standard treatment alone: median (IQR): 17.78 (25.64-14.44)% vs 8.15 (22.85-3.08)%, p = 0.04 and 22.13 (58.77-8.20)% vs 72.11 (73.05-20.45)%, p = NS at baseline and 6 months later respectively. Furthermore, peripheral CD4+INFγ+ and CD4+IL17+ T cells revealed no differences following rituximab treatment. Our study demonstrates a link between rituximab treatment and CD4+IL4+ T cell decrease both in the skin and peripheral blood of patients with SSc.
Rituximab as a rescue treatment added on mycophenolate mofetil background therapy in progressive systemic sclerosis associated interstitial lung disease unresponsive to conventional immunosuppression. [2021]To test whether the use of rituximab (RTX) is effective and safe as a rescue therapy add-on treatment to mycophenolate (MMF) in patients with progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) in whom conventional immunosuppressants (IS) have failed.