Belimumab for Systemic Sclerosis Interstitial Lung Disease

(BLISSc-ILD Trial)

Recruiting at 155 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: GlaxoSmithKline

Must be taking: Mycophenolate, Methotrexate, Azathioprine

Must not be taking: Biologics, Rituximab, Cyclophosphamide, Corticosteroids

Disqualifiers: Pulmonary hypertension, SSc renal crisis, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether belimumab, a medication, can improve lung function and overall quality of life for individuals with systemic sclerosis interstitial lung disease (SSc-ILD). Researchers aim to determine if belimumab outperforms a placebo (a non-active substance) when added to the usual treatment for this condition. The study also examines belimumab's effects on symptoms like skin thickening and fatigue. Individuals diagnosed with systemic sclerosis, exhibiting thickened skin and lung issues, might be suitable candidates for this trial. As a Phase 2 trial, this research measures belimumab's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must stop taking biologic agents, rituximab, non-biologic systemic immunosuppressive medications (except mycophenolate, methotrexate, or azathioprine), cyclophosphamide, anti-fibrotic agents, cytotoxic drugs, and corticosteroids for specific periods before starting the trial.

Is there any evidence suggesting that belimumab is likely to be safe for humans?

Research has shown that belimumab is generally safe for patients. In past studies on systemic sclerosis (a connective tissue disease), belimumab demonstrated a good safety record. Participants mostly experienced mild to moderate side effects, such as headaches and nausea, while serious side effects were rare.

The FDA has already approved belimumab for treating lupus, which supports its safety. However, treatments can affect people differently, and this trial aims to learn more about how belimumab works for lung disease related to systemic sclerosis (SSc-ILD).

Anyone considering joining a clinical trial should discuss the possible risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for systemic sclerosis?

Unlike the standard treatments for systemic sclerosis interstitial lung disease, which often involve immunosuppressants like cyclophosphamide or mycophenolate mofetil, belimumab works differently by targeting and inhibiting a specific protein called B-lymphocyte stimulator (BLyS). This action helps reduce the survival of B cells, which play a crucial role in the autoimmune activity behind the disease. Researchers are excited about belimumab because it offers a more precise way to modulate the immune system, potentially leading to improved outcomes with fewer side effects compared to broader immunosuppression.

What evidence suggests that belimumab might be an effective treatment for systemic sclerosis interstitial lung disease?

Research has shown that belimumab, which participants in this trial may receive, might improve lung function and reduce symptoms in people with SSc-ILD, a lung condition linked to systemic sclerosis. Studies have found that belimumab can also reduce skin thickening and improve quality of life by decreasing tiredness. Although one study did not find a significant change in skin thickening, belimumab has been effective for similar conditions. This suggests it might help with the lung and skin problems seen in SSc-ILD. While more research is needed, belimumab appears promising for those with this condition. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

Adults with systemic sclerosis associated interstitial lung disease (SSc-ILD) who are not pregnant or breastfeeding, can self-administer medication or have a caregiver to do so, and meet specific criteria for skin thickening and lung involvement. Excluded are those with significant emphysema, recent major organ transplants, similar conditions caused by drugs/environmental factors, certain treatments like rituximab within the last 6 months, severe heart/lung/kidney diseases, other autoimmune disorders besides SSc-ILD.

Inclusion Criteria

You have signs of lung disease on a special X-ray test.

I am not pregnant or breastfeeding and either cannot become pregnant or am using effective birth control.

I have a suitable skin area for SC injection in my abdomen or thigh.

Exclusion Criteria

I haven't taken any strong chemotherapy drugs like chlorambucil in the last 6 months.

I have been diagnosed with an autoimmune disease, but not dcSSc.

My lung scans show more damage from emphysema than from ILD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belimumab or placebo in addition to standard therapy for systemic sclerosis associated interstitial lung disease

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belimumab

Trial Overview The trial is testing the effectiveness of belimumab versus placebo in improving lung function and reducing symptoms related to systemic sclerosis such as skin thickening and fatigue. Participants will receive either belimumab or a placebo alongside their standard therapy to see if there's an improvement in their condition.

How Is the Trial Designed?

Group I: Belimumab Experimental Treatment 1 Intervention

Participants will receive belimumab in addition to standard therapy.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo in addition to standard therapy.

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)

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a study of 576 patients with interstitial lung disease (ILD) related to systemic sclerosis, nintedanib significantly reduced the annual decline in forced vital capacity (FVC) compared to placebo, indicating its efficacy in slowing lung function deterioration.

While nintedanib showed benefits in lung function, it did not demonstrate significant improvements in other systemic sclerosis symptoms, and gastrointestinal side effects, particularly diarrhea, were more common in the nintedanib group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. Distler, O., Highland, KB., Gahlemann, M., et al.[2021]

Benlysta (belimumab) is the first new drug approved for systemic lupus erythematosus (SLE) in 50 years, providing a new treatment option for patients with this complex disease.

Clinical trials suggest that Benlysta is effective in reducing SLE activity and flares in patients who are antinuclear antibody-positive, potentially allowing for lower doses of background medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab and the clinical data. Shum, K., Askanase, A.[2021]

In a 52-week pilot study involving 20 patients with early diffuse cutaneous systemic sclerosis (dcSSc), treatment with belimumab alongside mycophenolate mofetil (MMF) showed a greater median decrease in skin thickness (MRSS) compared to placebo, although this difference was not statistically significant.

Both treatment groups experienced significant improvements in MRSS, and belimumab treatment was associated with a notable reduction in profibrotic gene expression, suggesting its potential mechanism of action in reducing fibrosis in dcSSc.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab for the Treatment of Early Diffuse Systemic Sclerosis: Results of a Randomized, Double-Blind, Placebo-Controlled, Pilot Trial. Gordon, JK., Martyanov, V., Franks, JM., et al.[2023]

Recent clinical trials have confirmed that immunomodulatory treatments are effective in managing interstitial lung disease (ILD) associated with systemic sclerosis (SSc), which can lead to improved clinical outcomes for patients.

There is a need for better methods to identify patient cohorts for clinical trials and for the discovery of biomarkers that could enable more personalized prevention and management strategies for SSc-ILD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological management of systemic sclerosis associated interstitial lung disease. Dixon, G., Adamali, I., Adamali, H., et al.[2023]

Recent randomized trials indicate that evidence-based algorithms can effectively identify systemic sclerosis patients at risk for lung disease, enabling better monitoring and management.

By recognizing different disease subsets, physicians can tailor treatment strategies that consider individual patient physiology and the effects of specific therapies, improving overall disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How should we treat vascular and fibrotic lung disease in scleroderma? Kravitz, JN., Strange, C.[2021]

In a study involving 364 patients with systemic lupus erythematosus (SLE), long-term treatment with belimumab combined with standard therapy demonstrated a stable or declining incidence of adverse events over 4 years, indicating a favorable safety profile.

The most common side effects were mild, such as arthralgia and upper respiratory infections, and serious infusion reactions were rare, suggesting that belimumab can be safely administered for extended periods in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. Merrill, JT., Ginzler, EM., Wallace, DJ., et al.[2013]

In a study of 18 patients with systemic sclerosis (SSc), treatment with cyclophosphamide and corticosteroids for one year led to significant improvements in lung function, with 14 out of 18 patients showing increased vital capacity (VC) from 74% to 80% of predicted levels.

The treatment was particularly effective in patients with elevated inflammatory markers, where 11 out of 12 showed improved VC, suggesting that cyclophosphamide may specifically benefit those with active inflammation in pulmonary fibrosis associated with SSc.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide. Akesson, A., Scheja, A., Lundin, A., et al.[2019]

In a study of 839 patients with moderate-to-severe systemic lupus erythematosus (SLE), weekly subcutaneous belimumab (200 mg) significantly improved the SLE Responder Index (SRI4) response compared to placebo, with 61.4% of belimumab patients responding versus 48.4% of placebo patients.

Belimumab also reduced the risk and time to severe disease flares, with a median time of 171 days for belimumab compared to 118 days for placebo, while maintaining a safety profile similar to that of placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study. Stohl, W., Schwarting, A., Okada, M., et al.[2022]

Belimumab (Benlysta®) is an effective treatment for adults with active, autoantibody-positive systemic lupus erythematosus (SLE), particularly for those who have high disease activity despite standard therapy.

In multinational trials, patients receiving belimumab showed significantly higher rates of achieving an SLE Responder Index response at 52 weeks compared to those receiving a placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab: a guide to its use in systemic lupus erythematosus. Scott, LJ., Burness, CB., McCormack, PL.[2016]

In a long-term study involving 268 patients with systemic lupus erythematosus (SLE), belimumab demonstrated a stable safety profile, with treatment-related adverse events either remaining stable or declining over seven years.

Efficacy results showed significant improvements, with 75.6% of patients achieving a positive response on the SLE Responder Index by the midpoint of year 7, and a substantial reduction in disease activity as indicated by a 78.2% of patients achieving a ≥4-point reduction in the SELENA-SLEDAI score.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus: A Continuation of a Seventy-Six-Week Phase III Parent Study in the United States. Furie, RA., Wallace, DJ., Aranow, C., et al.[2019]

Belimumab showed efficacy in improving symptoms of Primary Sjögren's syndrome (pSS), with 37% of patients reporting reduced dryness and 77% showing improvement in glandular manifestations at week 28, effects that persisted to week 52.

The treatment was well tolerated and safely administered among the 28 patients studied, although the overall evidence is limited due to the small number of studies available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of belimumab in Primary Sjögren's syndrome: A systematic review. Álvarez-Rivas, N., Sang-Park, H., Díaz Del Campo, P., et al.[2021]

In Japan, a significant number of patients with systemic sclerosis (SSc) and SSc-associated interstitial lung disease (SSc-ILD) have been treated with biologics, with 3.5% of SSc patients and 5.0% of SSc-ILD patients receiving these therapies, primarily anti-IL-6 drugs like tocilizumab.

The study found that many patients continued biologic treatment for over a year, indicating a sustained use of these therapies, particularly after prior treatment with immunosuppressive drugs such as methotrexate and tacrolimus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of biologics for systemic sclerosis and systemic sclerosis-associated interstitial lung disease: Information from a Japanese hospital claims database. Narita, Y., Funatogawa, T., Mii, K., et al.[2023]

Belimumab is a monoclonal antibody that effectively targets and inhibits B-cell activating factor, leading to reduced B-cell levels and improved disease activity in patients with active systemic lupus erythematosus (SLE).

Clinical trials and post-marketing data indicate that belimumab is beneficial for lupus patients who continue to experience active disease despite receiving standard of care therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing experiences with belimumab in the treatment of SLE patients. Askanase, AD., Yazdany, J., Molta, CT.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05878717

NCT05878717 | A Study of the Efficacy and Safety ... The study will evaluate the effect of belimumab treatment on lung function as well as on extra-pulmonary disease manifestations, including skin thickening and ...

2. ard.bmj.com ard.bmj.com/content/82/Suppl_1/1668

AB0904 BELIMUMAB FOR THE TREATMENT OF ... We present the design of a global Phase 2/3 study that will test the efficacy and safety of SC belimumab in patients with SSc-ILD.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6590997/

Belimumab for the Treatment of Early Diffuse Systemic ... Because there was no statistically significant difference between the groups in the median change in MRSS, the primary efficacy end point was not met. In the ...

4. trials.arthritis.org trials.arthritis.org/trials/NCT05878717

A Study of the Efficacy and Safety of Belimumab in Adults With ... The study will evaluate the effect of belimumab treatment on lung function as well as on extra-pulmonary disease manifestations, including skin thickening and ...

5. rarediseaseadvisor.com rarediseaseadvisor.com/news/new-study-to-assess-belimumab-in-ssc-associated-interstitial-lung-disease/

New Study to Assess Belimumab in SSc-Associated ILD A study of the efficiency and safety study of belimumab compared to placebo in adults with systemic sclerosis associated interstitial lung disease (BLISSc-ILD).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06716606

NCT06716606 | A Study to Investigate the Long-term ... A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Systemic Sclerosis Associated Interstitial Lung Disease · Study Overview.