Belimumab for Systemic Sclerosis Interstitial Lung Disease

(BLISSc-ILD Trial)

Recruiting at 136 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

Trial Summary

What is the purpose of this trial?

This study investigates the efficacy and safety of belimumab compared to placebo, in addition to standard therapy, for the treatment of participants with systemic sclerosis associated interstitial lung disease (SSc-ILD). The study will evaluate the effect of belimumab treatment on lung function as well as on extra-pulmonary disease manifestations, including skin thickening and general symptoms, such as fatigue, that impact quality of life (QoL).

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.

What data supports the effectiveness of the drug Belimumab for Systemic Sclerosis Interstitial Lung Disease?

Belimumab has been shown to be effective in reducing disease activity in patients with systemic lupus erythematosus (SLE), a condition where the immune system attacks the body's own tissues, similar to systemic sclerosis. This suggests it might help in other autoimmune conditions like systemic sclerosis, although direct evidence for interstitial lung disease is not available. ^{1 2 3 4 5}

Is belimumab safe for humans?

Belimumab, also known as Benlysta, has been studied for safety in conditions like systemic lupus erythematosus (SLE) and primary Sjögren's syndrome. Long-term studies show it is generally safe when used with standard therapy, although specific side effects can occur, and it is important to discuss these with a healthcare provider. ^{1 4 6 7 8}

How is the drug Belimumab unique for treating systemic sclerosis interstitial lung disease?

Belimumab is unique because it is a biologic drug that targets specific parts of the immune system, which is different from traditional treatments like cyclophosphamide that broadly suppress the immune system. This targeted approach may offer a novel way to manage systemic sclerosis interstitial lung disease by potentially reducing inflammation with fewer side effects. ^{9 10 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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 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 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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Belimumab for the Treatment of Early Diffuse Systemic Sclerosis: Results of a Randomized, Double-Blind, Placebo-Controlled, Pilot Trial. [2023]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Post-marketing experiences with belimumab in the treatment of SLE patients. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Belimumab and the clinical data. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Belimumab: a guide to its use in systemic lupus erythematosus. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. [2013]

7. United States 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. [2019]

8. Spain pubmed.ncbi.nlm.nih.gov

Efficacy of belimumab in Primary Sjögren's syndrome: A systematic review. [2021]

9. England 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. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Pharmacological management of systemic sclerosis associated interstitial lung disease. [2023]

12. England pubmed.ncbi.nlm.nih.gov

How should we treat vascular and fibrotic lung disease in scleroderma? [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. [2021]