A Study of the Efficacy and Safety of Belimumab in Adults With Systemic Sclerosis Associated Interstitial Lung Disease

Official title

A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate The Efficacy And Safety of Belimumab Administered Subcutaneously in Adults With Systemic Sclerosis Associated Interstitial Lung Disease (SSC-ILD)

Overview

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).

Interventions

• Biological Belimumab
  Belimumab will be administered.
• Other Placebo
  .Placebo will be administered.

Primary outcome measures

• Absolute change from baseline in Forced Vital Capacity (FVC) millilitre (mL) at Week 52 [Time frame: Baseline and Week 52]

Secondary outcome measures (12)

• Absolute change from baseline in modified Rodnan Skin Score (mRSS) at Week 52 [Time frame: Baseline and Week 52]
• Absolute change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at Week 52 [Time frame: Baseline and Week 52]
• Time to Systemic sclerosis (SSc) progression or death [Time frame: From the date of assignment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 52 Weeks]
• Absolute change from baseline in FVC percentage (%) predicted at Week 52 [Time frame: Baseline and Week 52]
• Relative decline from baseline in FVC (mL) greater than or equal to (≥)5% at Week 52 [Time frame: Baseline and Week 52]
• Relative decline from baseline in FVC (mL) ≥10% at Week 52 [Time frame: Baseline and Week 52]
• Absolute change from baseline in mRSS at Week 26 [Time frame: Baseline and Week 26]
• Proportion of participants achieving ≥20% increase in mRSS at Week 26 & 52 [Time frame: At Week 26 and Week 52]
• Absolute change from baseline in Quantitative interstitial lung disease - whole lung (QILD-WL) at Week 52 [Time frame: Baseline and Week 52]
• Absolute change from baseline in Quantitative lung fibrosis - whole lung (QLF-WL) at Week 52 [Time frame: Baseline and Week 52]
• Proportion of participants achieving ≥2% increase in QILD at Week 52 [Time frame: At Week 52]
• Absolute change from baseline in Carbon monoxide diffusing capacity (DLco) % predicted at Week 52 [Time frame: Baseline and Week 52]

Eligibility criteria

Inclusion criteria

• Participant is 18 years of age inclusive, or older at the time of signing the informed consent.
• Documented diagnosis of SSc as defined by the American College of Rheumatology / European League Against Rheumatism 2013 SSc classification criteria.
• Diffuse cutaneous disease, defined as presence of thickened skin with mRSS >0 over at least one skin area proximal to elbows and/or knees in addition to distal areas involvement on Day 1.
• Total mRSS ≥15 on Day 1.
• Evidence of interstitial lung disease on centrally read screening HRCT.
• Anticentromere antibody negative on central test at screening.
• Evidence for active or progressive disease
• Participant has an area of uninvolved or mildly thickened skin that, in the opinion of the investigator, would allow SC injection at the abdomen or the front, middle region of the thigh.
• Participant is capable and willing to self-administer the study medication or has a caregiver who is capable and willing to administer the study medication throughout the study.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

Is a Woman of Non-Childbearing Potential (WONCBP) OR Is a Woman of Childbearing Potential (WOCBP) and using a contraceptive method that is highly effective.

• Capable of giving signed informed consent.

Exclusion criteria

• Systemic sclerosis-like illness, including but not limited to localized scleroderma (morphoea), eosinophilic fasciitis, sclerodermoid graft-versus-host disease, fibro mucinous conditions (scleroedema, scleromyxoedema), scleroderma-like conditions that are associated with environmental chemical and drug exposure (e.g., toxic rapeseed oil, vinyl chloride, bleomycin, gadolinium-based contrast agents \[nephrogenic systemic fibrosis\], or due to metabolic disease).
• Primary diagnosis of a rheumatic autoimmune disease other than dcSSc, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, polymyositis, dermatomyositis, systemic vasculitis, Sjogren's syndrome, antisynthetase syndrome, or mixed connective tissue disease, as determined by the investigator.
• FVC ≤45% of predicted, or a DLco (corrected for hemoglobin) ≤40% of predicted or requiring supplemental oxygen at screening.
• Pulmonary arterial hypertension, as determined by the investigator at, or prior to first day of dosing (Day 1).
• SSc renal crisis within 6 months prior to the first day of dosing (Day 1).
• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
• Obstructive pulmonary disease (pre-bronchodilator FEV1/FVC <0.7).
• Significant emphysema on screening HRCT (extent of emphysema exceeds extent of ILD).
• Previous or planned major organ transplant (e.g., heart, lung, kidney, liver) or bone marrow transplant (e.g., autologous stem cell transplant).
• Treatment with biologic agents, such as intravenous immunoglobulin or monoclonal antibodies, including marketed drugs, within 3 months or 5 half-lives (whichever is longer) prior to dosing.
• Treatment with rituximab within 6 months prior to Day 1.
• Treatment with non-biologic systemic immunosuppressive medication, other than mycophenolate, methotrexate or azathioprine (including, but not limited to cyclosporine A, tacrolimus, leflunomide, oral or parenteral gold, Janus kinase (JAK) inhibitors) within 3 months prior to Day 1.
• Treatment with cyclophosphamide (oral or intravenous) within 6 months prior to Day 1.
• Use of anti-fibrotic agents including colchicine, D-penicillamine, pirfenidone or tyrosine kinase inhibitors (e.g., nintedanib, nilotinib, imatinib, dasatinib) within 4 weeks prior to Day 1.
• Cytotoxic drugs such as, chlorambucil, nitrogen mustard, or other alkylating agents within 6 months of Day 1.
• Treatment with IM or IV corticosteroids within 1 month prior to Day 1.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 25 centers

• GSK Investigational Site — Phoenix
• GSK Investigational Site — Scottsdale
• GSK Investigational Site — Scottsdale
• GSK Investigational Site — Tucson
• GSK Investigational Site — Los Angeles
• GSK Investigational Site — Los Angeles
• GSK Investigational Site — Los Angeles
• GSK Investigational Site — Upland
• … and 17 more centers

China · 17 centers

• GSK Investigational Site — Beijing
• GSK Investigational Site — Beijing
• GSK Investigational Site — Beijing
• GSK Investigational Site — Beijing
• GSK Investigational Site — Changchun
• GSK Investigational Site — Chengdu
• GSK Investigational Site — Chengdu
• GSK Investigational Site — Luzhou
• … and 9 more centers

Italy · 15 centers

Center list to be confirmed — check the primary protocol.

Japan · 9 centers

Center list to be confirmed — check the primary protocol.

Spain · 9 centers

Center list to be confirmed — check the primary protocol.

Brazil · 8 centers

• GSK Investigational Site — Belo Horizonte
• GSK Investigational Site — Curitiba
• GSK Investigational Site — Juiz de Fora
• GSK Investigational Site — Porto Alegre
• GSK Investigational Site — Porto Alegre
• GSK Investigational Site — Salvador
• GSK Investigational Site — São Paulo
• GSK Investigational Site — São Paulo

France · 6 centers

• GSK Investigational Site — Bobigny
• GSK Investigational Site — Brest
• GSK Investigational Site — Paris
• GSK Investigational Site — Paris
• GSK Investigational Site — Paris
• GSK Investigational Site — Toulouse

Israel · 6 centers

• GSK Investigational Site — Haifa
• GSK Investigational Site — Holon
• … and 4 more centers

Germany · 5 centers

• GSK Investigational Site — Cologne
• GSK Investigational Site — Düsseldorf
• GSK Investigational Site — Mainz
• GSK Investigational Site — Minden
• GSK Investigational Site — Tübingen

Greece · 5 centers

• GSK Investigational Site — Athens
• GSK Investigational Site — Athens
• GSK Investigational Site — Heraklion Crete
• GSK Investigational Site — Larissa
• GSK Investigational Site — Thessaloniki

South Korea · 5 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 5 centers

Center list to be confirmed — check the primary protocol.

Australia · 4 centers

• GSK Investigational Site — Liverpool
• GSK Investigational Site — Adelaide
• GSK Investigational Site — Woodville
• GSK Investigational Site — Fitzroy

Mexico · 4 centers

Center list to be confirmed — check the primary protocol.

Argentina · 3 centers

• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Ciudad Autonoma Buenos Aires
• GSK Investigational Site — Ciudad Autonoma de Buenos Aire

Belgium · 2 centers

• GSK Investigational Site — Ghent
• GSK Investigational Site — Liège

Denmark · 2 centers

• GSK Investigational Site — Aarhus
• GSK Investigational Site — Odense C

Finland · 1 center

• GSK Investigational Site — Turku

Publications

• Lescoat A, Lecureur V, Gudjonsson JE, Khanna D. Systemic sclerosis: pathogenic mechanisms and their implications for treatment. Semin Immunopathol. 2025 Nov 11;47(1):39. doi: 10.1007/s00281-025-01065-6. PMID 41217519

Identifiers

NCT: NCT05878717 · 218224 · 2023-503219-14-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗