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)

Official Summary

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).

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 300 participants

Study Arms

• Belimumab (EXPERIMENTAL)
  Participants will receive belimumab in addition to standard therapy.
• Placebo (PLACEBO_COMPARATOR)
  Participants will receive placebo in addition to standard therapy.

Interventions

• BIOLOGICAL: Belimumab — Belimumab will be administered.
• OTHER: Placebo — .Placebo will be administered.

Primary Outcomes

• Absolute change from baseline in Forced Vital Capacity (FVC) millilitre (mL) at Week 52 (Baseline and Week 52)

Secondary Outcomes

• Absolute change from baseline in modified Rodnan Skin Score (mRSS) at Week 52 (Baseline and Week 52)
• Absolute change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at Week 52 (Baseline and Week 52)
• Time to Systemic sclerosis (SSc) progression or death (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 (Baseline and Week 52)
• Relative decline from baseline in FVC (mL) greater than or equal to (≥)5% at Week 52 (Baseline and Week 52)

Eligibility Criteria

Inclusion Criteria:

1. Participant is 18 years of age inclusive, or older at the time of signing the informed consent.
2. Documented diagnosis of SSc as defined by the American College of Rheumatology / European League Against Rheumatism 2013 SSc classification criteria.
3. 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.
4. Total mRSS ≥15 on Day 1.
5. Evidence of interstitial lung disease on centrally read screening HRCT.
6. Anticentromere antibody negative on central test at screening.
7. Evidence for active or progressive disease
8. 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.
9. 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.
10. 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.
11. Capable of giving signed informed consent.

Exclusion Criteria:

1. 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).
2. 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.
3. FVC ≤45% of predicted, or a DLco (corrected for hemoglobin) ≤40% of predicted or requiring supplemental oxygen at screening.
4. Pulmonary arterial hypertension, as determined by the investigator at, or prior to first day of dosing (Day 1).
5. SSc renal crisis within 6 months prior to the first day of dosing (Day 1).
6. 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.
7. Obstructive pulmonary disease (pre-bronchodilator FEV1/FVC \<0.7).
8. Significant emphysema on screening HRCT (extent of emphysema exceeds extent of ILD).
9. Previous or planned major organ transplant (e.g., heart, lung, kidney, liver) or bone marrow transplant (e.g., autologous stem cell transplant).
10. 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.
11. Treatment with rituximab within 6 months prior to Day 1.
12. 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.
13. Treatment with cyclophosphamide (oral or intravenous) within 6 months prior to Day 1.
14. 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.
15. Cytotoxic drugs such as, chlorambucil, nitrogen mustard, or other alkylating agents within 6 months of Day 1.
16. Treatment with IM or IV corticosteroids within 1 month prior to Day 1.

Trial Locations

• GSK Investigational Site, Phoenix, Arizona, United States
• GSK Investigational Site, Scottsdale, Arizona, United States
• GSK Investigational Site, Scottsdale, Arizona, United States
• GSK Investigational Site, Tucson, Arizona, United States
• GSK Investigational Site, Los Angeles, California, United States
• GSK Investigational Site, Los Angeles, California, United States
• GSK Investigational Site, Los Angeles, California, United States
• GSK Investigational Site, Upland, California, United States
• GSK Investigational Site, Aurora, Colorado, United States
• GSK Investigational Site, Washington D.C., District of Columbia, United States
• ...and 10 more locations

Contact Information

• US GSK Clinical Trials Call Center — CONTACT
  Phone: 877-379-3718
  Email: GSKClinicalSupportHD@gsk.com
• EU GSK Clinical Trials Call Center — CONTACT
  Phone: +44 (0) 20 89904466
  Email: GSKClinicalSupportHD@gsk.com

More Systemic Sclerosis Associated Interstitial Lung Disease Trials

View all Systemic Sclerosis Associated Interstitial Lung Disease clinical trials