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)

GlaxoSmithKline127 sites in 6 countries300 target enrollmentSeptember 13, 2023

ConditionsSystemic Sclerosis Associated Interstitial Lung Disease Scleroderma, Systemic

InterventionsBelimumab Placebo

Overview

Phase: Phase 2
Intervention: Belimumab
Conditions: Systemic Sclerosis Associated Interstitial Lung Disease
Sponsor: GlaxoSmithKline
Enrollment: 300
Locations: 127
Primary Endpoint: Absolute change from baseline in Forced Vital Capacity (FVC) millilitre (mL) at Week 52
Status: Recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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).

Registry

clinicaltrials.gov

Start Date

September 13, 2023

End Date

July 12, 2029

Last Updated

3 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

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
•Total mRSS ≥15 on Day
•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:

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.

Arms & Interventions

Belimumab

Participants will receive belimumab in addition to standard therapy.

Intervention: Belimumab

Placebo

Participants will receive placebo in addition to standard therapy.

Intervention: Placebo

Outcomes

Primary Outcomes

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

Time Frame: Baseline and Week 52

Secondary Outcomes

Absolute change from baseline in Scleroderma Skin Patient-Reported Outcome (SSPRO) at Week 52(Baseline and Week 52)
Absolute change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 52(Baseline and Week 52)
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)
Absolute change from baseline in Quantitative interstitial lung disease - whole lung (QILD-WL) at Week 52(Baseline and Week 52)
Proportion of participants achieving ≥2% increase in QILD at Week 52(At Week 52)
Absolute change from baseline in Carbon monoxide diffusing capacity (DLco) % predicted at Week 52(Baseline and Week 52)
Relative decline from baseline in DLco % predicted ≥15% at Week 52(Baseline and Week 52)
Absolute change from baseline in Cough Numeric Rating Scale (NRS) at Week 52(Baseline and Week 52)
Absolute change from baseline in Short Form-36 Health Survey Questionnaire (SF-36) 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)
Relative decline from baseline in FVC (mL) ≥10% at Week 52(Baseline and Week 52)
Absolute change from baseline in Quantitative lung fibrosis - whole lung (QLF-WL) at Week 52(Baseline and Week 52)
Absolute change from baseline in DLco % predicted at Week 52(Baseline and Week 52)
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)
Absolute change from baseline in mRSS at Week 26(Baseline and Week 26)
Proportion of participants achieving ≥20% increase in mRSS at Week 26 & 52(At Week 26 and Week 52)
Absolute change from baseline in Patient Global Assessment of SSc Disease Activity (PtGA) at Week 52.(Baseline and Week 52)
Absolute change from baseline in Physician global assessment (PhGA) at Week 52(Baseline and Week 52)
Absolute change from baseline in Transition Dyspnea Index (TDI) at Week 52(Baseline and Week 52)
Number of participants with Adverse Events (AEs), Adverse Events of special interest (AESIs) and Serious AEs (SAEs) up to Week 52(Up to Week 52)