Clinical trial NCT05878717: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Systemic Sclerosis Associated Interstitial Lung Disease
Scleroderma, Systemic
Keywords: Monoclonal antibody
Autoimmune connective tissue disease
Skin
lung
systemic sclerosis
scleroderma
interstitial lung disease
belimumab
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2023-05-26
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Absolute change from baseline in Forced Vital Capacity (FVC) millilitre (mL) at Week 52
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: Absolute change from baseline in modified Rodnan Skin Score (mRSS) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at Week 52
timeFrame: Baseline and Week 52
measure: Time to Systemic sclerosis (SSc) progression or death
timeFrame: 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
measure: Absolute change from baseline in FVC percentage (%) predicted at Week 52
timeFrame: Baseline and Week 52
measure: Relative decline from baseline in FVC (mL) greater than or equal to (≥)5% at Week 52
timeFrame: Baseline and Week 52
measure: Relative decline from baseline in FVC (mL) ≥10% at Week 52
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in mRSS at Week 26
timeFrame: Baseline and Week 26
measure: Proportion of participants achieving ≥20% increase in mRSS at Week 26 & 52
timeFrame: At Week 26 and Week 52
measure: Absolute change from baseline in Quantitative interstitial lung disease - whole lung (QILD-WL) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in Quantitative lung fibrosis - whole lung (QLF-WL) at Week 52
timeFrame: Baseline and Week 52
measure: Proportion of participants achieving ≥2% increase in QILD at Week 52
timeFrame: At Week 52
measure: Absolute change from baseline in Carbon monoxide diffusing capacity (DLco) % predicted at Week 52
timeFrame: Baseline and Week 52
measure: Relative decline from baseline in DLco % predicted ≥15% at Week 52
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in Cough Numeric Rating Scale (NRS) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in Scleroderma Skin Patient-Reported Outcome (SSPRO) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in Short Form-36 Health Survey Questionnaire (SF-36) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in Patient Global Assessment of SSc Disease Activity (PtGA) at Week 52.
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in Physician global assessment (PhGA) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute change from baseline in Transition Dyspnea Index (TDI) at Week 52
timeFrame: Baseline and Week 52
measure: Number of participants with Adverse Events (AEs), Adverse Events of special interest (AESIs) and Serious AEs (SAEs) up to Week 52
timeFrame: Up to Week 52
measure: Absolute change from baseline in DLco % predicted at Week 52
timeFrame: Baseline and Week 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Upland
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Ann Arbor
country: United States
facility: GSK Investigational Site
state: Michigan
city: New Brunswick
country: United States
facility: GSK Investigational Site
state: New Jersey
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Potsdam
country: United States
facility: GSK Investigational Site
state: New York
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Denison
country: United States
facility: GSK Investigational Site
state: Texas
city: El Paso
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Liverpool
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Adelaide
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Woodville
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Fitzroy
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Liege
country: Belgium
facility: GSK Investigational Site
city: Belo Horizonte
country: Brazil
facility: GSK Investigational Site
city: Curitiba
country: Brazil
facility: GSK Investigational Site
city: Juiz de Fora
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Changchun
country: China
facility: GSK Investigational Site
city: Chengdu
country: China
facility: GSK Investigational Site
city: Chengdu
country: China
facility: GSK Investigational Site
city: Luzhou
country: China
facility: GSK Investigational Site
city: Mianyang
country: China
facility: GSK Investigational Site
city: Nanjing
country: China
facility: GSK Investigational Site
city: Nanjing
country: China
facility: GSK Investigational Site
city: Nanning
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shenyang
country: China
facility: GSK Investigational Site
city: Xi'an
country: China
facility: GSK Investigational Site
city: ZhuZhou
country: China
facility: GSK Investigational Site
city: Aarhus
country: Denmark
facility: GSK Investigational Site
city: Odense C
country: Denmark
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Bobigny cedex
country: France
facility: GSK Investigational Site
city: Brest
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Toulouse Cedex 9
country: France
facility: GSK Investigational Site
city: Duesseldorf
country: Germany
facility: GSK Investigational Site
city: Koeln
country: Germany
facility: GSK Investigational Site
city: Minden
country: Germany
facility: GSK Investigational Site
city: Tuebingen
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Heraklion Crete
country: Greece
facility: GSK Investigational Site
city: Larissa
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Haifa
country: Israel
facility: GSK Investigational Site
city: Holon
country: Israel
facility: GSK Investigational Site
city: Kfar Saba
country: Israel
facility: GSK Investigational Site
city: Poriya
country: Israel
facility: GSK Investigational Site
city: Ramat Gan
country: Israel
facility: GSK Investigational Site
city: Tel Aviv
country: Israel
facility: GSK Investigational Site
city: Ancona
country: Italy
facility: GSK Investigational Site
city: Bari
country: Italy
facility: GSK Investigational Site
city: Cagliari
country: Italy
facility: GSK Investigational Site
city: Catania
country: Italy
facility: GSK Investigational Site
city: Ferrara
country: Italy
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Modena
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Orbassano TO
country: Italy
facility: GSK Investigational Site
city: Padova
country: Italy
facility: GSK Investigational Site
city: Pavia
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Verona
country: Italy
facility: GSK Investigational Site
city: Gunma
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokushima
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon Kyunggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Chihuahua
country: Mexico
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
city: Merida
country: Mexico
facility: GSK Investigational Site
city: Torreon
country: Mexico
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Bilbao
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: VigoPontevedra
country: Spain
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Leeds
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
References: