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

Scleroderma, Systemic Clinical Trial

— BLISSc-ILD  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05878717
• Other study ID #: 218224
• Secondary ID: EU CT Number2023
• Status: Recruiting
• Phase: Phase 3
• Start date: September 13, 2023
• Est. completion date: February 15, 2027

Study information

• Verified date: January 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: February 15, 2027
• Est. primary completion date: February 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Diseases
• Lung Diseases, Interstitial
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis

Intervention

Biological:
• Belimumab
Belimumab will be administered.

Other:
• Placebo
.Placebo will be administered.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Australia	GSK Investigational Site	Adelaide	South Australia
Australia	GSK Investigational Site	Fitzroy	Victoria
Australia	GSK Investigational Site	Liverpool	New South Wales
Australia	GSK Investigational Site	Woodville	South Australia
Belgium	GSK Investigational Site	Gent
Belgium	GSK Investigational Site	Leuven
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Curitba	Paraná
Brazil	GSK Investigational Site	Juiz de Fora	Minas Gerais
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Salvador	Bahía
Brazil	GSK Investigational Site	Sao Paulo	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Toronto	Ontario
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Luzhou
China	GSK Investigational Site	Mianyang
China	GSK Investigational Site	Nanjing
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Nanning	Guangxi
China	GSK Investigational Site	Nanning	Guangxi
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shenyang
China	GSK Investigational Site	Xian
China	GSK Investigational Site	ZhuZhou	Hunan
Denmark	GSK Investigational Site	Aarhus
Denmark	GSK Investigational Site	Køge
Denmark	GSK Investigational Site	Odense C
Finland	GSK Investigational Site	Turku
France	GSK Investigational Site	Bobigny
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Paris Cedex 13
France	GSK Investigational Site	Strasbourg
France	GSK Investigational Site	Toulouse cedex 9
Germany	GSK Investigational Site	Bad Abbach
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Minden	Nordrhein-Westfalen
Germany	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Wuppertal	Nordrhein-Westfalen
Greece	GSK Investigational Site	Athens	Attiki
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Heraklion-Crete
Greece	GSK Investigational Site	Larissa
Greece	GSK Investigational Site	Thessaloniki
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Kfar Saba
Israel	GSK Investigational Site	Tel Aviv
Israel	GSK Investigational Site	Tel Hashomer
Israel	GSK Investigational Site	Tiberias
Italy	GSK Investigational Site	Bari	Puglia
Italy	GSK Investigational Site	Catania	Sicilia
Italy	GSK Investigational Site	Cona (Ferrara)	Emilia-Romagna
Italy	GSK Investigational Site	Firenze
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Modena	Emilia-Romagna
Italy	GSK Investigational Site	Monserrato	Sardegna
Italy	GSK Investigational Site	Napoli
Italy	GSK Investigational Site	Orbassano	Piemonte
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Torrette	Marche
Italy	GSK Investigational Site	Verona
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon-si, Gyeonggi-do
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Merida	Yucatán
Mexico	GSK Investigational Site	Mexico City	Ciudad De Mexico
Mexico	GSK Investigational Site	Torreon	Coahuila
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Bilbao
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Vigo/ Pontevedra
United Kingdom	GSK Investigational Site	Edgbaston
United Kingdom	GSK Investigational Site	Leeds
United Kingdom	GSK Investigational Site	London
United States	GSK Investigational Site	Ann Arbor	Michigan
United States	GSK Investigational Site	Aurora	Colorado
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	El Paso	Texas
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Houston	Texas
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	New Brunswick	New Jersey
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Potsdam	New York
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	Upland	California
United States	GSK Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Denmark,  Finland,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute change from baseline in Forced Vital Capacity (FVC) millilitre (mL) at Week 52		Baseline and Week 52
Secondary	Absolute change from baseline in modified Rodnan Skin Score (mRSS) at Week 52	The modified Rodnan Skin Score (mRSS) is an evaluation of the patients skin thickness rated by clinical palpation using a 0 to 3 scale. The scale differentiates between 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness. The assessment is made across 17 pre-defined areas of the body, with total score ranging between 0 and 51. Higher scores indicate worse skin thickening.	Baseline and Week 52
Secondary	Absolute change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at Week 52	FACIT-fatigue is a validated patient-reported measure developed originally to assess fatigue in individuals with cancer and has subsequently been used and validated in numerous chronic conditions, including SSc. FACIT-Fatigue scores range from 0-52 (higher scores indicate less fatigue).	Baseline and Week 52
Secondary	Time to Systemic sclerosis (SSc) progression or death	SSc progression or death is defined as the time when major organ-based complications develop, or the participant dies.	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
Secondary	Absolute change from baseline in FVC percentage (%) predicted at Week 52		Baseline and Week 52
Secondary	Relative decline from baseline in FVC (mL) greater than or equal to (=)5% at Week 52		Baseline and Week 52
Secondary	Relative decline from baseline in FVC (mL) =10% at Week 52		Baseline and Week 52
Secondary	Absolute change from baseline in mRSS at Week 26	The modified Rodnan Skin Score (mRSS) is an evaluation of the patients skin thickness rated by clinical palpation using a 0 to 3 scale. The scale differentiates between 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness with inability to pinch the skin into a fold. The assessment is made across 17 pre-defined areas of the body and therefore the total score can range from 0 to 51. Higher scores indicate worse skin thickening.	Baseline and Week 26
Secondary	Proportion of participants achieving =20% increase in mRSS at Week 26 & 52		At Week 26 and Week 52
Secondary	Absolute change from baseline in Quantitative interstitial lung disease - whole lung (QILD-WL) at Week 52		Baseline and Week 52
Secondary	Absolute change from baseline in Quantitative lung fibrosis - whole lung (QLF-WL) at Week 52		Baseline and Week 52
Secondary	Proportion of participants achieving =2% increase in QILD at Week 52		At Week 52
Secondary	Absolute change from baseline in Carbon monoxide diffusing capacity (DLco) % predicted at Week 52		Baseline and Week 52
Secondary	Relative decline from baseline in DLco % predicted =15% at Week 52		Baseline and Week 52
Secondary	Absolute change from baseline in Cough Numeric Rating Scale (NRS) at Week 52	The cough NRS enables the participant to rate their cough on a defined scale from 0 to 10, where higher score indicating worse cough symptoms.	Baseline and Week 52
Secondary	Absolute change from baseline in Scleroderma Skin Patient-Reported Outcome (SSPRO) at Week 52	SSPRO a patient-reported outcome (PRO) instrument developed to assess the skin-related quality of life (QoL) in participants with SSc. SSPRO has 18 items that assess four SSc skin-related HRQoL domain (emotional effects, physical effects, physical limitations and social effects). The higher score indicates worse impact on QoL.	Baseline and Week 52
Secondary	Absolute change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 52	The HAQ-DI is a 26-question instrument assessing the degree of difficulty in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each question is scored 0-3 (where 0=without difficulty & 3=unable to do). Higher scores reflect worse disability	Baseline and Week 52
Secondary	Absolute change from baseline in Short Form-36 Health Survey Questionnaire (SF-36) at Week 52	The SF-36 yields an 8-scale profile of functional health and well-being scores as well as physical and mental component health summary scores. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.	Baseline and Week 52
Secondary	Absolute change from baseline in Patient Global Assessment of SSc Disease Activity (PtGA) at Week 52.	PtGA is a patient reported outcome scale designed to capture the participants overall assessment of their disease. The participants are asked to score their disease on a scale from 0 to 10 where higher score indicates higher severity	Baseline and Week 52
Secondary	Absolute change from baseline in Physician global assessment (PhGA) at Week 52	The PhGA is a score which enables the treating physician to rate the participants disease on a scale from 0 to 10, where higher score indicates greater severity.	Baseline and Week 52
Secondary	Absolute change from baseline in Transition Dyspnea Index (TDI) at Week 52	TDI assess dyspnea severity over 3 components: functional impairment, magnitude of task and magnitude of effort. Each component has 7 grades, ranging from -3 (major deterioration) to +3 (major improvement), which are summed to calculate a score, ranging between -9 and +9. The lower the score the more severely the participant is affected by dyspnea.	Baseline and Week 52
Secondary	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
Secondary	Absolute change from baseline in DLco % predicted at Week 52		Baseline and Week 52