A study of the efficacy and safety of belimumab compared to placebo in adults with systemic sclerosis-associated interstitial lung disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

22 May 2024 → ongoing

Decision date (initial)

2024-03-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

GSK

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of belimumab compared to placebo, in addition to standard therapy, on reducing the decline in lung volume in participants with dcSSc-ILD, as measured by change from baseline in FVC.

Secondary objectives 1

1. a. To evaluate the efficacy of belimumab compared to placebo, in addition to standard therapy, on reducing the extent of skin thickening in participants with dcSSc-ILD at Week 52. b. To evaluate the efficacy of belimumab compared to placebo, in addition to standard therapy, on reducing fatigue in participants with dcSSc-ILD. c. To evaluate the efficacy of belimumab compared to placebo, in addition to standard therapy, on SSc progression or mortality in participants with dcSSc-ILD.

Conditions and MedDRA coding

systemic sclerosis associated interstitial lung disease

Study design 1 period

Regulatory references

Scientific advice from competent authorities

National Medical Products Administration, European Medicines Agency, Pharmaceuticals And Medical Devices Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. 18 years of age or old1. 18 years of age or older. 2. Documented diagnosis of SSc as defined by the ACR/EULAR 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. 4. Presence of interstitial lung disease. 5. Evidence for active or progressive disease 6. 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. 7. 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. 8. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • Is a WONCBP as defined in Appendix 4: Contraceptive and Barrier Guidance. OR • Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%. 9. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.er. 2. Documented diagnosis of SSc as defined by the ACR/EULAR 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. 4. Presence of interstitial lung disease. 5. Evidence for active or progressive disease 6. 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. 7. 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. 8. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • Is a WONCBP as defined in Appendix 4: Contraceptive and Barrier Guidance. OR • Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%. 9. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion criteria 1

1. 1. Systemic sclerosis-like illness. 2. Pulmonary arterial hypertension. 3. SSc renal crisis within 6 months . 4. 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. 5. Obstructive pulmonary disease (pre-bronchodilator FEV1/FVC <0.7). 6. Significant allergies to human or murine proteins, humanized monoclonal antibodies, or contrast agents. 7. Clinically significant multiple or severe drug allergies. 8. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. 9. Breast cancer within the past 10 years. 10. ALT>2 x ULN. 11. Total bilirubin >1.5 x ULN (isolated total bilirubin >1.5 x ULN is acceptable if total bilirubin is fractionated and direct bilirubin <35%). 12. Cirrhosis or current unstable liver or biliary disease. 13. QTc >450 msec or QTc >480 msec in participants with bundle branch block. 14. Major surgery (including joint surgery) within 3 months or planned during the duration of the study. 15. An active infection, or a history of serious infections 16. Symptomatic herpes zoster within 3 months. 17. Confirmed diagnosis of active TB or untreated latent TB infection. 18. Confirmed PML or unexplained new-onset or deteriorating neurologic signs and symptoms. 19. Participants with PHQ-9 score ≥10 that in the opinion of a mental healthcare professional pose a serious suicide risk, or have any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months, or who in the investigator's judgment, pose a significant suicide risk. 20. Previous or planned major organ transplant. 21. Cytotoxic drugs such as, chlorambucil, nitrogen mustard, or other alkylating agents within 6 months. 22. Live vaccine(s) within 30 days or plans to receive such vaccines during the study. 23. Positive HIV antibody test. 24. Serologic evidence of Hepatitis B infection based on the results of testing for HBsAg, Anti-HBc and Anti-HBs as follows: • Patients positive for HBsAg are excluded. • Patients negative for HBsAg but positive for Anti-HBc, regardless of Anti-HBs antibody status, will require clarification of their status by testing for HBV DNA. o if HBV DNA is detectable, patients will be excluded from participation. o if HBV DNA is not detectable, patients will be eligible to enroll. 25. Positive hepatitis C antibody . 26. History of a primary immunodeficiency, or hypogammaglobulinaemia (IgG <400 mg/dL), or IgA deficiency (IgA <10 mg/dL). 27. Have a Grade 3 or greater neutropenia, defined as absolute neutrophil count <1000/mm3 (<1.0x10e9/L) based on the CTCAE v5.0.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change from baseline in FVC (mL) at Week 52.

Secondary endpoints 1

1. 1. Absolute change from baseline in mRSS at Week 52. 2. Absolute change from baseline in FACIT-Fatigue score at Week 52. 3. Time to SSc progression or death.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trails Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trails Call Center

Third parties 32

Locations

8 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 217 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications