A Study to Evaluate the Efficacy and Safety of GSK3915393 in Participants With Idiopathic Pulmonary Fibrosis (IPF)

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study (TRANSFORM) to Evaluate the Efficacy and Safety of GSK3915393 in Participants With Idiopathic Pulmonary Fibrosis (IPF)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06317285
• Other study ID #: 220929
• Secondary ID: 2023-509371-16-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 1, 2024
• Est. completion date: March 19, 2026

Study information

• Verified date: March 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

Idiopathic Pulmonary Fibrosis is a chronic lung disease which causes scarring of the lungs and difficulty in breathing. GSK3915393 is a new medicine, which is being tested in participants with IPF for the first time. The study will assess the safety and effectiveness of GSK3915393 in IPF participants.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: March 19, 2026
• Est. primary completion date: March 19, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants with IPF diagnosed within 5 years prior to screening based on the applicable American Thoracic Society (ATS)/ European Respiratory Society (ERS)/ Japanese Respiratory Society (JRS)/ Latin American Thoracic Society (ALAT) Guideline at the time of diagnosis.

• Centrally read chest High Resolution Computed Tomography (HRCT) obtained at screening or historical HRCT obtained within 12 months of screening that is consistent with Usual interstitial pneumonia (UIP) or probable UIP (if indeterminate HRCT finding, IPF may be confirmed locally by historical biopsy).

• FVC greater than or equal to (>=) 45 percent (%) of predicted normal.

• Diffusing Capacity (of Lung) for Carbon Monoxide (DLCO) >=25% of predicted normal corrected for hemoglobin (Hb).

• Prebronchodilator Forced Expiratory Volume in 1 second (FEV1)/FVC = 0.7.

• If receiving antifibrotics must be on stable dose of nintedanib or pirfenidone for at least 12 weeks prior to screening.

• If not currently receiving pirfenidone or nintedanib, participant must have stopped pirfenidone or nintedanib for at least 4 weeks prior to screening.

• Body weight =40 kilogram (kg) and body mass index within the range 18.5-35 kilogram per meter square (kg/m2) (inclusive).

• A female participant is eligible to participate if a woman of nonchildbearing potential (WONCBP)

• Capable of giving signed informed consent

Exclusion Criteria:

• Participants with Interstitial Lung Disease (ILD) associated with other known causes.

• Diagnosis of sarcoidosis or any systemic autoimmune disease (including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus and rheumatoid arthritis).

• Acute IPF exacerbation within 6 months prior to screening and/or during the screening period (investigator-determined).

• Clinically significant non-parenchymal lung disease (e.g., asthma, chronic obstructive pulmonary disease, cavitary or pleural diseases) at screening.

• Diagnosis of severe pulmonary hypertension (investigator-determined)

• Extent of emphysema is greater than the extent of fibrosis according to reported results from the most recent HRCT.

• History of previous lung transplant or recent major surgery (investigator-determined) within 12 weeks prior to screening or planned during the trial period. Registration on a transplant waiting list is allowed.

• Clinically significant respiratory tract infection (e.g., active tuberculosis, infectious pneumonia, Corona virus disease 2019 [COVID-19]) requiring treatment within 4 weeks prior to and/or during the screening period.

• Cigarette smoking (including e-cigarettes) either current or within 3 months before screening.

• Current or chronic liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP) >2x Upper Limit of Normal (ULN) and bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than (<) 35% at screening).

• Clinically significant abnormalities detected on ECG of either rhythm or conduction, a Corrected QT interval (QTc) >450 millisecond (msec) or QTc > 480msec for participants with a bundle branch block and/or a pacemaker who are actively ventricularly pacing during the screening ECG.

• Participants with pacemakers who are not pacing at the time of the screening ECG should have a non-paced QTc <450 msec.

Prior/Concomitant Therapy-

• Simultaneous use of pirfenidone and nintedanib at screening.

• Received systemic corticosteroids equivalent to prednisone >10 mg/day or equivalent within 2 weeks of screening period.

• Use of any of the following therapies within 4 weeks prior to screening and during the screening period or planned during the study:

• Immunomodulatory therapies, including but not limited to azathioprine, mycophenolate mofetil, methotrexate, tacrolimus, cyclophosphamide, imatinib, Tumour Necrosis Factor -Alpha (TNF- a) inhibitors.

• Medications that are under investigation for the treatment of IPF including inhaled treprostinil and Phosphodiesterase-4 (PDE-4) inhibitors. Symptomatic cough therapies are allowed.

• Current use of systemic strong and moderate inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4) (see prohibited medication section for further information) that cannot be safely discontinued or switched to an alternative agent at least 14 days before randomization.

• Current use of systemic CYP3A4 substrates that have a narrow therapeutic index that cannot be safely discontinued or switched to an alternative agent at least 14 days before randomization.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• GSK3915393
GSK3915393 will be administered.
• Placebo
Placebo will be administered.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Change from Baseline in Forced Vital Capacity (FVC) in milliliters (mL) at Week 26		Baseline and at Week 26
Secondary	Absolute Change from Baseline in Forced Vital Capacity (mL) at Weeks 4, 8, 12 and 18		Baseline and at Week 4, Week 8, Week 12 and Week 18
Secondary	Absolute Change from Baseline in Percent Predicted Forced Vital Capacity (%) at Weeks 4, 8, 12, 18 and 26		Baseline and at Week 4, Week 8, Week 12, Week 18 and Week 26
Secondary	Participants Achieving Relative Decline from Baseline in FVC (mL) Less than or Equal to (=) 5 Percent (%) at Week 26		Baseline and at Week 26
Secondary	Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to Week 26
Secondary	Number of Participants with Clinically Important Findings in Vital Signs		Baseline and Up to Week 26
Secondary	Number of Participants with Clinically Important Findings in Electrocardiogram (ECG)		Baseline and up to Week 26
Secondary	Number of Participants with Clinically Important Findings in Haematology		Baseline and up to Week 26
Secondary	Number of Participants with Clinically Important Findings in Hepatobiliary Parameters		Baseline and up to Week 26
Secondary	Number of Participants with Clinically Important Findings in Clinical Chemistry		Baseline and up to Week 26
Secondary	Maximum observed concentration (Cmax) of GSK3915393 in IPF Participants		At Week 2 (pre-dose, and 0.5, 1, 1.5, 2, 3 and 4 hour (h) post-dose)
Secondary	Area under the time-concentration curve (AUC) from Zero (pre-dose) to 4 hours (h) post-dose sample [0-4 h]) of GSK3915393		At Week 2 (pre-dose, and 0.5, 1, 1.5, 2, 3 and 4 hour (h) post-dose)
Secondary	Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC- inf) of GSK3915393		At Week 2 (pre-dose, and 0.5, 1, 1.5, 2, 3 and 4 hour (h) post-dose)