Clinical trial NCT06317285: A Study to Evaluate the Efficacy and Safety of GSK3915393 in Participants With Idiopathic Pulmonary Fibrosis (IPF)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: GSK3915393
Idiopathic Pulmonary Fibrosis
Efficacy
Safety
Forced vital capacity
Tolerability
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-03-19
Enrollment: 150
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: 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.


Eligibility criteria: 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- α) 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.

Primary outcomes:
measure: Absolute Change from Baseline in Forced Vital Capacity (FVC) in milliliters (mL) at Week 26
timeFrame: Baseline and at Week 26
Secondary outcomes:
measure: Absolute Change from Baseline in Forced Vital Capacity (mL) at Weeks 4, 8, 12 and 18
timeFrame: Baseline and at Week 4, Week 8, Week 12 and Week 18
measure: Absolute Change from Baseline in Percent Predicted Forced Vital Capacity (%) at Weeks 4, 8, 12, 18 and 26
timeFrame: Baseline and at Week 4, Week 8, Week 12, Week 18 and Week 26
measure: Participants Achieving Relative Decline from Baseline in FVC (mL) Less than or Equal to (≤) 5 Percent (%) at Week 26
timeFrame: Baseline and at Week 26
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 26
measure: Number of Participants with Clinically Important Findings in Vital Signs
timeFrame: Baseline and Up to Week 26
measure: Number of Participants with Clinically Important Findings in Electrocardiogram (ECG)
timeFrame: Baseline and up to Week 26
measure: Number of Participants with Clinically Important Findings in Haematology
timeFrame: Baseline and up to Week 26
measure: Number of Participants with Clinically Important Findings in Hepatobiliary Parameters
timeFrame: Baseline and up to Week 26
measure: Number of Participants with Clinically Important Findings in Clinical Chemistry
timeFrame: Baseline and up to Week 26
measure: Maximum observed concentration (Cmax) of GSK3915393 in IPF Participants
timeFrame: At Week 2 (pre-dose, and 0.5, 1, 1.5, 2, 3 and 4 hour (h) post-dose)
measure: Area under the time-concentration curve (AUC) from Zero (pre-dose) to 4 hours (h) post-dose sample [0-4 h]) of GSK3915393
timeFrame: At Week 2 (pre-dose, and 0.5, 1, 1.5, 2, 3 and 4 hour (h) post-dose)
measure: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC- inf) of GSK3915393
timeFrame: At Week 2 (pre-dose, and 0.5, 1, 1.5, 2, 3 and 4 hour (h) post-dose)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Saint Petersburg
country: United States
facility: GSK Investigational Site
state: Florida
city: Ann Arbor
country: United States
facility: GSK Investigational Site
state: Michigan
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Wilmington
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Cypress
country: United States
facility: GSK Investigational Site
state: Texas
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Florida
country: Argentina
facility: GSK Investigational Site
city: La Plata
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Saint John's
country: Canada
facility: GSK Investigational Site
state: Newfoundland and Labrador
city: Ajax
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Trois RiviEres
country: Canada
facility: GSK Investigational Site
state: Quebec
city: La Tronche
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Pessac cedex
country: France
facility: GSK Investigational Site
city: Rennes
country: France
facility: GSK Investigational Site
city: Rouen Cedex
country: France
facility: GSK Investigational Site
city: Toulouse cedex 9
country: France
facility: GSK Investigational Site
city: Essen
country: Germany
facility: GSK Investigational Site
city: Hannover
country: Germany
facility: GSK Investigational Site
city: Heidelberg
country: Germany
facility: GSK Investigational Site
city: Immenhausen
country: Germany
facility: GSK Investigational Site
city: Wuppertal
country: Germany
facility: GSK Investigational Site
city: Catania
country: Italy
facility: GSK Investigational Site
city: Monza MB
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Padova
country: Italy
facility: GSK Investigational Site
city: Perugia
country: Italy
facility: GSK Investigational Site
city: Pisa
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Sassari
country: Italy
facility: GSK Investigational Site
city: Torrette AN
country: Italy
facility: GSK Investigational Site
city: Eindhoven
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Oviedo
country: Spain
facility: GSK Investigational Site
city: Pozuelo De AlarcOn Madr
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
city: Leeds West Yorkshire
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: