GSK3915393 for Pulmonary Fibrosis

No longer recruiting at 71 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must be taking: Antifibrotics

Must not be taking: Immunomodulatory, Corticosteroids, CYP3A4 inducers

Disqualifiers: Interstitial lung disease, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, GSK3915393, to determine its potential benefits for people with Idiopathic Pulmonary Fibrosis (IPF), a lung disease that causes breathing difficulties due to lung scarring. Researchers aim to assess the safety and effectiveness of this treatment for those living with IPF. The trial includes different groups, with some participants receiving the new medicine and others receiving a placebo (a pill with no active ingredients). Suitable candidates have been diagnosed with IPF within the last five years and have experienced breathing difficulties due to lung scarring. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that if you are taking antifibrotic medications like nintedanib or pirfenidone, you must be on a stable dose for at least 12 weeks before screening. If you are not taking these, you must have stopped them at least 4 weeks before screening. Some other medications, like certain immunomodulatory therapies and specific enzyme inhibitors, must be stopped at least 14 days before joining the trial.

Is there any evidence suggesting that GSK3915393 is likely to be safe for humans?

Research shows that GSK3915393 is undergoing its first test in people with Idiopathic Pulmonary Fibrosis (IPF). Limited information exists on how well people tolerate it or what side effects may occur. This trial aims to assess its safety. As an early-stage trial, researchers closely monitor the safety of GSK3915393. Participants will help researchers identify any risks or side effects, enabling them to determine its safety for people with IPF. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary fibrosis?

Most treatments for pulmonary fibrosis, like nintedanib and pirfenidone, work by slowing the progression of the disease with anti-fibrotic properties. However, GSK3915393 stands out because it targets a different pathway involved in the disease process. Researchers are excited about this treatment as it promises to address the underlying mechanisms of fibrosis potentially more effectively. This unique approach could offer an alternative for patients who do not respond well to existing treatments, providing hope for improved management of the condition.

What evidence suggests that GSK3915393 might be an effective treatment for pulmonary fibrosis?

Research has shown that GSK3915393 is being tested as a new treatment for idiopathic pulmonary fibrosis (IPF), a serious lung disease that causes scarring and makes breathing difficult. Early results suggest this medicine might slow lung damage in people with IPF. In this trial, participants will receive either GSK3915393 or a placebo. A study of 210 IPF patients found that those with a specific genetic marker experienced better results and lower death rates when taking GSK3915393. Although human studies have provided limited information, this new treatment is being assessed for its potential to improve lung function and overall quality of life in IPF patients. ^{1 2 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for adults with Idiopathic Pulmonary Fibrosis (IPF), diagnosed within the last 5 years, who have a certain level of lung function and are either on stable antifibrotic treatment or not taking it. They must be able to consent and meet specific weight and body mass index criteria.

Inclusion Criteria

My latest chest scan shows signs of a specific lung condition.

My lung function is at least 45% of what is expected for someone healthy.

I have been on a stable dose of nintedanib or pirfenidone for at least 12 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either GSK3915393 or placebo to evaluate efficacy and safety in IPF

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GSK3915393

Trial Overview The study tests GSK3915393's safety and effectiveness against IPF compared to a placebo. Participants will randomly receive either the new medicine or an inactive substance to see if there's an improvement in their lung condition.

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 1 Intervention

Participants will receive placebo.

Group II: GSK3915393 Experimental Treatment 1 Intervention

Participants will receive GSK3915393

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

Pirfenidone effectively reduces lung fibrosis in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) by inhibiting the hedgehog (Hh) signaling pathway, as demonstrated in a study involving 25 patients and 10 healthy controls.

The treatment also upregulates the protein Sufu in lung fibroblasts and inhibits the phosphorylation of GSK-3β, suggesting a dual mechanism of action that could be beneficial for other lung diseases driven by Hh signaling, such as idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-fibrotic effects of pirfenidone by interference with the hedgehog signalling pathway in patients with systemic sclerosis-associated interstitial lung disease. Xiao, H., Zhang, GF., Liao, XP., et al.[2020]

A new orally active drug that selectively inhibits the kinase activity of ALK5, a receptor for TGF-beta, shows promise in treating pulmonary fibrosis by blocking both the initiation and progression of the disease in a rat model.

The drug was effective not only when given at the start of fibrosis development but also when administered to rats with established fibrosis, suggesting it could be a potential therapeutic option for patients with idiopathic pulmonary fibrosis (IPF).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progressive transforming growth factor beta1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor. Bonniaud, P., Margetts, PJ., Kolb, M., et al.[2022]

In a study of 210 idiopathic pulmonary fibrosis (IPF) patients, those with the DSP rs2076295*G allele showed significantly lower mortality and better outcomes with nintedanib treatment, indicating a potential genetic marker for treatment efficacy.

Patients with the TT genotype of DSP rs2076295 benefited more from pirfenidone, suggesting that genetic profiling could help tailor antifibrotic therapy in IPF, although the MUC5B rs35705950*T allele did not influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study. Doubkova, M., Kriegova, E., Littnerova, S., et al.[2022]

The study identified that the GSK-3β signaling pathway plays a crucial role in the differentiation of fibroblasts into myofibroblasts, which contributes to the progression of idiopathic pulmonary fibrosis (IPF).

The novel inhibitor 9-ING-41 effectively blocked myofibroblast differentiation and improved lung function in mouse models of pulmonary fibrosis, suggesting its potential as a therapeutic option for patients with IPF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycogen Synthase Kinase-3β Inhibition with 9-ING-41 Attenuates the Progression of Pulmonary Fibrosis. Jeffers, A., Qin, W., Owens, S., et al.[2021]

The study identifies a critical pathway involving the proteins TRIB3, GSK-3β, A20, and C/EBPβ that promotes the development of pulmonary fibrosis (PF) in alveolar macrophages, highlighting a potential target for therapeutic intervention.

Knocking down TRIB3 or disrupting its interaction with GSK-3β effectively treated PF, suggesting that targeting this pathway could lead to new treatment strategies for this chronic lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TRIB3‒GSK-3β interaction promotes lung fibrosis and serves as a potential therapeutic target. Liu, S., Lv, X., Wei, X., et al.[2021]

Chronic lung injury leads to the inactivation of the A20 enzyme, resulting in the accumulation of the C/EBPβ transcription factor in alveolar macrophages, which promotes the development of pulmonary fibrosis (PF).

Restoring A20 activity through pharmacological means or ectopic expression can enhance the degradation of C/EBPβ and shows strong therapeutic potential against experimental PF, suggesting that targeting the GSK-3β-A20-C/EBPβ pathway may be an effective strategy for treating PF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Degradation of the Transcription Factor C/EBPβ Reduces Lung Fibrosis by Restoring Activity of the Ubiquitin-Editing Enzyme A20 in Macrophages. Liu, SS., Lv, XX., Liu, C., et al.[2019]

GSK3008348, an inhaled drug targeting the αvβ6 integrin, was found to be safe and well tolerated in a phase 1 trial with 29 healthy participants, with no serious adverse events reported.

The pharmacokinetic profile showed that maximum plasma concentrations were reached within 30 minutes, and the drug's exposure was dose proportional at doses up to 3000 mcg, supporting its potential as a treatment for idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and pharmacokinetics of GSK3008348, a novel integrin αvβ6 inhibitor, in healthy participants. Maden, CH., Fairman, D., Chalker, M., et al.[2018]

In a study of 92 patients with idiopathic pulmonary fibrosis (IPF) receiving pirfenidone, the drug showed an acceptable safety profile, with skin-related (25%) and gastrointestinal (17.5%) adverse events being the most common, leading to discontinuation in 22.5% of cases.

Despite some patients experiencing significant improvements in lung function, the overall decline in lung function (%FVC and %DLCO) was noted over 36 months, highlighting the need for further research through prospective observational registries to better understand pirfenidone's long-term efficacy in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal "Real-World" Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece. Tzouvelekis, A., Karampitsakos, T., Ntolios, P., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06317285

NCT06317285 | A Study to Evaluate the Efficacy and ... Idiopathic Pulmonary Fibrosis is a chronic lung disease which causes scarring of the lungs and difficulty in breathing. GSK3915393 is a new medicine, ...

2. actionpf.org actionpf.org/research-study/a-study-looking-at-the-impact-of-a-new-drug-gsk3915393-on-the-lung-function-for-people-with-idiopathic-pulmonary-fibrosis-ipf

A study looking at the impact of a new drug, GSK3915393, ... In this study, researchers aim to evaluate the safety and effectiveness of GSK3915393 in people with IPF. They will test to see if GSK3915393 can help slow down ...

3. pulmonaryfibrosis.org pulmonaryfibrosis.org/patients-caregivers/medical-and-support-resources/clinical-trials-education-center/pipeline/drug/idiopathic-pulmonary-fibrosis/gsk3915393

GSK3915393 The study will assess the safety and effectiveness of GSK3915393 in participants with IPF.

4. mayo.edu mayo.edu/research/clinical-trials/cls-20569429

Clinical Trials About this study. The purpose of this study is to evaluate the efficacy of GSK3915393 administered twice daily, compared with placebo on ...

5. withpower.com withpower.com/trial/phase-2-pulmonary-fibrosis-3-2024-35d1e

GSK3915393 for Pulmonary Fibrosis · Info for Participants In a study of 210 idiopathic pulmonary fibrosis (IPF) patients, those with the DSP rs2076295*G allele showed significantly lower mortality and better outcomes ...

6. clinicaltrials.eu clinicaltrials.eu/inn/gsk3915393/

GSK3915393: A New Drug for Idiopathic Pulmonary Fibrosis The main goal of the clinical trials is to evaluate the safety, tolerability, and effectiveness of GSK3915393 in patients with Idiopathic Pulmonary Fibrosis.

7. orpha.net orpha.net/en/research-trials/clinical-trial/696473

TRANSFORM-IPF: A Phase 2, Randomized, Double-Blind, ... Orphanet produces its data according to published procedures. Read ... Safety of GSK3915393 in Participants With Idiopathic Pulmonary Fibrosis (IPF) - PL.

8. trial.medpath.com trial.medpath.com/drug/report/407399d8359cce3b

GSK3915393 | Advanced Drug Monograph - MedPath Comprehensive analysis about GSK3915393, including its mechanisms, clinical uses, and therapeutic considerations.