GSK3915393 Advanced Drug Monograph

GSK3915393 Medication Report

Name: GSK3915393 English Name: GSK3915393

Description: GSK3915393 is a novel, small molecule inhibitor of transglutaminase 2 (TG2) being developed by GlaxoSmithKline (GSK).

Mechanism of Action: GSK3915393 works by inhibiting the TG2 enzyme. In the context of celiac disease, TG2 modifies gluten, which then triggers an immune response. By blocking TG2, GSK3915393 aims to prevent this immune reaction to gluten. In idiopathic pulmonary fibrosis (IPF), the role of TG2 is also being investigated in the fibrotic process.

Current Development Status:

• Idiopathic Pulmonary Fibrosis (IPF): Currently in Phase II clinical trials to evaluate its efficacy and safety in reducing the decline in lung volume in participants with IPF.
• Celiac Disease: Development for celiac disease has been discontinued by GSK. Phase I studies have been completed to assess safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy participants and patients with celiac disease.

Route of Administration: GSK3915393 has been administered orally (capsules) and intravenously in clinical trials.

Clinical Trials: Several clinical trials have been conducted or are ongoing to evaluate GSK3915393:

• IPF Studies:
  • A Phase 2 study (TRANSFORM) to evaluate the efficacy and safety of GSK3915393 in participants with IPF (NCT06317285).
  • A Phase 2 study to evaluate the efficacy and safety of GSK3915393 compared to placebo in participants with IPF (NCT04604795).
• Celiac Disease Studies:
  • A Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of GSK3915393 in healthy participants and patients with celiac disease (IRAS ID: 1003407, EudraCT Number: 2020-003213-36). This study included assessments of single and repeat doses, the effect of food, and potential interactions with grapefruit juice and itraconazole (NCT04604795).
  • A Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of single doses of GSK3915393 in healthy participants of Chinese, Japanese, and European ancestry.

Potential Uses:

• Idiopathic Pulmonary Fibrosis (IPF): Investigational treatment aimed at slowing the progression of lung scarring.
• Celiac Disease: (Development discontinued) Previously investigated to reduce the immune response to gluten.

Safety and Tolerability: As GSK3915393 is still under clinical investigation, its complete safety and tolerability profile is not yet fully established. Clinical trials are ongoing to identify potential adverse events, changes in laboratory values, vital signs, and electrocardiogram (ECG) results associated with the drug.

Drug Interactions: One Phase 1 study evaluated the interaction of GSK3915393 with grapefruit juice and itraconazole. Another study is investigating the interaction between GSK3915393 and nintedanib in IPF patients.

Note: GSK3915393 is an investigational drug and is not currently approved for general use. The information provided here is based on publicly available clinical trial data and research findings and is subject to change as more data become available.