NCT04676711

A Study of GFH312 in Healthy Subjects

Completed Phase 1 Last updated 15 May 2023

What this trial tests

Phase 1 trial testing GFH312 in Toxicity in 76 participants. Completed in 31 October 2022.

Timeline

27 April 2021

Primary endpoint
23 May 2022

31 October 2022

Quick facts

Lead sponsor	GenFleet Therapeutics (Australia) Pty Ltd.
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	76
Start date	27 April 2021
Primary completion	23 May 2022
Estimated completion	31 October 2022
Sites	1 location across Australia

Drugs / interventions tested

• GFH312 — full drug profile →
• Placebo

Conditions studied

• Toxicity — all drugs for Toxicity →
• Healthy — all drugs for Healthy →

Sponsor

GenFleet Therapeutics (Australia) Pty Ltd.

Who can join

Adults 18 to 55, any sex, with Toxicity or Healthy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

GFH312 is a small molecule inhibitor of receptor-interacting serine/threonine protein-1(RIP1) kinase, a key regulator of the TNF-α downstream. RIPK1 can regulate the NF- κB signaling and necroptosis, a type of cell death which can trigger immune response and enhance inflammation. As such, GFH312 represents a novel, selective mechanism for the treatment of inflammatory conditions.

This study is the first administration of GFH312 to humans. The purpose of the study is to evaluate the safety/tolerability and pharmacokinetics in healthy subjects. The intention of this study is to provide confidence in the safety of the molecule to inform progression to further proof-of-concept studies. The dose range proposed in this study is based on a low starting dose escalating to supra-therapeutic doses.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. The role of necroptosis in disease and treatment.
   Liu X, Xie X, Ren Y, Shao Z, et al · · 2021 · cited 75× · PMID 34977874 · DOI 10.1002/mco2.108
2. Generative deep learning enables the discovery of a potent and selective RIPK1 inhibitor.
   Li Y, Zhang L, Wang Y, Zou J, et al · · 2022 · cited 67× · PMID 36371441 · DOI 10.1038/s41467-022-34692-w
3. From (Tool)Bench to Bedside: The Potential of Necroptosis Inhibitors.
   Gardner CR, Davies KA, Zhang Y, Brzozowski M, et al · · 2023 · cited 45× · PMID 36781172 · DOI 10.1021/acs.jmedchem.2c01621
4. Regulation of RIPK1 Phosphorylation: Implications for Inflammation, Cell Death, and Therapeutic Interventions.
   Du J, Wang Z. · · 2024 · cited 16× · PMID 39062098 · DOI 10.3390/biomedicines12071525
5. A phase I randomized, double-blinded, placebo-controlled study assessing the safety and pharmacokinetics of RIPK1 inhibitor GFH312 in healthy subjects.
   Lickliter J, Wang S, Zhang W, Zhu H, et al · · 2023 · cited 16× · PMID 37345561 · DOI 10.1111/cts.13580
6. RIPK1 signaling pathways: implications for autoimmune and neuroinflammatory diseases.
   Pajulas A, Sims JT, Hanson EP, Vendel AC. · · 2025 · cited 1× · PMID 41019071 · DOI 10.3389/fimmu.2025.1642593
7. RIPK 1 in Alzheimer's Disease: Research Progress Integrating Pathogenesis on Necroptosis-Related Neuroinflammation, and Potential Therapeutic Strategies.
   Toklucu ES, Shen S, Wang C, Zhang C. · · 2026 · PMID 42193479 · DOI 10.3390/biomedicines14051155