A Study of GFH312 in Healthy Subjects

NCT04676711 | Completed Phase 1

• 1 other identifier: GFH312X3101
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Toxicity; Healthy

Keywords

Safety; Tolerability; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Safety /Tolerability of GFH312 (adverse events)

  Incidence of adverse events and serious adverse events

  approximately 45 days

Study Arms (2)

GFH312

EXPERIMENTAL

Drug: GFH312

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

GFH312 DRUG

Subjects are planned to be dosed in oral tablet, with single and multiple ascending doses

GFH312

Placebo DRUG

Subjects are planned to be dosed in oral tablet, with single and multiple ascending doses

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent must be obtained before any assessment is performed.
• Healthy male and female subjects age 18 to 55 years of age included.
• Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18-32 kg/m2 inclusive.
• At screening, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three minutes, and again (when required) after three minutes in the standing position. Sitting vital signs should be within the normal ranges.
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant must use highly effective methods of contraception during intercourse while taking drug and for 30 days after stopping study medication; and sexually active males must use a condom, during intercourse while taking drug and for 30 days after stopping study medication.
• Able to communicate well with the investigator, to understand and comply with the requirements of the study.

You may not qualify if:

• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
• Hemoglobin levels below the lower limit of normal (LLN) as set by the laboratory.
• An elevated C-reactive protein (CRP) outside of the normal reference range and has clinical significance, or above 10 mg/L.
• A positive anti-nuclear antibody (ANA) above 1:160 titer.
• A positive Tuberculosis test.
• A history of clinically significant ECG abnormalities, or any abnormalities defined in protocol.
• History of immunodeficiency diseases, including a positive test for HIV antibody.
• Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).
• Infections requiring parenteral antibiotics within the 6 months prior to Screening.
• History of any venous thromboembolism, TIA, intracranial hemorrhage, neoplasm, arteriovenous malformation, vasculitis, bleeding disorder, coagulation disorders or screening blood tests that indicate altered coagulability (platelet count, APTT, PT, etc.).
• History of significant cardiovascular, respiratory, renal, neurological disease.
• Significant illness which has not resolved within two (2) weeks prior to initial dosing.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Recent (within the last three years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.).
• Known family history or known presence of long QT syndrome, or concomitant use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of study.

Sponsors & Collaborators

• GenFleet Therapeutics (Australia) Pty Ltd.: lead

Study Sites (1)

Nucleus Network Pty Ltd

Melbourne, Victoria, 3004, Australia

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study drug: GFH312 and placebo In part Ia, subjects will be randomized and dosed in different cohorts in single dose. In part Ib, one of the cohorts will selected as food effect cohort with washout period of part Ia. In part II, subjects will be randomized and dosed in different cohorts in multiple doses.

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 21, 2020
• Study Start: April 27, 2021
• Primary Completion: May 23, 2022
• Study Completion: October 31, 2022
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)