ToxicityPhase 1NCT04676711
A Study of GFH312 in Healthy Subjects
A Phase 1 study testing GFH312 in people with Toxicity and Healthy, run by GenFleet Therapeutics (Australia) Pty Ltd. at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- What is being tested?
- GFH312
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteAustralia
- Study dates
- 27 Apr 2021to 31 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- Healthy subjects fulfilling any of the following criteria are not eligible for inclusion in this study:
- 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.
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- 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.
- History of hypersensitivity to any of the study treatments or excipients (e.g., lactose monohydrate) or to drugs of similar chemical classes; and history of anaphylaxis or other significant allergy in the opinion of the Investigator.
- Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation.
- Plasma donation (>400 mL) within 14 days prior to first dosing.
- Use of any prescription drugs, herbal supplements (including Silybum marianum and Valeriana officinalis), within two weeks prior to initial dosing, and/or over-the- counter (OTC) medication, dietary supplements (vitamins included) within one weeks prior to initial dosing.
- Smokers of more than two per week. Urine cotinine levels will be measured during screening, and urine cotinine ≥ 500 ng/ml will exclude a subject.
- History of drug abuse or unhealthy alcohol use within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening.
- History of recreational cannabis use within four weeks prior to dosing, or evidence of such use as indicated by the laboratory assays conducted during screening.
- Participant is unwilling to refrain from strenuous exercise (including weightlifting) from 7 days prior to admission to the site until completion of the final Follow-up visit.
- With a plan to receive vaccination with a live vaccine within 4 weeks prior to the first dosing or within 4 weeks of the last dosing; With a plan to receive COVID-19 vaccination within 2 weeks prior to the first dosing or within 1 week of the last dosing.
- Exposure to any significantly immune suppressing drug (including experimental therapies as part of a clinical trial) within the 4 months prior to screening or 5 half-lives, whichever is longer.
- Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, or twice the duration of the biological effect of the investigational product, whichever is longer; or longer if required by local regulations.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- (Part Ⅱ only) Score 'yes' on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or 'yes' on any item of the Suicidal Behavior section, except for the 'Non-Suicidal Self-Injurious Behavior' (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years. Or history of drug abuse or mental disease.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A First-in-human, Randomized, Double-blinded, Placebo- Controlled, Two-part Study to Assess Safety/Tolerability and Pharmacokinetics of Single- and Multiple-ascending Doses and Food Effect of GFH312 in Healthy Subjects
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.
- Being tested
- GFH312, Placebo
- Keywords
- Safety, Tolerability, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GFH312Drug
Subjects are planned to be dosed in oral tablet, with single and multiple ascending doses
PlaceboDrug
Subjects are planned to be dosed in oral tablet, with single and multiple ascending doses
| Study group | Role | What they receive |
|---|---|---|
| GFH312 | Experimental | Not described Receives: Drug: GFH312 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety /Tolerability of GFH312 (adverse events)
Incidence of adverse events and serious adverse events
Measured: approximately 45 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2020
- Study start27 Apr 2021
- Primary completion23 May 2022
- Study completion31 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ToxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- GenFleet Therapeutics (Australia) Pty Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04676711
- Sponsor's protocol ID
- GFH312X3101
- Status last verified
- May 2023
- First submitted
- 15 Dec 2020
- Last updated
- 15 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-in-human, Randomized, Double-blinded, Placebo- Controlled, Two-part Study to Assess Safety/Tolerability and Pharmacokinetics of Single- and Multiple-ascending Doses and Food Effect of GFH312 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04676711
- Acronym / sponsor ID
- GFH312X3101
- Keywords
- Safety, Tolerability, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- GenFleet Therapeutics (Australia) Pty Ltd.Industry (pharma, biotech, devices)
- Study start
- 27 Apr 2021 (actual)
- Primary completion
- 23 May 2022 (actual)
- Study completion
- 31 Oct 2022 (actual)
- First posted
- 21 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| GFH312 | Experimental | Drug: GFH312 |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (29 listed)
- Healthy subjects fulfilling any of the following criteria are not eligible for inclusion in this study:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GFH312Subjects are planned to be dosed in oral tablet, with single and multiple ascending doses | Drug | GFH312 |
| PlaceboSubjects are planned to be dosed in oral tablet, with single and multiple ascending doses | Drug | Placebo |
Primary outcome
Safety /Tolerability of GFH312 (adverse events)
Time frame: approximately 45 days
Incidence of adverse events and serious adverse events
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GFH312 in people with Toxicity and Healthy, run by GenFleet Therapeutics (Australia) Pty Ltd. at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety /Tolerability of GFH312 (adverse events) (time frame: approximately 45 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2023.