DF-003 Safety and Tolerability Study in Healthy Subjects

Overseen By Jeysen Yogaratnam, MB.BCh, MRCSed, PhD, MBA

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Zhejiang Yao Yuan Biotechnology Ltd. (also known as Drug Farm)

Must not be taking: Systemic contraceptives, Hormone therapy

Disqualifiers: Pregnancy, Renal dysfunction, Cardiovascular, others

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, DF-003, to assess its safety and tolerability in healthy individuals. Researchers are studying DF-003 for its potential to treat chronic kidney disease by reducing inflammation and kidney scarring. The trial consists of two parts: one where participants take a single dose and another with multiple doses. Healthy individuals who do not smoke, have no significant health issues, and are not on regular medication might be suitable for this study. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

Yes, participants must stop taking any prescription drugs 28 days before the study and over-the-counter medications 7 days before the study starts.

Is there any evidence suggesting that DF-003 is likely to be safe for humans?

Research has shown that DF-003 was tested safely in earlier studies, with no serious side effects reported. Some participants experienced side effects, but none were serious. This indicates that DF-003 was generally well-tolerated at all tested doses. These findings suggest that DF-003 is generally safe for humans, even at varying dose levels. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about DF-003 because it offers a potentially new approach to treating conditions that currently rely on standard medications. Unlike existing treatments which often involve complex mechanisms and slower onset, DF-003 is being studied for its unique dosing strategy, which includes both single and multiple ascending doses. This flexibility could lead to more personalized treatment options, allowing doses to be tailored based on individual needs. Additionally, DF-003's oral administration makes it easy to take, possibly improving patient adherence compared to more cumbersome alternatives.

What evidence suggests that DF-003 might be an effective treatment for chronic kidney disease?

Research has shown that DF-003 is a powerful compound targeting ALPK1, a key player in immune responses and inflammation. Early animal studies demonstrated that DF-003 reduces kidney scarring, suggesting potential benefits for chronic kidney disease. In this trial, participants will receive DF-003 in either single or multiple ascending doses to assess its safety and tolerability. DF-003 has also been tested in other conditions and proved safe in healthy volunteers. These early findings are promising, but further research is needed to confirm its effectiveness in people. ^{2 3 6 7 8}

Who Is on the Research Team?

Javid Ghandehari, MD

Principal Investigator

Interventional Pain Management Physician Anesthesiologist, Altasciences

Are You a Good Fit for This Trial?

Healthy adults, aged 18-55, who are non-smokers or have quit smoking for at least 3 months. Women must be postmenopausal or surgically sterile; men should agree not to donate sperm and use contraception if necessary. Participants must have a stable heart rate and normal ECG readings, with no significant medical history that could affect the study.

Inclusion Criteria

I am a healthy adult.

Provision of signed and dated informed consent form (ICF)

Meets criteria for ECG parameters

Exclusion Criteria

Presence of clinically significant ECG abnormalities

Positive test results for alcohol, drugs of abuse, or infectious diseases

I or my family have a history of skin diseases or immune disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Single Ascending Dose (SAD) Phase

Participants receive a single oral dose of DF-003 or placebo to evaluate safety and pharmacokinetics

1 day

1 visit (in-person)

Multiple Ascending Dose (MAD) Phase

Participants receive multiple doses of DF-003 or placebo to evaluate safety and pharmacokinetics over 14 days

2 weeks

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DF-003

Trial Overview The trial is testing DF-003's safety and how it's processed by the body when taken orally in single/multiple doses by healthy people. It will also look into whether food affects its absorption. The drug targets an enzyme involved in immunity/inflammation and may help treat chronic kidney disease.

How Is the Trial Designed?

Group I: DF-003 (Single Ascending Dose, Part 1) Experimental Treatment 1 Intervention

Participants will receive a single oral dose of 3 mg DF-003 (1 mg x 3).

Group II: DF-003 (Multiple Ascending Doses, Part 2) Experimental Treatment 1 Intervention

Participants will receive DF-003 once daily by oral administration for 14 days. The specific doses given will be based on data collected in Part 1 of the study. This part of the study may include 1 mg, 5 mg, or 25 mg capsules.

Group III: Placebo (Single Ascending Dose, Part 1) Placebo Group 1 Intervention

Visually matching 0 mg DF-003 capsules.

Group IV: Placebo (Multiple Ascending Doses, Part 2) Placebo Group 1 Intervention

Visually matching 0 mg DF-003 capsules.

Who Is Running the Clinical Trial?

Zhejiang Yao Yuan Biotechnology Ltd. (also known as Drug Farm)

Lead Sponsor

Trials

1

Recruited

100+

Shanghai Yao Yuan Biotechnology Ltd. (also known as Drug Farm)

Lead Sponsor

Trials

2

Recruited

110+

Published Research Related to This Trial

The benchmark dose (BMD) modeling approach provides more detailed insights into dose-response relationships in drug development compared to the traditional no-observed-adverse-effect-level (NOAEL) method, allowing for better hazard characterization.

Using BMD modeling can reduce the need for animal testing by yielding more information from fewer animals and lower doses, making it a promising alternative or complement to the NOAEL approach in assessing potential drug toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benchmark dose-response analyses for multiple endpoints in drug safety evaluation. Vieira Silva, A., Ringblom, J., Moldeus, P., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06395285

Study Details | NCT06395285 | Evaluating the Safety and ... The purpose of this study is to evaluate the safety and tolerability of DF-003 in retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05997641/evaluating-the-safety-tolerability-and-pharmacokinetics-of-df-003-in-healthy-subjects?mp=msfocus&page=1&state=CA&city=Cypress

Evaluating the Safety, Tolerability, and Pharmacokinetics of ... The choice of using healthy subjects is standard in establishing the preliminary safety and PK profile of a drug. DF-003 is a potent small ...

3. firstwordpharma.com firstwordpharma.com/story/5967277

Drug Farm Reports Data on Safety and Pharmacokinetics ... This randomized, placebo-controlled, double-blinded study evaluated the safety, tolerability and pharmacokinetics of DF-003 in forty-eight healthy volunteers.

4. trialx.com trialx.com/clinical-trials/listings/296759/evaluating-the-safety-and-tolerability-of-orally-administered-df-003-in-rosah-syndrome-patients/

Clinical Research Trial Listing ( ROSAH ) ( NCT06395285 ) The purpose of this study is to evaluate the safety and tolerability of DF-003 in retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis ...

5. trial.medpath.com trial.medpath.com/news/f796a678ff57e4cb/drug-farm-s-df-003-shows-promising-safety-profile-in-phase-1-trial-for-rare-rosah-syndrome

Drug Farm's DF-003 Shows Promising Safety Profile in Phase ... Drug Farm reported positive Phase 1 results for DF-003, a first-in-class ALPK1 inhibitor targeting ROSAH syndrome, showing excellent safety with ...

6. businesswire.com businesswire.com/news/home/20250529149642/en/Drug-Farm-Reports-Data-on-Safety-and-Pharmacokinetics-from-Phase-1-First-in-Human-Trial-of-DF-003-in-Healthy-Volunteers

Drug Farm Reports Data on Safety and Pharmacokinetics ... Safety: DF-003 was safe at all doses tested with no serious adverse events described. Rates of treatment emergent adverse events (TEAEs) were ...

7. biospace.com biospace.com/drug-farm-announces-ind-clearance-by-u-s-fda-enabling-phase-1b-initiation-for-alpk1-selective-kinase-inhibitor-df-003-in-rosah-syndrome-patients

Drug Farm Announces IND Clearance by U.S. FDA ... Furthermore, DF-003 has completed Phase 1 evaluation in healthy subjects with safety and pharmacokinetics supporting a once-a-day oral ...

8. synapse.patsnap.com synapse.patsnap.com/article/drug-farm-gets-fda-ind-clearance-to-start-phase-1b-for-df-003-in-rosah-syndrome

Drug Farm Gets FDA IND Clearance to Start Phase 1b for ... Moreover, Phase 1 trials involving healthy subjects have already been completed, indicating that the drug is safe and supports a once-daily oral ...