Evaluating the Safety, Tolerability, and Pharmacokinetics of DF-003 in Healthy Subjects

NCT05997641 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DF-003-1001
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetics (PK; drug metabolism) of DF-003 after oral administration of single and multiple ascending doses in healthy subjects. 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 molecule inhibitor of alpha-kinase 1 (ALPK1), which plays an important role in immunity and inflammation. DF-003 can inhibit the immune inflammatory response and has been shown to reduce renal fibrosis in preclinical models. Thus, this study aims to determine the role of DF-003 in the treatment of chronic kidney disease. This study will include 2 parts. Part 1 is a single ascending dose (SAD) phase with an optional food effect (FE) assessment, while Part 2 is a multiple ascending dose (MAD) phase. Part 1 - SAD Phase with optional FE assessment will include approximately 64 subjects (up to 8 cohorts of 8 subjects each) and Part 2 - MAD Phase will include approximately 32 subjects (up to 4 cohorts of 8 subjects each). Therefore, up to 96 subjects will be included in the study. Study participants will be screened approximately 42 days within the first scheduled administration of study medication. Screening data will be reviewed to determine subject eligibility. In Part 1, subjects will be randomly assigned to receive a single oral dose of DF-003 (3 x 1 milligram capsules) or matching placebo. The doses to be evaluated in Part 2 will be determined based on review of the available safety and PK data from Part 1. Subjects will be monitored for adverse events (AEs) and data will be collected for physical examination, eye examination, vital signs, 12-lead electrocardiogram (ECG), Holter monitoring, and clinical laboratory findings at various timepoints throughout the study.

Conditions

Healthy; Safety and Tolerability

Keywords

DF-003

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events (AEs)

  Safety and Tolerability

  Up to 83 days

• Incidence of Serious Adverse Events (SAEs)

  Safety and Tolerability

  Up to 83 days

Secondary Outcomes (15)

• Maximum plasma concentration (Cmax) for DF-003

  Up to 83 days

• Time to maximum plasma concentration (tmax) for DF-003

  Up to 83 days

• Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUC(0-t)) for DF-003

  Up to 83 days

• Area under the plasma concentration-time curve from zero to infinity ((AUC(0-∞)) for DF-003

  Up to 83 days

• Terminal half-life (t½) for DF-003

  Up to 83 days

Study Arms (4)

DF-003 (Single Ascending Dose, Part 1)

EXPERIMENTAL

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

Drug: DF-003

Placebo (Single Ascending Dose, Part 1)

PLACEBO COMPARATOR

Visually matching 0 mg DF-003 capsules.

Drug: Placebo

DF-003 (Multiple Ascending Doses, Part 2)

EXPERIMENTAL

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.

Drug: DF-003

Placebo (Multiple Ascending Doses, Part 2)

PLACEBO COMPARATOR

Visually matching 0 mg DF-003 capsules.

Drug: Placebo

Interventions

DF-003 DRUG

Oral administration by capsules (1 mg, 5 mg, or 25 mg).

DF-003 (Multiple Ascending Doses, Part 2); DF-003 (Single Ascending Dose, Part 1)

Placebo DRUG

Visually matching 0 mg DF-003 capsules.

Placebo (Multiple Ascending Doses, Part 2); Placebo (Single Ascending Dose, Part 1)

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form (ICF).
• Ability to understand and stated willingness to comply with all study procedures and availability for the duration of the study, and likeliness to complete the study as planned, per the Investigator's opinion.
• Healthy adult male or female.
• If male, meets one of the following criteria:
• Is able to procreate and agrees not to donate sperm from the first study drug administration to at least 90 days after the last study drug administration in addition to:
• Having a female partner who is postmenopausal, surgically sterile, or otherwise incapable of becoming pregnant, OR
• Having a female partner who is a woman of childbearing potential and agrees to use a highly effective method of contraception from the first study drug administration to at least 90 days after the last study drug administration, OR
• Is unable to procreate; defined as surgically sterile (ie, has undergone a vasectomy at least 180 days prior to the first study drug administration).
• If female, meets one of the following criteria:
• Physiological postmenopausal status, defined as the following:
• Amenorrhea for at least 12 months prior to the first study drug administration (without an alternative medical condition); AND
• Follicle stimulating hormone (FSH) levels ≥40 mIU/mL at Screening;
• In the absence of 12 months of amenorrhea, 2 FSH measurements at least 3 months apart and in the postmenopausal range must be documented.
• Surgical postmenopausal status, defined as having had a bilateral oophorectomy or bilateral salpingo-oophorectomy with FSH levels ≥ 40 mIU/mL at Screening.
• Aged at least 18 years but not older than 55 years at the time of Screening.

You may not qualify if:

• Female who is lactating.
• Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration
• Female using the following systemic contraceptives: oral, patch or vaginal ring, in the 28 days prior to the first study drug administration.
• Female using hormone replacement therapy in the 28 days prior to the first study drug administration.
• Female using the following systemic contraceptives: injections or implant, or hormone-releasing intrauterine device in the 13 weeks prior to the first study drug administration.
• History of significant hypersensitivity to products related to DF-003 (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
• Presence or history of significant gastrointestinal, liver or kidney disease, or surgery (with the exception of cholecystectomy and appendectomy) that may affect drug bioavailability.
• History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, rheumatologic, neoplastic, metabolic, or dermatologic disease.
• Presence of clinically significant ECG abnormalities at the Screening visit, as defined by medical judgment.
• Use of contact lenses or eyeglasses.
• Presence of clinically significant visual acuity or slit-lamp biomicroscopy abnormalities at the Screening visit, as defined by medical judgement.
• History or family history of chronic inflammatory skin disease (eg, psoriasis, atopic dermatitis, drug-related rash, or chronic urticaria), or immune or autoimmune related disorders, diseases, or syndromes.
• Major surgery (eg, requiring general anesthesia) within 12 weeks before Screening, during the study, or within 12 weeks after the last dose of study drug. NOTE: Subjects with planned surgical procedures to be conducted under local anesthesia may participate.
• Presence of renal dysfunction at Screening (eg, estimated glomerular filtration rate \< 90 mL/min/1.73 m\^2 calculated by the Chronic Kidney Disease Epidemiology Collaboration formula).
• Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic).

Sponsors & Collaborators

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

Study Sites (1)

Altasciences Clinical Los Angeles, Inc

Cypress, California, 90630, United States

Location

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Study Officials

• Javid Ghandehari, MD

  Interventional Pain Management Physician Anesthesiologist, Altasciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Each enrolled participant will be assigned a randomization code generated with a computer program. Once generated, the randomization code will be final and will not be modified. The randomization code will not be available to the personnel of the bioanalytical facility until the bioanalytical phase of the study has been completed. The treatment assignment will not be known by the study participants. Furthermore, the randomization code will not be available to the physician and clinical staff involved in the collection, monitoring, revision, or evaluation of adverse events, as well as clinical staff who could have an impact on the outcome of the study. The preparation and/or administration of the drug products will be done by designated personnel that are not directly involved in the clinical aspects of the trial.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will include 2 parts: 1) Single ascending dose phase with optional food effect (FE) assessment, and 2) multiple ascending dose phase.

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 18, 2023
• Study Start: September 15, 2023
• Primary Completion: March 23, 2024
• Study Completion: January 1, 2025
• Last Updated: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)