A First-in-Human SAD/MAD Study to Evaluate Safety, Tolerability and PK of ENC0653 Ointment in Healthy Adult Subjects

Official title

A Phase 1 Randomized, Double-Blind, Single-Center, Placebo-Controlled Single Ascending Dose and Multiple Ascending Dose (SAD/MAD) Study by Topical Dermal Administration to Evaluate the Safety, Tolerability, and Pharmacokinetics of ENC0653 Ointment in Healthy Adult Subjects

Overview

This is a FIH, randomized, double-blind, single-center, placebo-controlled, dose -escalation clinical study to evaluate the safety, tolerability and pharmacokinetics of ENC0653 ointment following single and multiple topical dermal administration in healthy adult subjects. Up to 56 subjects will be enrolled at a single site in up to 4 cohorts in Part A (SAD study), and up to 3 cohorts in Part B (MAD study). Part A is for the single dose use of IP, while Part B is twice-daily use for 7 consecutive days and once daily use on Day 8. Each cohort will include 8 subjects (6 receiving ENC0653 ointment and 2 receiving placebo ointment). Dosing will be escalated on a review of safety, tolerability, and available PK data by a Safety Review Committee (SRC).

Interventions

• Drug Low Dose, 10%BSA
  Topical dermal administration
• Drug Low Dose, 20%BSA
  Topical dermal administration
• Drug Middle Dose, 20%BSA
  Topical dermal administration
• Drug High Dose, 20%BSA
  Topical dermal administration
• Drug Low Dose, 20%BSA
  Topical dermal administration
• Drug Middle Dose, 20%BSA
  Topical dermal administration
• Drug High Dose, 20%BSA
  Topical dermal administration
• Drug Placebo
  Topical dermal administration

Primary outcome measures

• Number and types of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) following ENC0653 ointment administration [Time frame: D-28 to Day 4 (± 1) for SAD and D-28 to Day 11 (± 1) for MAD]

Secondary outcome measures (1)

• Plasma drug concentrations [Time frame: Single Ascending Dose (SAD) part: up to Day 4, 72 hours post dose; Multiple Ascending Dose (MAD) part: up to Day 11, 72 hours post last dose]

Eligibility criteria

Inclusion criteria

• The subject signs the informed consent form (ICF) prior to enrollment after full disclosure of study procedures and requirements. The subject understands the necessity of following study rules and completing all assessments on time, is fully informed of study procedures, and potential adverse reactions, and is able to complete the study in accordance with the protocol requirements.
• Aged ≥ 18 years and ≤ 55 years on the date of signing the informed consent form, male or female.
• Male subjects with body weight ≥ 50 kg, female subjects with body weight ≥ 45 kg, and body mass index (BMI) within the range of 18.0-32.0 kg/m² (inclusive).
• No ulceration, injury, sunburn, erythema, rash, or abnormal warmth, as well as tattoos, birthmarks, skin scars, or skin perforations shall be present on the target application regions at screening and prior to dosing.
• The subject gives voluntary consent to employ adequate contraceptive methods from 2 weeks prior to dosing until 1 month after the last study visit, and to refrain from sperm or egg donation during this period.

Exclusion criteria

• The subject has any skin disorders deemed by the investigator to be a study contraindication or to compromise assessment of the application region, including psoriasis, eczema, acne, atopic dermatitis, dysplastic nevi, other dermatologic lesions, or a history of cutaneous malignancy.
• Presence of any of the following high-risk conditions: history of deep vein thrombosis, arterial thrombosis, or pulmonary embolism; family history of thromboembolism (e.g., myocardial infarction or cerebral infarction in family members); history of malignancy; serious organ or systemic disease, immune-mediated disease (including but not limited to rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, Crohn's disease, psoriatic arthritis, etc.), or any diseases deemed by the investigator to render the subject unsuitable for enrollment in this study.
• Presence of any active cutaneous infections of acute bacterial, fungal, or viral (e.g., herpes simplex, herpes zoster, varicella, etc.) within 1 week prior to signing the ICF; or any acute or chronic infections requiring systemic treatment with antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to signing the ICF.
• History of severe trauma or major surgery within 3 months prior to screening; plan to receive surgery during the trial or within 2 weeks after completion of the trial.
• History of active tuberculosis, or clinical symptoms/signs or chest X-ray findings suggestive of active tuberculosis.
• Positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus (HIV) antibody, or Treponema pallidum antibody (TP-Ab).
• Pregnant, breast-feeding and/or lactating women.
• ALT, AST or TBiL ≥1.5ULN
• Has received any live vaccines within 1 month prior to screening or intend to receive a live vaccine during the study period or within 30 days after the last dose.
• The subject who has participated in any clinical trial of investigational drugs or medical devices within 3 months prior to screening (or 5 half-lives, whichever is longer).
• Other factors considered inappropriate for inclusion in this study at the discretion of the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Xuhui Central Hospital — Shanghai

Identifiers

NCT: NCT07684196 · ENC0653-P1-CN-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗