Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic (PK/PD) Profile of ACT100 in Healthy Participants..

Official title

A Single-Center, Randomized, Double-Blind, Dose-Escalation, Placebo-Controlled, Phase Ia Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic (PK/PD) Profile of ACT100 in Healthy Participants.

Overview

This study is a Phase Ia, single-center, randomized, double-blind, dose-escalation, placebo-controlled clinical trial designed to evaluate the safety, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) profile of ACT100 in healthy participants. A total of 6 dose cohorts are planned, with each cohort enrolling 8 participants (including both male and female participants, where 6 will receive the investigational drug and 2 will receive placebo). The total planned enrollment is 48 healthy participants.

Interventions

• Drug ACT100 Injection
  a single 5-mg subcutaneous injection
• Drug Placebo for ACT100
  a single 5-mg subcutaneous injection
• Drug ACT100 Injection
  a single 25-mg subcutaneous injection
• Drug Placebo for ACT100
  a single 25-mg subcutaneous injection
• Drug ACT100 Injection
  a single 100-mg subcutaneous injection
• Drug Placebo for ACT100
  a single 100-mg subcutaneous injection
• Drug ACT100 Injection
  a single 300-mg subcutaneous injection
• Drug Placebo for ACT100
  a single 300-mg subcutaneous injection
• Drug ACT100 Injection
  a single 600-mg subcutaneous injection
• Drug Placebo for ACT100
  a single 600-mg subcutaneous injection

Primary outcome measures

• Adverse Event(AE) [Time frame: Day 1-84]
• Serious Adverse Event [Time frame: Day 1-84]
• blood pressure [Time frame: Day 1-84]
• pulse [Time frame: Day 1-84]
• respiration [Time frame: Day 1-84]
• body temperature [Time frame: Day 1-84]
• Number of Participants with Abnormal Physical examination parameters [Time frame: Day 1-84]
• Number of Participants with Abnormal Laboratory Parameters Findings [Time frame: Day 1-84]
• Number of Participants with 12-Lead Electrocardiogram Findings [Time frame: Day 1-84]

Secondary outcome measures (11)

• Area Under the plasma concentration-time Curve from time zero to the last measurable concentration(AUC₀-t) [Time frame: Day 1-4,7,14,21,28,42,56,70,84]
• Area Under the plasma concentration-time Curve from time zero extrapolated to infinity(AUC₀-∞) [Time frame: Day 1-4,7,14,21,28,42,56,70,84]
• Maximum observed plasma concentration(Cmax) [Time frame: Day 1-4,7,14,21,28,42,56,70,84]
• Time to reach the maximum observed plasma concentration(Tmax) [Time frame: Day 1-4,7,14,21,28,42,56,70,84]
• Terminal elimination half-life(t1/2) [Time frame: Day 1-4,7,14,21,28,42,56,70,84]
• Apparent clearance (CL/F) [Time frame: Day 1-4,7,14,21,28,42,56,70,84]
• Apparent volume of distribution(Vd/F) [Time frame: Day 1-4,7,14,21,28,42,56,70,84]
• Levels of BDCA2 on the surface of plasmacytoid dendritic cells (pDCs) [Time frame: Day 1-3,7,14,28,42,56,70,84]
• Peripheral blood pDC levels [Time frame: Day 1-3,7,14,28,42,56,70,84]
• Anti-drug antibodies (ADA). [Time frame: Day 1,28,56,84]
• Neutralizing antibodies (NAb) [Time frame: Day 1,28,56,84]

Eligibility criteria

Inclusion criteria

• Participants must voluntarily participate and sign the informed consent form after being informed of the entire trial process and the potential adverse reactions of the investigational product.
• Healthy male and female participants aged between 18 and 55 years (inclusive) at the time of signing the informed consent form.
• Body mass index (BMI) at screening: 18.5 kg/m\^2 ≤ BMI < 28 kg/m\^2; body weight ≥ 50 kg (for males) / ≥ 45 kg (for females).
• At screening, physical examination, vital signs, laboratory tests, electrocardiogram (ECG), etc., are all normal or show abnormalities judged by the investigator as having no clinical significance.
• Females of childbearing potential and males must agree to use highly effective contraceptive methods (e.g., intrauterine device, condom) from screening until 3 months after administration of the investigational product and have no plan for sperm or egg donation.

Exclusion criteria

• History of treatment with any drug targeting the same molecule (BDCA2) as the investigational product.
• A 12-lead electrocardiogram (ECG) at screening showing abnormalities considered clinically significant by the investigator (e.g., QTcF > 450 ms for males or > 470 ms for females).
• History of severe diseases of major organ systems, including but not limited to neurological, cardiovascular, hematological, autoimmune, renal, hepatic, gastrointestinal, pulmonary, endocrine, metabolic, or psychiatric disorders.
• Presence of severe bacterial or viral infection (e.g., pneumonia, sepsis, herpes zoster), or fungal/parasitic infection within 2 months prior to screening; or any symptoms of active or suspected infection within 1 week prior to dosing.
• Chronic infectious diseases such as chronic hepatitis B or C, AIDS, tuberculosis, etc. Exclusion applies if any of the following tests are positive at screening: Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis C antibody (HCVAb), Treponema pallidum antibody, Human Immunodeficiency Virus antibody (HIVAb); or if there is evidence of active or latent Mycobacterium tuberculosis infection at screening.
• History of primary immunodeficiency, splenectomy, or any other underlying condition deemed by the investigator to confer a high risk of severe infection.
• History of severe food or drug allergy, or known allergy to monoclonal antibodies.
• Vaccination with a live attenuated vaccine within 1 month prior to screening, or any other vaccination within half a month prior to screening, or plans to receive any vaccine during the study period.
• Use of any prescription drugs, over-the-counter medications (including Chinese herbal medicines, health supplements, etc.) within 14 days prior to the first dose of the investigational product, unless deemed by both the investigator and sponsor to have no impact on the study.
• History of drug abuse, illicit drug use, or alcohol abuse (history of drug abuse or illicit drug use within the past 5 years; or habitual alcohol intake exceeding 14 units per week within 3 months prior to screening: 1 unit ≈ 285 mL beer, or 25 mL spirits, or 100 mL wine). Participants with a positive alcohol breath test or positive urine drug abuse screening at screening will be excluded.
• Heavy smoking (averaging >5 cigarettes per day) within 3 months prior to screening, or unwillingness to refrain from smoking during the study period.
• Donation or loss of >400 mL of blood within 3 months prior to screening, or >200 mL within 1 month prior to screening; or receipt of blood transfusion or blood products within 3 months prior to screening.
• Participation in another clinical trial involving an investigational drug/therapy within 1 month prior to screening, or within 5 half-lives (based on the known half-life of the prior investigational product, the Investigator's Brochure, or the informed consent form, whichever specifies the longer period).
• History of blood/needle phobia or intolerance to venipuncture, or abnormalities at the potential injection site deemed by the investigator to be unsuitable for subcutaneous administration.
• Females who are pregnant or lactating.
• Any other condition that, in the judgment of the investigator, makes the participant unsuitable for participation in this study.

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

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07408908 · ACT100-4-1-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗