Healthy Volunteer Study
Conditions
Keywords
Phase 1 study of AK0610
Brief summary
The study consists of two parts: dose escalation and expansion. It includes five cohorts in the dose-escalation phase and two expansion cohorts based on pharmacokinetic data.
Detailed description
This study is a Phase I clinical trial that is randomized, double-blind, placebo-controlled, and involves single-dose administration, dose-escalation, and an expansion phase. It evaluates the safety, tolerability, and pharmacokinetic profile of AK0610 in healthy Chinese adults. The study consists of two parts. The dose-escalation phase includes five cohorts (100 mg i.m.; 300 mg i.m.; 300 mg i.v.; 1000 mg i.v.; 3000 mg i.v.), each consisting of 8 individuals (AK0610: Placebo = 3:1), who are administered doses in sequential increments. Based on pharmacokinetic data, the dose-escalation phase will be expanded to include two additional dose cohorts (300 mg i.m.; 600 mg i.m.) of 48 individuals each (AK0610: Placebo = 3:1). Each participant will undergo a Screening Period from Day -29 to Day -1. They will receive one dose on Day 1, an Inpatient Observation Period from Day -1 to Day 8, and a Blinded Follow-Up Period from Day 9 to Day 181. Subjects in the AK0610 group will also enter an open-label period from Day 182 to Day 361.
Interventions
DRUGAK0610 Injection solution
Active Substance: AK0610 Pharmaceutical Form: Injection solution Route of Administration: Intramuscular injection or intravenous injection.
DRUGPlacebo
Active Substance: Placebo Pharmaceutical Form: Injection Route of Administration: Intramuscular injection or intravenous injection
Sponsors
Shanghai Ark Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants aged 18 - 50 (both males and females) 2. Males weighing ≥50 kg, females weighing ≥45 kg, and BMI 18-28 kg/m2. 3. Assessed by the investigator to be in good health with no clinically significant abnormalities. 4. Use of highly effective contraception within 1 year of administration. 5. Voluntary participation in clinical research and signing of written informed consent.
Exclusion criteria
1. Clinically significant cardiovascular, respiratory, hepatic, renal, hematologic (e.g., bleeding disorders), gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric system disorders, or any other condition that, in the opinion of the Investigator, may jeopardize subject safety or validity of the study results, or that may result in the inability of the subject to complete the study in accordance with the protocol. 2. Active malignancy and/or a history of malignancy (except for basal cell carcinoma of the skin that has been treated without evidence of recurrence) 3. History of congenital or acquired immunodeficiency. 4. Acute illness, such as fever, infectious disease, diarrhea, etc., occurring within 1 week prior to the subject's first dose. 5. Major surgery within 3 months prior to screening or major surgery planned within 1 year of study drug administration. 6. Hypersensitivity to the active ingredient of AK0610 or any excipients. 7. Previous history of allergy to biologics or history of severe allergic reaction (e.g. hypotension, dyspnea, severe angioedema) to any drug. 8. Human immunodeficiency virus (HIV) antibody positive; hepatitis C virus (HCV) antibody positive or hepatitis B surface antigen (HBsAg) positive; syphilis spirochete antibody positive. 9. Systolic blood pressure ≥140 mmHg or \<90 mmHg or diastolic blood pressure ≥90 mmHg or \<60 mmHg, and pulse \<55 or \>100 beats/min. 10. ECG suggestive of prolonged QTcF (≥450 ms in both women and men). \[QTcF= QT/(RR\^0.33)\] 11. Use of any prescription, over-the-counter, herbal, proprietary, or health care product (other than birth control pills) within 14 days prior to study drug administration. 12. Have received treatment with immune globulin or other blood products within 6 months prior to study drug administration 13. Have received treatment with monoclonal antibodies or other biological products within 6 months prior to administration of study drug. 14. Have received a live attenuated vaccination within 1 month prior to study drug administration, has received another vaccination within 14 days, or is scheduled to receive a vaccination within 1 year of study drug administration. 15. Received any other investigational drug therapy within 3 months (or 5 half-lives, whichever is longer) prior to study drug administration, or plans to participate in another study within 1 year of study drug administration. 16. Participating or have participated in another interventional clinical study of a monoclonal antibody or vaccine against RSV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs) | Up to 361 days | Capture the incidence and severity of adverse events using CTCAE v5.0, documenting all treatment-emergent adverse events (TEAEs) throughout the study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Serum Concentration (Tmax) of AK0610 | Up to 361 days | The Tmax is defined as time at which maximum observed concentration of AK0610 (Cmax) was observed. |
| Area Under the serum concentration-time curve from time 0 to the last measurable concentration (AUC₀-t) of AK0610 | Up to 361 days | It represents the area under the curve of serum concentration versus time for the drug AK0610 from the time of administration until the last measurable concentration. |
| Area Under the serum concentration-time curve from time 0 to extrapolated to infinite time (AUC (0-infinity) ) of AK0610 | Up to 361 days | The pharmacokinetic (PK) parameter AUC (0-infinity) was estimated based on the serum concentrations of AK0610. |
| Terminal Elimination Half Life (t1/2) of AK0610 | Up to 361 days | Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum. |
| Extravascular Clearance (CL/F (intramuscular administration)) of AK0610 | Up to 361 days | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Maximum Observed Serum Concentration (Cmax) of AK0610 | Up to 361 days | The Cmax is the maximum observed serum concentration of AK0610. |
| CL(IV administration) of AK0610 | Up to 361 days | Clearance (CL) following intravenous administration will be calculated to quantify the rate of drug elimination from plasma. |
| Vd (IV administration) of AK0610 | Up to 361 days | Volume of distribution (Vd) after intravenous dosing will be estimated to characterize the drug's tissue penetration relative to plasma |
| To assess the changes in serum RSV-neutralizing activity after a single intramuscular or intravenous injection of AK0610 in healthy Chinese subjects | Up to 361 days | Changes in serum anti-RSV neutralizing antibody titers |
| To assess the immunogenicity of a single intramuscular or intravenous injection of AK0610 in healthy Chinese subjects. | Up to 361 days | Serum positivity and titer of anti-drug antibodies against AK0610 |
| Apparent Volume of Distribution (Vd/F (intramuscular administration)) of AK0610 | Up to 361 days | It represents the theoretical volume in which the drug is distributed in the body, calculated by dividing the dose by the concentration in the terminal elimination phase. |
Countries
China
Contacts
Primary ContactNina Shen
Outcome results
None listed