A Phase Ia Clinical Study of HIV Entry Inhibitor CPT31: Single Ascending Dose Study of Safety, Tolerability, Immunogenicity, and Pharmacokinetics in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Adverse Events
研究概览
简要总结
This first-in-human study will evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of the HIV entry inhibitor CPT31 (cholesterol-PIE12-2-trimer) in healthy adults. This is a randomized, placebo-controlled, double-blind, single ascending dose study.
详细描述
This is a single subcutaneous (SC) dose study. Doses will be administered in an escalating manner following satisfactory review by a Protocol Safety Review Team (PSRT) of the safety, tolerability and pharmacokinetic (PK) data through Day 6 from the lower dose levels. 32 healthy subjects will be studied in 4 groups (Groups A1 to A4).
This study will comprise a placebo-controlled, double-blind, single-dose, sequential-group design in healthy subjects. Each subject will participate in 1 treatment period and reside in the Clinical Research Unit (CRU) from Day -1 through Day 6. It is planned for 6 subjects per dose level group to receive SC CPT31 and 2 subjects to receive matching placebo. Each group will be divided into 2 cohorts, with each cohort being dosed 72 hours apart. Sentinel dosing will take place in the first cohort, which will comprise 2 subjects, with 1 subject receiving CPT31 and 1 subject receiving placebo. The second cohort will comprise 6 subjects, with 5 subjects receiving CPT31 and 1 subject receiving placebo. Blood samples for PK analysis and assessment of immunogenicity will be collected predose and up to 5 days postdose, with an additional immunogenicity sample taken at the Follow-up visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males or females, of any race, between 18 and 55 years of age, inclusive.
- •Body mass index between 18.0 and 32.0 kg/m2, inclusive.
- •In good health, determined by no clinically significant findings from medical and surgical history, physical examination, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at Screening and/or Day -1 as assessed by the Investigator (or designee).
- •Females will not be pregnant or have been within the previous 3 months, or lactating, and females of childbearing potential and males will agree to use contraception.
- •Able to comprehend and willing to sign an Informed Consent Form (ICF) and to abide by the study restrictions.
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
- •A ≥Grade 2 laboratory abnormality at Screening or Day -1 as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July
- •Estimated glomerular filtration rate (eGFR per CKD-Epi equation) of <90 ml/min/1.73 m
- •Known sensitivity to CPT31 or any of its components.
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
- •History of alcoholism or drug/chemical abuse within 2 years prior to Day -
- •Alcohol consumption of > 21 units per week for males and > 14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
- •Positive urine drug screen at Screening or positive alcohol breath test result or positive urine drug screen on Day -
- •Positive HIV test as documented by Combo Ag/Ab HIV 1/HIV-2 immunoassay.
- •Positive hepatitis B surface antigen, positive hepatitis B core antibody with negative hepatitis B surface antibody test result, or positive hepatitis C antibody at Screening or within 3 months before first dose of study treatment.
- •Participation in a clinical study involving administration of an investigational drug in the past 30 days prior to dosing.
- •Use or intend to use any prescription or over the counter medications/products (including HIV medications being used for pre-exposure prophylaxis) other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives or acetaminophen up to 2 grams per day for no more than 3 consecutive days within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
- •Use of tobacco or nicotine containing products within 3 months prior to Day -1, or positive cotinine at Screening or Day -
- •Receipt of blood products within 2 months prior to Day -
- •Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
- •Poor peripheral venous access.
- •Have previously completed or withdrawn from this study or any other study investigating CPT31 and have previously received the investigational product.
- •Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
- •Have any clinically significant abnormal ECG results constituting a risk while taking the investigational product, as determined by the Investigator, such as any of the following, as determined by single 12-lead ECG: QT interval corrected for heart rate using Fridericia's method (QTcF) >450 ms for males and >470 ms for females, confirmed by calculating the mean of the original value and 2 repeats; QRS duration >120 ms confirmed by calculating the mean of the original value and 2 repeats; PR interval >220 ms confirmed by calculating the mean of the original value and 2 repeats; findings which would make QTc measurements difficult or QTc data uninterpretable; history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome); risks related to bradycardia, for example, second or third degree atrioventricular block or sick sinus syndrome.
研究组 & 干预措施
Cohort 1
6 subjects receiving a single subcutaneous injection of CPT31 (0.01 mg/kg) and 2 subjects receiving matching placebo SC injection
干预措施: CPT31 (Drug)
Cohort 1
6 subjects receiving a single subcutaneous injection of CPT31 (0.01 mg/kg) and 2 subjects receiving matching placebo SC injection
干预措施: Placebo (Drug)
Cohort 2
6 subjects receiving a single subcutaneous injection of CPT31 (0.04 mg/kg) and 2 subjects receiving matching placebo SC injection
干预措施: CPT31 (Drug)
Cohort 2
6 subjects receiving a single subcutaneous injection of CPT31 (0.04 mg/kg) and 2 subjects receiving matching placebo SC injection
干预措施: Placebo (Drug)
Cohort 3
6 subjects receiving a single subcutaneous injection of CPT31 (0.12 mg/kg) and 2 subjects receiving matching placebo SC injection
干预措施: CPT31 (Drug)
Cohort 3
6 subjects receiving a single subcutaneous injection of CPT31 (0.12 mg/kg) and 2 subjects receiving matching placebo SC injection
干预措施: Placebo (Drug)
Cohort 4
6 subjects receiving a single subcutaneous injection of CPT31 (0.24 mg/kg) and 2 subjects receiving matching placebo SC injection
干预措施: CPT31 (Drug)
Cohort 4
6 subjects receiving a single subcutaneous injection of CPT31 (0.24 mg/kg) and 2 subjects receiving matching placebo SC injection
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse Events
时间窗: Check-in (Day -1) through Follow-up (Day 28-30)
Number of subjects experiencing serious adverse events (SAEs)
次要结局
- Total Plasma Clearance (CL/F)(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))
- Area Under the Concentration Curve (AUC) 0-∞(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))
- AUC0-tlast(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))
- Cmax(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))
- Tmax(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))
- Ae(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))
- Renal Clearance (CLR)(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))
- Immunogenicity(Pre-dose on Day 1 through Follow-up (Day 28-30))
- T1/2(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))
- Vz/F(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))
- Fe(Day 1 predose, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, Day 2 (24 h), Day 3 (48 h), Day 4 (72 h), Day 5 (96 h), and Day 6 (120 h))