a clinical study of the hiv drug cpt31 in healthy volunteers

Conditions: HIV Infections

Summary: 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.

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.

Eligibility criteria:
inclusion criteria: * 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. exclusion criteria: * 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 2017. * estimated glomerular filtration rate (egfr per ckd-epi equation) of \<90 ml/min/1.73 m2. * 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 -1. * 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 -1. * 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 -1. * receipt of blood products within 2 months prior to day -1. * 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.

Keywords: d-peptide hiv entry inhibitor