A Clinical Study of the HIV Drug CPT31 in Healthy Volunteers

A Phase Ia Clinical Study of HIV Entry Inhibitor CPT31: Single Ascending Dose Study of Safety, Tolerability, Immunogenicity, and Pharmacokinetics in Healthy Adults

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Placebo; Drug: CPT31

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 6 subjects receiving a single subcutaneous injection of CPT31 (0.01 mg/kg) and 2 subjects receiving matching placebo SC injection	Drug: Placebo; matching placebo; Drug: CPT31; CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer; Other Names: cholesterol-PIE12-2-trimer; cholesterol-PIE12-trimer
Experimental: Cohort 2; 6 subjects receiving a single subcutaneous injection of CPT31 (0.04 mg/kg) and 2 subjects receiving matching placebo SC injection	Drug: Placebo; matching placebo; Drug: CPT31; CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer; Other Names: cholesterol-PIE12-2-trimer; cholesterol-PIE12-trimer
Experimental: Cohort 3; 6 subjects receiving a single subcutaneous injection of CPT31 (0.12 mg/kg) and 2 subjects receiving matching placebo SC injection	Drug: Placebo; matching placebo; Drug: CPT31; CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer; Other Names: cholesterol-PIE12-2-trimer; cholesterol-PIE12-trimer
Experimental: Cohort 4; 6 subjects receiving a single subcutaneous injection of CPT31 (0.24 mg/kg) and 2 subjects receiving matching placebo SC injection	Drug: Placebo; matching placebo; Drug: CPT31; CPT31 (cholesterol-PIE12-2-trimer) is a novel D-peptide HIV entry inhibitor that binds with high affinity to a conserved hydrophobic pocket within the gp41 trimer; Other Names: cholesterol-PIE12-2-trimer; cholesterol-PIE12-trimer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of subjects experiencing serious adverse events (SAEs)	Check-in (Day -1) through Follow-up (Day 28-30)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	maximum observed plasma concentration (ng/mL)	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	time of maximum observed plasma concentration (h)	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)
T1/2	apparent plasma terminal elimination half-life (h)	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-∞	area under the concentration versus time curve (AUC) from time zero to infinity (h*ng/mL)	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	area under the concentration versus time curve (AUC) from time zero to time of the last quantifiable concentration (h*ng/mL)	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)
Total Plasma Clearance (CL/F)	apparent total plasma clearance (L/h/kg)	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	apparent volume of distribution (L/kg)	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	amount of drug excreted in the urine (ng/mL)	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	percentage of dose excreted unchanged in the urine (%)	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)	renal clearance (L/h/kg)	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	Number of subjects with measurable levels of anti-CPT31 antibodies in serum	Pre-dose on Day 1 through Follow-up (Day 28-30)

Collaborators and Investigators

• Sponsor: Navigen, Inc.
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Covance

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2020
• Primary Completion (Actual): April 26, 2021
• Study Completion (Actual): April 29, 2021

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 14, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: D-peptide HIV entry inhibitor
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: CPT31-001; 2U44AI095172-08 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No