ENLIGHTEN: Establishing Novel Antiretroviral (ARV) Imaging for Hair to Elucidate Non-Adherence

NCT03218592 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 17-05461R01AI122319-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: Perform a 3-phase (single dose, multi dose, dose proportionality) study in healthy volunteers using daily tenofovir+emtricitabine, dolutegravir, and maraviroc dosing to quantify intra- and inter-subject variability and dose proportionality. The influence of covariates on ARV hair distribution (e.g., hair growth rate, race, hair color, hair treatment) will also be measured. Using both population PK modeling and physiologic based PK (PBPK) approaches, a statistical model to quantify ARV adherence patterns based on signal intensity/pattern will be developed. Participants: Healthy volunteers, aged 18 to 70 years of age, inclusive on the date of screening, with an intact gastrointestinal system and at least 1cm caput hair. Procedures (methods): Participants will be sequentially assigned to enroll in a dosing arm, beginning with maraviroc (MVC), then dolutegravir (DTG), and ending with tenofovir/emtricitabine (TFV/FTC). All participants will take a single observed dose of study product in Phase 1, with blood and hair samples obtained on Days 3, 7, 14, 21 and 28 days post-dose. In Phase 2, all participants take 28 days straight of daily dosing, observed, of the same study product. Blood and hair samples obtained on the same days post-dose. In Phase 3, participants will be randomized to stop their drug, or decrease dosing to one or three doses weekly. Hair and blood samples will again be obtained on the same days post-dose. All participants will complete a follow-up safety visit with 14 days of completing study sampling.

Conditions

HIV/AIDS

Keywords

Adherence; Hair

Outcome Measures

Primary Outcomes (1)

• Hair Antiretroviral Imaging

  Signal Strength concentrations will be measured in hair for all study drugs, inclusive of FTC (emtricitabine), tenofovir (TFV), maraviroc (MRV), and dolutegravir (DTG) using Matrix-assisted Laser Desorption Electrospray Ionization (IR-MALDESI) to be reported by signal abundance (au). Signal abundance is the industry standard unit, and higher values represent greater signal with capability to relate to comparative concentrations.

  Up to 28 days post dose

Secondary Outcomes (3)

• Peripheral Blood Mononuclear Cells (PBMC) Antiretroviral Concentrations

  Up to 28 days post-dose

• Plasma Antiretroviral Concentrations

  Up to 28 days post-dose

• Whole Blood Antiretroviral Concentrations

  Up to 28 days post-dose

Study Arms (3)

Maraviroc

EXPERIMENTAL

12 Healthy subjects will dose with Maraviroc Pill and we will collect blood and hair over all three phases

Drug: Maraviroc Pill

Dolutegravir

EXPERIMENTAL

12 Healthy volunteers will dose with Dolutegravir Pill and we will collect blood and hair over all three phases

Drug: Dolutegravir Pill

Truvada

EXPERIMENTAL

12 healthy volunteers will dose with Truvada Pill and we will collect blood and hair over all three phases

Drug: Truvada Pill

Interventions

Maraviroc Pill DRUG

Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly

Also known as: selzentry

Maraviroc

Dolutegravir Pill DRUG

Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly

Also known as: Tivicay

Dolutegravir

Truvada Pill DRUG

Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weeklySubjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly

Also known as: Tenofovir/Emtricitabine

Truvada

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteer between the ages of 18 and 70, inclusive on the date of screening, with an intact gastrointestinal tract. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, and clinical laboratory tests
• Recent medical history in good medical standing, without evidence of fever five days prior to enrollment
• HIV-negative
• Able to swallow pills
• Has minimum hair required to provide study samples
• Not allergic to any component of the study drug
• Signed and dated informed consent indicating that they have been informed of all pertinent details of the trial and are willing to participate
• Willing and able to comply with scheduled visits, laboratory tests and trial procedures
• Willing to use at least one form of acceptable birth control throughout the duration of the study
• Negative, or receiving treatment, for syphilis at screening
• Hemoglobin Grade 2 or lower, with no clinically significant medical issues that would preclude blood sampling

You may not qualify if:

• Age outside of desired range
• Confirmed positive results for HIV, Hepatitis B or C at screening
• Subjects of all genders actively involved in the conception process, in addition to cisgender female subjects who are in the immediate post-partum period or breastfeeding
• Insufficient amount of hair or unwilling to keep hair length at least 1 centimeter throughout duration of study
• Unable or unwilling to comply with all lifestyle measures and/or visits
• Impaired renal function, as documented by a creatinine clearance \<80 mL/min with the Cockcroft-Gault equation
• Has donated blood within the past 56 days in the amount greater than 500 mL
• Has taken an investigational drug in the past 4 months
• Clinical, laboratory, or surgical abnormalities that would preclude sample collection
• Has a condition, which, in the opinion of the investigator, is likely to interfere with follow-up or ability to take the study medication appropriately
• Any clinically significant laboratory result Grade 2 or greater according to the Division of AIDS (DAIDS) Laboratory Grading Tables
• History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) per week

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Clinical and Translational Research Center, UNC Hospitals

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Hill LM, Golin CE, Pack A, Carda-Auten J, Wallace DD, Cherkur S, Farel CE, Rosen EP, Gandhi M, Asher Prince HM, Kashuba ADM. Using Real-Time Adherence Feedback to Enhance Communication About Adherence to Antiretroviral Therapy: Patient and Clinician Perspectives. J Assoc Nurses AIDS Care. 2020 Jan-Feb;31(1):25-34. doi: 10.1097/JNC.0000000000000089.

  PMID: 31033629 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Maraviroc; dolutegravir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir; Emtricitabine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Angela Kashuba
• Organization: University of North Carolina at Chapel Hill

akashuba@unc.edu

9199969998

Study Officials

• Angela DM Kashuba, BScPhmPharmD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective. Single-center, open-label, 3-arm, triple stage study

Study Record Dates

• First Submitted: July 10, 2017
• First Posted: July 14, 2017
• Study Start: June 28, 2017
• Primary Completion: December 3, 2018
• Study Completion: December 7, 2018
• Last Updated: November 22, 2019
• Results First Posted: November 22, 2019

Record last verified: 2019-02

Locations

US (1)