Project ADHERE: Clinical Proof-of-Concept of a Tenofovir (TFV) Aptamer-Based Biosensor

NCT04870671 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 19-08-FB-01955R21AI145809-02
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Truvada®, an oral pill comprised of two anti-retroviral compounds, emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), is currently the only drug combination approved for pre-exposure prophylaxis (PrEP) in women exposed to high HIV risk through vaginal acquisition. Adherence to the one pill per day regimen is crucial for its effectiveness in reducing the risk of acquiring HIV. Currently, there is no available point of care diagnostic test to quickly measure blood levels of tenofovir in the clinic. This study will determine whether a tenofovir (TFV) aptamer-based biosensor (aptasensor) can detect TFV in biological fluids from women randomized to different dosing regimens representing high and low adherence.

Conditions

HIV/AIDS; Adherence, Medication; Drug Use

Keywords

HIV PrEP; biosensor; tenofovir

Outcome Measures

Primary Outcomes (4)

• Baseline TFV (Tenofovir) Levels in Plasma

  TFV levels will be measured by the TFV aptasensor and compared to Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) values

  Baseline (pre-dose)

• Levels of TFV in Plasma After Different Lengths of Time Post-first Dose

  TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values

  1 day

• Levels of TFV in Plasma After Different Lengths of Time Post-first Dose

  TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values

  7 days

• Levels of TFV in Plasma After Different Lengths of Time Post-first Dose

  TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values

  14 days

Study Arms (2)

High Adherence

EXPERIMENTAL

TDF/FTC (300/200 mg), 7 pills/week. Total of 14 pills

Drug: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)

Low Adherence

EXPERIMENTAL

TDF/FTC (300/2200 mg), 3 pills/week. Total of 6 pills

Drug: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)

Interventions

Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) DRUG

Women will take 1 pill orally according the dosing regimen of the arm to which they are assigned

Also known as: Truvada

High Adherence; Low Adherence

Eligibility Criteria

• Age: 18 Years - 50 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 50 years, inclusive
• General good health (by volunteer history and per investigator judgment) without any clinically significant systemic disease (including, but not limited to significant liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, osteoporosis or bone disease, and diabetes) and with an intact gastrointestinal tract, uterus and cervix.
• Estimated calculated creatinine clearance (eCcr) of at least 80 mL/min
• Body Mass Index (BMI) of ≥18 and \<35kg/m2; and a total body weight \>45 kg (99.2 lbs)
• Willing to give voluntary consent and sign an informed consent form
• Willing and able to comply with protocol requirements, including swallowing tablets
• Must be protected from pregnancy by:
• Condoms
• Hormonal contraceptives
• Copper or Levonorgestrel intrauterine device (IUD)
• Sterilization of either partner
• Heterosexual abstinence
• Same sex relationship
• If in a relationship, must be in a mutually monogamous relationship with a partner who is not known to be HIV positive and has no known risk of STIs

You may not qualify if:

• Currently pregnant
• Currently breastfeeding or planning to breastfeed during the course of the study
• In the last three months, diagnosed with or treated for any STI
• Positive test for HIV, or Hepatitis B surface antigen (HBsAg)
• Systemic use in the last two weeks or anticipated use during the study of any of the following: antiretrovirals (e.g. Viread®, Atripla®, Emtriva®, or Complera®), or drugs that may interact with TFV (e.g., protease inhibitors, anticonvulsants, antimycobacterials, St. John's Wort).
• Participation in any other investigational trial with use of a drug/device within the last 30 days or planned participation in any other investigational trial with use of a drug/device during the study
• Grade 2 or higher laboratory abnormality, per the 2014 update of the Division of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse Events, or clinically significant laboratory abnormality as determined by the clinician
• Abnormal finding on laboratory or physical examination or a social or medical condition in the volunteer which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data

Sponsors & Collaborators

• Eastern Virginia Medical School: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Clinical Research Center, Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

Related Publications (3)

• Ruscito A, DeRosa MC. Small-Molecule Binding Aptamers: Selection Strategies, Characterization, and Applications. Front Chem. 2016 May 10;4:14. doi: 10.3389/fchem.2016.00014. eCollection 2016.

  PMID: 27242994 BACKGROUND

• Hendrix CW, Andrade A, Bumpus NN, Kashuba AD, Marzinke MA, Moore A, Anderson PL, Bushman LR, Fuchs EJ, Wiggins I, Radebaugh C, Prince HA, Bakshi RP, Wang R, Richardson P, Shieh E, McKinstry L, Li X, Donnell D, Elharrar V, Mayer KH, Patterson KB. Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks (HPTN 066). AIDS Res Hum Retroviruses. 2016 Jan;32(1):32-43. doi: 10.1089/AID.2015.0182. Epub 2015 Oct 15.

  PMID: 26414912 BACKGROUND

• Donnell D, Baeten JM, Bumpus NN, Brantley J, Bangsberg DR, Haberer JE, Mujugira A, Mugo N, Ndase P, Hendrix C, Celum C. HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):340-8. doi: 10.1097/QAI.0000000000000172.

  PMID: 24784763 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Medication Adherence

Interventions

Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

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; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The project was successful in developing an aptasensor that could detect 1-30 nanomolar (nM) TFV in saline. However, the electrode configuration could not detect TFV in plasma due to interfering signals generated by the proteins present in the sample. Therefore, the aptasensor needs optimization before it can successfully be tested against the clinical samples of this clinical trial.

Results Point of Contact

• Title: Dr. Terry Jacot
• Organization: Eastern Virginia Medical School

jacotta@evms.edu

757-446-7056

Study Officials

• Terry A Jacot, PhD

  Eastern Virginia Medical School

  PRINCIPAL INVESTIGATOR

• Andrea R Thurman, MD

  Eastern Virginia Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: When measuring TFV levels in the biological fluids, the outcomes assessor in the laboratory will not know whether the samples are from the high or low adherence group
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant Professor

Model Details: Women will be randomized into one of two groups: high adherence (7 pills/week) and how adherence (3 pills/week)

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: May 3, 2021
• Study Start: March 25, 2021
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: January 30, 2024
• Results First Posted: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)