Back to resultsProject ADHERE: Clinical Proof-of-Concept of a Tenofovir (TFV) Aptamer-Based Biosensor
Primary Purpose
HIV/AIDS, Adherence, Medication, Drug Use
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tenofovir Disoproxil Fumarate
Sponsored by
About this trial
This is an interventional diagnostic trial for HIV/AIDS focused on measuring HIV PrEP, biosensor, tenofovir
Eligibility Criteria
Inclusion Criteria:
- 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 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
Exclusion Criteria:
- 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
Sites / Locations
- Clinical Research Center, Eastern Virginia Medical School
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
High Adherence
Low Adherence
Arm Description
TDF/FTC (300/200 mg), 7 pills/week. Total of 14 pills
TDF/FTC (300/2200 mg), 3 pills/week. Total of 6 pills
Outcomes
Primary Outcome Measures
Baseline TFV levels in plasma
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
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
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
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
Secondary Outcome Measures
Baseline TFV levels in urine
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values (urine only)
Levels of TFV in urine after different lengths of time post-first dose
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Levels of TFV in urine after different lengths of time post-first dose
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Levels of TFV in urine after different lengths of time post-first dose
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Baseline TFV levels in vaginal fluid
TFV levels will be measured by the TFV aptasensor
Levels of TFV in vaginal fluid after different lengths of time post-first dose
TFV levels will be measured by the TFV aptasensor
Levels of TFV in vaginal fluid after different lengths of time post-first dose
TFV levels will be measured by the TFV aptasensor
Levels of TFV in vaginal fluid after different lengths of time post-first dose
TFV levels will be measured by the TFV aptasensor
Full Information
NCT ID
NCT04870671
First Posted
April 23, 2021
Last Updated
April 12, 2022
Sponsor
Eastern Virginia Medical School
1. Study Identification
Unique Protocol Identification Number
NCT04870671
Brief Title
Project ADHERE: Clinical Proof-of-Concept of a Tenofovir (TFV) Aptamer-Based Biosensor
Official Title
Project ADHERE: Clinical Proof-of-Concept of a Tenofovir (TFV) Aptamer-Based Biosensor for Determining Adherence Using Different Dosing Regimens of Disoproxil Fumarate/Emtricitabine (TDF/FTC)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
March 8, 2021 (Actual)
Primary Completion Date
August 13, 2021 (Actual)
Study Completion Date
August 13, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Eastern Virginia Medical School
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
Project ADHERE is a pilot, prospective, randomized study which will screen approximately 20 healthy, non-pregnant, HIV negative, premenopausal women (aged 18-50) at Eastern Virginia Medical School (EVMS) who are not at risk of pregnancy and are at low risk for sexually transmitted infections (STIs) in order to have approximately 14 women complete all study visits. The women will be randomized to one of two different dosing regimens of Truvada for up to 14 days. The low adherence cohort will take a total of 3 Truvada pills per week while the high adherence cohort will be assigned to take daily dosing, 7 pills per week. At screening (visit 1), we will screen women for HIV-1 and perform STI tests and serum screening for HepB and creatinine clearance prior to commencing oral PrEP, consistent with oral PrEP initiation guidelines. After screening labs return, they will come to the clinic for visit 2 when baseline blood, urine, and vaginal fluid will be collected, randomize participants to the dosing regimen, watch the participants ingest the first dose, and then direct to them to take subsequent doses in their homes. Reminder text messages will be sent to the participants to facilitate doses being taken at the same time of day upon which they will text message the coordinator after ingesting the pill. Participants will return 24 hours, 7 days, and 14 days after visit 2 for pre-dose collection of blood, urine, and vaginal fluid samples (visits 3, 4, and 5, respectively). For all visits, participants will not to take the next prescribed dose before coming to the clinic. Once samples are collected, participants will ingest the next scheduled pill. However, for the high adherence regimen, the women will take their last dose on day 14 and then come to the clinic 24 hours later on day 15 for collection of samples. Regardless of regimen, sample collection will take place no earlier than 24 hours after last dosing to prevent white coat effects. Samples will be brought to the laboratory for processing and eventual measurement of TFV levels by the TFV aptasensor. Aliquots of plasma and urine will also be analyzed by LC-MS/MS so sensitivity and specificity of the aptasensor can be determined. The ability of the TFV aptasensor to distinguish levels associated with high and low adherence will also be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV/AIDS, Adherence, Medication, Drug Use
Keywords
HIV PrEP, biosensor, tenofovir
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Women will be randomized into one of two groups: high adherence (7 pills/week) and how adherence (3 pills/week)
Masking
Outcomes Assessor
Masking Description
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
Allocation
Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
High Adherence
Arm Type
Experimental
Arm Description
TDF/FTC (300/200 mg), 7 pills/week. Total of 14 pills
Arm Title
Low Adherence
Arm Type
Experimental
Arm Description
TDF/FTC (300/2200 mg), 3 pills/week. Total of 6 pills
Intervention Type
Drug
Intervention Name(s)
Tenofovir Disoproxil Fumarate
Other Intervention Name(s)
Truvada
Intervention Description
Women will take 1 pill orally according the dosing regimen of the arm to which they are assigned
Primary Outcome Measure Information:
Title
Baseline TFV levels in plasma
Description
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Time Frame
Baseline (pre-dose)
Title
Levels of TFV in plasma after different lengths of time post-first dose
Description
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Time Frame
24 hours
Title
Levels of TFV in plasma after different lengths of time post-first dose
Description
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Time Frame
7 days
Title
Levels of TFV in plasma after different lengths of time post-first dose
Description
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Baseline TFV levels in urine
Description
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values (urine only)
Time Frame
Baseline (pre-dose)
Title
Levels of TFV in urine after different lengths of time post-first dose
Description
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Time Frame
24 hours
Title
Levels of TFV in urine after different lengths of time post-first dose
Description
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Time Frame
7 days
Title
Levels of TFV in urine after different lengths of time post-first dose
Description
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
Time Frame
14 days
Title
Baseline TFV levels in vaginal fluid
Description
TFV levels will be measured by the TFV aptasensor
Time Frame
Baseline (pre-dose)
Title
Levels of TFV in vaginal fluid after different lengths of time post-first dose
Description
TFV levels will be measured by the TFV aptasensor
Time Frame
24 hours
Title
Levels of TFV in vaginal fluid after different lengths of time post-first dose
Description
TFV levels will be measured by the TFV aptasensor
Time Frame
7 days
Title
Levels of TFV in vaginal fluid after different lengths of time post-first dose
Description
TFV levels will be measured by the TFV aptasensor
Time Frame
14 days
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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 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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terry A Jacot, PhD
Organizational Affiliation
Eastern Virginia Medical School
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andrea R Thurman, MD
Organizational Affiliation
Eastern Virginia Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Research Center, Eastern Virginia Medical School
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27242994
Citation
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.
Results Reference
background
PubMed Identifier
26414912
Citation
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.
Results Reference
background
PubMed Identifier
24784763
Citation
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.
Results Reference
background
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Project ADHERE: Clinical Proof-of-Concept of a Tenofovir (TFV) Aptamer-Based Biosensor
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