HIV/AIDSEarly Phase 1NCT04870671

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

A Early Phase 1 study testing Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) in people with HIV/AIDS and Adherence, Medication, run by Eastern Virginia Medical School at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 50 years, women onlyHealthy volunteers can take part
Conditions the study is for: HIV/AIDS, Adherence, Medication, Drug Use
What is being tested?: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: 25 Mar 2021to 31 Jan 2023
Phase: Early Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

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

Show all 14Show fewer

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Clinical Research Center, Eastern Virginia Medical School
Norfolk, Virginia, 23507

Other trials in United States

About this study

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)

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.

Read the 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 Hepatitis B 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 Liquid Chromatography-Tandem Mass Spectrometry (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.

Conditions: HIV/AIDS, Adherence, Medication, Drug Use
Being tested: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)
Keywords: HIV PrEP, biosensor, tenofovir
Medical subject headings: Acquired Immunodeficiency Syndrome, Medication Adherence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)Drug
Also called Truvada
Women will take 1 pill orally according the dosing regimen of the arm to which they are assigned

Study groups in NCT04870671
Study group	Role	What they receive
High Adherence	Experimental	TDF/FTC (300/200 mg), 7 pills/week. Total of 14 pills Receives: Drug: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)
Low Adherence	Experimental	TDF/FTC (300/2200 mg), 3 pills/week. Total of 6 pills Receives: Drug: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 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
Measured: 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
Measured: 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Mar 202131 Jan 2023

First posted3 May 2021
Study start25 Mar 2021
Primary completion31 Jan 2023
Study completion31 Jan 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for HIV/AIDSStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Model description: Women will be randomized into one of two groups: high adherence (7 pills/week) and how adherence (3 pills/week)
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04870671
Sponsor's protocol ID: 19-08-FB-0195
Other IDs: 5R21AI145809-02
Status last verified: Jan 2024
First submitted: 23 Apr 2021
Last updated: 30 Jan 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 27242994
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.
PubMed 26414912
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.
PubMed 24784763

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT04870671
Acronym / sponsor ID: 19-08-FB-0195
Conditions: HIV/AIDS, Adherence, Medication, Drug Use
Keywords: HIV PrEP, biosensor, tenofovir
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 14 participants (actual)
Lead sponsor: Eastern Virginia Medical SchoolUniversity, hospital or other
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Study start: 25 Mar 2021 (actual)
Primary completion: 31 Jan 2023 (actual)
Study completion: 31 Jan 2023 (actual)
First posted: 3 May 2021 (actual)
Results: Posted 30 Jan 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2
Model description: Women will be randomized into one of two groups: high adherence (7 pills/week) and how adherence (3 pills/week)

Arm	Type	Receives
High Adherence	Experimental	Drug: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)TDF/FTC (300/200 mg), 7 pills/week. Total of 14 pills
Low Adherence	Experimental	Drug: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)TDF/FTC (300/2200 mg), 3 pills/week. Total of 6 pills

Who may qualify

Ages: 18 to 50 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (14 listed)

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

Key exclusion criteria (8 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)Also: TruvadaWomen will take 1 pill orally according the dosing regimen of the arm to which they are assigned	Drug	High Adherence, Low Adherence

Primary outcome

Baseline TFV (Tenofovir) Levels in Plasma
Time frame: Baseline (pre-dose)
TFV levels will be measured by the TFV aptasensor and compared to Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) values
Levels of TFV in Plasma After Different Lengths of Time Post-first Dose
Time frame: 1 day
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
Time frame: 7 days
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
Time frame: 14 days
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values

Results and safety

Results posted to the registry on 30 Jan 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
High Adherence	7	7
Low Adherence	7	7

Primary outcome: Baseline TFV (Tenofovir) Levels in Plasma

Time frame: Baseline (pre-dose)

Population analysed: The development of the aptasensor did not reach the target endpoint of detecting TFV in human plasma samples

Primary outcome: Levels of TFV in Plasma After Different Lengths of Time Post-first Dose

Time frame: 1 day

Population analysed: The development of the aptasensor did not reach the target of detecting TFV in human plasma samples

Primary outcome: Levels of TFV in Plasma After Different Lengths of Time Post-first Dose

Time frame: 7 days

Population analysed: The development of the aptasensor did not reach the target of detecting TFV in human plasma samples

Primary outcome: Levels of TFV in Plasma After Different Lengths of Time Post-first Dose

Time frame: 14 days

Population analysed: The development of the aptasensor did not reach the target of detecting TFV in human plasma samples.

Adverse events

Time frame: 4 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
High Adherence	0 of 7 (0%)	2 of 7 (28.6%)	0 of 7
Low Adherence	0 of 7 (0%)	2 of 7 (28.6%)	0 of 7

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27242994Ruscito 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.
Background: PubMed 26414912Hendrix 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.
Background: PubMed 24784763Donnell 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Terry A Jacot, PhD principal investigator

Eastern Virginia Medical School

Andrea R Thurman, MD principal investigator

Eastern Virginia Medical School

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Baseline TFV (Tenofovir) Levels in Plasma (time frame: Baseline (pre-dose)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04870671, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2024.