Validation of a Urine Assay to Measure Tenofovir Levels in Patients Taking Tenofovir Alafenamide

• Sponsor: Philadelphia Fight (Other)
• Overall Status: Completed
• CT.gov ID: NCT03350672
• Collaborator: Gilead Sciences (Industry)
• Enrollment: 37
• Location: 1
• Arms: 3
• Actual Duration (Months): 5.5
• Patients Per Site Per Month: 6.8

Study Details

Study Description

Brief Summary

Pre-exposure prophylaxis (PrEP) with Truvada™ (tenofovir/emtricitabine), in which an HIV-uninfected individual at high risk for contracting HIV takes antiretroviral medications (one pill daily) to maintain blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been validated in several large international trials that have included men who have sex with men and transgender women, heterosexual men and women, and people who use injection drugs, as a potential HIV-1 prevention strategy. HIV prevention interventions such as this, if adequately disseminated and implemented broadly, may help to curb new HIV infections, reduce HIV-associated morbidity and mortality, and reduce health disparities in HIV rates among the most at-risk individuals. Assuring adherence to a daily dose of PrEP is critical for effective protection against HIV infection. A urine-based test to measure PrEP medication levels in the body represents a non-invasive technique to assess adherence and ultimately improve PrEP's protective ability.

TAF/FTC (Descovy™) is a new medication under study for HIV prevention to see if it is as effective as Truvada™. This study is testing whether a urine test can detect this medication in urine.

Condition or Disease	Intervention/Treatment	Phase
Hiv	Drug: FTC/TAF	Phase 4

Detailed Description

Primary Objectives:

1a) To determine how long TFV is excreted in the urine in patients at steady state of TAF/FTC. Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. Morning urine and plasma samples will be collected starting the day the last is given (1 hour later) and every day thereafter for 9 days (total of 10 days of sample collection). This will allow for the assessment of the length of time TFV can be measured in the urine after last dose is taken (the "lookback" period) in the context of consistent adherence, as well as to determine how many days a patient has been off drug if a urine specimen has no detectable TFV. A correction analysis similar to that below will also be assessed in this cohort.

1b) To determine how long TFV is excreted in the urine in patients who have taken one dose of TAF/FTC. Ten healthy subjects will be given one dose of TAF/FTC under direct observation to ensure adherence. Morning urine and plasma samples will be collected starting the day the dose is given (1 hour later) and every day thereafter for 6 days (total of 7 days of sample collection). This will allow for the assessment of the length of time TFV can be measured in the urine after last dose is taken (the "lookback" period) in the context of inconsistent or intermittent (1 day only) adherence, as well as to determine how many days a patient has been off drug if a urine specimen has no detectable TFV. Investigators will also examine the correct urine TFV values for inter-subject variability by assessing which measure (specific gravity, urine creatinine, pH) will maximize the correlation between urine TFV levels and an ideal line of elimination.

Secondary Objective:

To determine the expected urine tenofovir levels in a population of HIV-positive patients on TAF-based regimens. A cross-sectional analysis of ten HIV-positive patients with undetectable viral loads on a TAF-based single tablet HIV regimen will be conducted. Morning urine and plasma samples will be collected at one time point to determine urine TFV concentration in the setting of steady state dosing in HIV patients with presumably very good adherence to medication, and compared to a historical cohort of patients on TDF-based regimens.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 1a) Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. 1b) Ten healthy subjects will be given one daily dose of TAF/FTC under direct observation to ensure adherence. Morning (not first morning) urine and plasma samples will be collected starting the day the dose is given (1 hr post-dose) and every day thereafter for 6 days. 2) Ten HIV-positive patients who have had undetectable viral loads for greater than 12 weeks (and a recent undetectable viral load in the previous 4 weeks) on an antiretroviral regimen containing TAF/FTC (i.e. Genvoya™, Odefsey™, or Descovy™ in combination with another HIV medication or medications) will have one-time pre-dose urine (early morning) and plasma samples drawn for tenofovir (TFV) concentration, as well as a comprehensive metabolic panel for measurement of creatinine clearance.1a) Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. 1b) Ten healthy subjects will be given one daily dose of TAF/FTC under direct observation to ensure adherence. Morning (not first morning) urine and plasma samples will be collected starting the day the dose is given (1 hr post-dose) and every day thereafter for 6 days. 2) Ten HIV-positive patients who have had undetectable viral loads for greater than 12 weeks (and a recent undetectable viral load in the previous 4 weeks) on an antiretroviral regimen containing TAF/FTC (i.e. Genvoya™, Odefsey™, or Descovy™ in combination with another HIV medication or medications) will have one-time pre-dose urine (early morning) and plasma samples drawn for tenofovir (TFV) concentration, as well as a comprehensive metabolic panel for measurement of creatinine clearance.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Validation of a Urine Assay to Measure Tenofovir Levels in Patients Taking Tenofovir Alafenamide
• Actual Study Start Date: Nov 16, 2017
• Actual Primary Completion Date: Mar 29, 2018
• Actual Study Completion Date: May 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1a Age 18 or older at the time of signed informed consent Not currently taking commercial FTC/TDF for PrEP or any other investigational, oral medication for the purpose of HIV PrEP Willing and able to independently provide written informed consent Tests HIV negative at time of screening using rapid HIV antibody test or serum antibody/antigen 4th generation HIV test	Drug: FTC/TAF; Participants in cohorts 1a&b will be administered FTC/TAF for 1 to 7 consecutive days and then be followed clinically for 6 to 14 days. Cohort 2 will participate in a 1 time blood and urine collection.
Experimental: Cohort 1b Age 18 or older at the time of signed informed consent Not currently taking commercial FTC/TDF for PrEP or any other investigational, oral medication for the purpose of HIV PrEP Willing and able to independently provide written informed consent Tests HIV negative at time of screening using rapid HIV antibody test or serum antibody/antigen 4th generation HIV test	Drug: FTC/TAF; Participants in cohorts 1a&b will be administered FTC/TAF for 1 to 7 consecutive days and then be followed clinically for 6 to 14 days. Cohort 2 will participate in a 1 time blood and urine collection.
Active Comparator: Cohort 2 Age 18 or older at the time of signed informed consent Willing and able to independently provide written informed consent Last viral load < 20 copies/mL within the last four weeks of screening Must be on combination antiretroviral therapy that includes TAF/FTC for at least 6 months Undetectable viral load, as defined by < 50 copies/ml, for at least 6 months	Drug: FTC/TAF; Participants in cohorts 1a&b will be administered FTC/TAF for 1 to 7 consecutive days and then be followed clinically for 6 to 14 days. Cohort 2 will participate in a 1 time blood and urine collection.

Outcome Measures

Primary Outcome Measures

1. Percentage of Urine Samples Containing TFV in Concentrations Greater Than or Equal to 1000ng/mL From the 7-dose Cohort (1b). [Daily for a maximum of 10 days]

   Cohort 1b: To determine how long TFV is excreted in the urine in patients at steady state of TAF/FTC. Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. Morning urine samples will be collected starting the day the last is given (1 hour later) and every day thereafter for 9 days (total of 10 days). Urine samples collected from all participants were analyzed via LC-MS/MS for tenofovir concentrations.

2. Percent of Urine Samples Containing TFV Levels Greater Than or Equal to 1000ng/mL in the Single Dose Cohort (1a). [7 days]

   To determine how long TFV is excreted in the urine in patients who have taken one dose of TAF/FTC. Ten healthy subjects will be given one dose of TAF/FTC under direct observation to ensure adherence. Morning urine samples will be collected starting the day the dose is given (1 hour later) and every day thereafter for 6 days (total of 7 days of sample collection). This will allow for the assessment of the length of time TFV can be measured in the urine after last dose is taken (the "lookback" period) in the context of inconsistent or intermittent (1 day only) adherence, as well as to determine how many days a patient has been off drug if a urine specimen has no detectable TFV.

3. Percentage of Urine Samples Containing Tenofovir at Concentrations Greater Than or Equal to 1000ng/mL (Cohort 2). [1 day]

   To determine the expected urine tenofovir levels in a population of patients living with HIV on TAF-based regimens. A cross-sectional analysis of ten patients living with HIV with undetectable viral loads on a TAF-based single tablet HIV regimen will be conducted. Morning urine samples will be collected at one time point to determine urine TFV concentration in the setting of steady state dosing in HIV patients with presumably very good adherence to medication.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Cohort 1(a & b) Inclusion Criteria:

• Age 18 or older at the time of signed informed consent

• Not currently taking commercial Truvada for PrEP or any other investigational, oral medication for the purpose of HIV PrEP

• Willing and able to independently provide written informed consent

• Tests HIV negative at time of screening using rapid HIV antibody test or serum antibody/antigen 4th generation HIV test

Cohort 1(a & b) Exclusion Criteria:

• Evidence of acute or chronic hepatitis B infection at the time of screening

• Other clinically significant acute or chronic medical condition, including severe infections requiring treatment such as tuberculosis, as determined by the study investigator

• Evidence of renal dysfunction (Creatinine Clearance < 30 ml/min) at the time of screening; Use Cockroft-Gault equation: GFR = (140-Age in years) x (Weight in kg) / (72 x serum creatinine)

• History of bone fractures not explained by trauma

• Grade 3 laboratory abnormality on screening tests/assessments as defined by the DAIDS grading system

• Known allergy/sensitivity to the study drug or its components

• Experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)

• Any other clinical condition or prior therapy that, in the opinion of the Principal Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

Cohort 2 Inclusion Criteria:

• Age 18 or older at the time of signed informed consent

• Willing and able to independently provide written informed consent

• Last viral load < 20 copies/mL within the last four weeks of screening

• Must be on combination antiretroviral therapy that includes TAF/FTC for at least 6 months

• Undetectable viral load, as defined by < 50 copies/ml, for at least 6 months

Cohort 2 Exclusion Criteria:

• Other clinically significant acute or chronic medical condition, including severe infections requiring treatment such as tuberculosis, as determined by the study investigator

• Evidence of renal dysfunction (Creatinine Clearance < 30 ml/min) at the time of screening; Use Cockroft-Gault equation: GFR = (140-Age in years) x (Weight in kg) / (72 x serum creatinine)

• Grade 3 laboratory abnormality on screening tests/assessments as defined by the DAIDS grading system

• Experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)

• Any other clinical condition or prior therapy that, in the opinion of the Principal Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Philadelphia FIGHT	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Philadelphia Fight
• Gilead Sciences

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 27, 2017

More Information

Publications

None provided.

• Responsible Party: Philadelphia Fight
• ClinicalTrials.gov Identifier: NCT03350672
• Other Study ID Numbers: PhiladelphiaFight
• First Posted: Nov 22, 2017
• Last Update Posted: Sep 30, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Philadelphia Fight: HIV prevention; PrEP; Descovy

Study Results

Participant Flow

Arm/Group Title	Cohort 2	Cohort 1a	Cohort 1b
Arm/Group Description	Person living with HIV, currently prescribed an FTC/TAF based regimen, who reports recent adherence	HIV negative adults, who are not taking FTC/TDF for PrEP; given 7 consecutive, daily doses of FTC/TAF	HIV negative adults, who are not currently taking FTC/TDF for PrEP; administered single dose of FTC/TAF
Period Title: Overall Study
STARTED	17	10	10
COMPLETED	10	10	10
NOT COMPLETED	7	0	0

Baseline Characteristics

Arm/Group Title	Cohort 2	Cohort 1b	Cohort 1a	Total
Arm/Group Description	Person living with HIV, currently prescribed an FTC/TAF based regimen, who reports recent adherence	HIV negative adults, who are not currently taking FTC/TDF for PrEP; administered single dose of FTC/TAF	HIV negative adults, who are not taking FTC/TDF for PrEP; given 7 consecutive, daily doses of FTC/TAF	Total of all reporting groups
Overall Participants	10	10	10	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 80%	10 100%	10 100%	28 93.3%
>=65 years	2 20%	0 0%	0 0%	2 6.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.00 (8.88)	30.10 (6.12)	33.00 (9.12)	40.03 (14.32)
Sex: Female, Male (Count of Participants)
Female	1 10%	4 40%	3 30%	8 26.7%
Male	9 90%	6 60%	7 70%	22 73.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	0 0%	0 0%	1 3.3%
Not Hispanic or Latino	9 90%	10 100%	10 100%	29 96.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 10%	1 10%	2 6.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	4 40%	2 20%	1 10%	7 23.3%
White	6 60%	6 60%	8 80%	20 66.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 10%	0 0%	1 3.3%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	10 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Urine Samples Containing TFV in Concentrations Greater Than or Equal to 1000ng/mL From the 7-dose Cohort (1b).
Description	Cohort 1b: To determine how long TFV is excreted in the urine in patients at steady state of TAF/FTC. Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. Morning urine samples will be collected starting the day the last is given (1 hour later) and every day thereafter for 9 days (total of 10 days). Urine samples collected from all participants were analyzed via LC-MS/MS for tenofovir concentrations.
Time Frame	Daily for a maximum of 10 days

Outcome Measure Data

Analysis Population Description

10 samples were collected each day during the sampling period (1 per participant).

Arm/Group Title	Cohort 1b
Arm/Group Description	HIV negative adults, who are not taking FTC/TDF for PrEP; given 7 consecutive, daily doses of FTC/TAF
Measure Participants	10
Measure urine samples	100
Day 0 post dosing	100
Day 1 post dosing	80
Day 2 post dosing	80
Day 3 post dosing	80
Day 4 post dosing	30
Day 5 post dosing	30
Day 6 post dosing	20
Day 7 post dosing	20
Day 8 post dosing	0
Day 9 post Dosing	0

2. Primary Outcome

Title	Percent of Urine Samples Containing TFV Levels Greater Than or Equal to 1000ng/mL in the Single Dose Cohort (1a).
Description	To determine how long TFV is excreted in the urine in patients who have taken one dose of TAF/FTC. Ten healthy subjects will be given one dose of TAF/FTC under direct observation to ensure adherence. Morning urine samples will be collected starting the day the dose is given (1 hour later) and every day thereafter for 6 days (total of 7 days of sample collection). This will allow for the assessment of the length of time TFV can be measured in the urine after last dose is taken (the "lookback" period) in the context of inconsistent or intermittent (1 day only) adherence, as well as to determine how many days a patient has been off drug if a urine specimen has no detectable TFV.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

10 urine samples collected on each of 7 collection days (1 per participant).

Arm/Group Title	Cohort 1a
Arm/Group Description	HIV negative adults, who are not currently taking FTC/TDF for PrEP; administered single dose of FTC/TAF
Measure Participants	10
Measure urine samples	70
Day 0 post dosng	60
Day 1 post dosing	60
Day 2 post dosing	30
Day 3 post dosing	20
Day 4 post dosing	0
Day 5 post dosing	0
Day 6 post dosing	10

3. Primary Outcome

Title	Percentage of Urine Samples Containing Tenofovir at Concentrations Greater Than or Equal to 1000ng/mL (Cohort 2).
Description	To determine the expected urine tenofovir levels in a population of patients living with HIV on TAF-based regimens. A cross-sectional analysis of ten patients living with HIV with undetectable viral loads on a TAF-based single tablet HIV regimen will be conducted. Morning urine samples will be collected at one time point to determine urine TFV concentration in the setting of steady state dosing in HIV patients with presumably very good adherence to medication.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 2
Arm/Group Description	Person living with HIV, currently prescribed an FTC/TAF based regimen, who reports recent adherence
Measure Participants	10
Measure urine samples	10
Number [percentage of urine samples]	100

Adverse Events

Time Frame	Beginning after first dose and extending through completion of the study (Cohort 1a = 7 days; Cohort 1b = 10 days; Cohort 2 = only AEs related to blood draw collected).
Arm/Group Title	Cohort 2		Cohort 1b		Cohort 1a
Arm/Group Description	Person living with HIV, currently prescribed an FTC/TAF based regimen, who reports recent adherence		HIV negative adults, who are not currently taking FTC/TDF for PrEP; administered single dose of FTC/TAF		HIV negative adults, who are not taking FTC/TDF for PrEP; given 7 consecutive, daily doses of FTC/TAF
All Cause Mortality
	Cohort 2		Cohort 1b		Cohort 1a
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Cohort 2		Cohort 1b		Cohort 1a
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 2		Cohort 1b		Cohort 1a
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/10 (10%)		0/10 (0%)
Gastrointestinal disorders
Viral gastroenteritis	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.