Clinical Trials/NCT01772823

NCT01772823

Completed

Phase 2

Project PrEPare - An Open Label Demonstration Project and Phase II Safety Study of Pre-Exposure Prophylaxis Use Among Young Men Who Have Sex With Men (YMSM) in the United States

University of North Carolina, Chapel Hill12 sites in 1 country200 target enrollmentNovember 2012

ConditionsHIV Infection

Interventions3MV Emtricitabine/tenofovir (FTC/TDF (Truvada®))PCC

DrugsEmtricitabine/tenofovir (FTC/TDF (Truvada®))

Overview

Phase: Phase 2
Intervention: 3MV
Conditions: HIV Infection
Sponsor: University of North Carolina, Chapel Hill
Enrollment: 200
Locations: 12
Primary Endpoint: Lumbar Spine Bone Mineral Density at Baseline and at Week 48
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Approximately 200 HIV-uninfected young men who have sex with men (YMSM) at high risk of acquiring HIV infection, ages 18-22 years, inclusive, will be recruited across all participating Adolescent Medicine Trials Units (AMTU). The behavioral intervention will be assigned at the level of the site, which include Many Men, Many Voices (3MV) and Personalized Cognitive Counseling (PCC). Subjects will first complete the behavioral intervention offered at their respective site and then be provided with open label emtricitabine (FTC)/tenofovir (TDF) (Truvada®) as PrEP. Behavioral and biomedical data will be collected at baseline and 0, 4, 8, 12, 24, 36 and 48 weeks. Any subjects who become HIV infected during the course of the study will be discontinued from the study agent and followed for an additional 24 weeks after the study visit at which HIV infection is confirmed. Those subjects who meet specific bone or renal criteria at the Week 48 visit or the 24-Week HIV Seropositive visit will be followed for an additional 48 weeks in the Extension Phase to monitor longer-term outcomes of potential concerns.

Detailed Description

The primary objectives of the study are to provide additional safety data regarding FTC/TDF (Truvada®) use as PrEP in YMSM, to examine acceptability, patterns of use, rates of adherence, measure levels of drug exposure and patterns of risk behavior when YMSM are provided open label FTC/TDF (Truvada®). The study will also examine information regarding safety and efficacy of FTC/TDF (Truvada®) as PrEP from prior studies.

Registry

clinicaltrials.gov

Start Date

November 2012

End Date

November 2015

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

University of North Carolina, Chapel Hill

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Willing and able to provide written informed consent;
•Male gender at birth;
•Age 18 years and 0 days through 22 years and 364 days, inclusive, at the time of signed informed consent;
•Self reports evidence of high risk for acquiring HIV infection including at least one of the following:
•At least one episode of unprotected anal intercourse with an HIV-infected male partner or a male partner of unknown HIV status during the last 6 months;
•Anal intercourse with 3 or more male sex partners during the last 6 months;
•Exchange of money, gifts, shelter, or drugs for anal sex with a male partner during the last 6 months;
•Sex with a male partner and has had a sexually transmitted infection (STI) during the last 6 months or at screening;
•Sexual partner of an HIV-infected man with whom condoms were not consistently used in the last 6 months; or
•At least one episode of anal intercourse where the condom broke or slipped off during the last 6 months;

Exclusion Criteria

•Appears visibly distraught or presence of active serious psychiatric symptoms (e.g., active hallucinations, suicidal, homicidal, or exhibiting violent behavior) at the time of consent;
•Intoxicated or under the influence of alcohol or other drugs at the time of consent;
•Any significant uncontrolled, active or chronic disease process that, in the judgment of the site investigator, would make participation in the study inappropriate. (Appropriately managed conditions, like well-controlled diabetes, would not preclude enrollment; the site is encouraged to contact the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 110 Protocol Team if they are having difficulty making the judgment.);
•History of bone fractures not explained by trauma;
•Acute or chronic hepatitis B infection as indicated by positive hepatitis B surface antigen (sAg) test at time of screening;
•Confirmed renal dysfunction (Creatinine Clearance (CrCl) \< 75 ml/min, or serum creatinine ≥ upper limit of normal (ULN), or history of renal parenchymal disease or presence of only one kidney at time of screening;
•Confirmed ≥ Grade 2 hypophosphatemia at time of screening;
•Confirmed ≥ Grade 2 hematologic system abnormality (White Blood Count (WBC), Absolute Neutrophil Count (ANC), hemoglobin, or platelets) at time of screening;
•Confirmed ≥ Grade 2 hepatobiliary system abnormality (Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), or bilirubin) at time of screening;
•Confirmed proteinuria as indicated by urine dipstick result ≥ 1+ at time of screening, regardless of urine protein to creatinine ratio(UP/C);

Arms & Interventions

3MV Behavioral Intervention Group

3MV Behavioral Intervention combined with open label FTC/TDF (Truvada®) as PrEP

Intervention: 3MV

3MV Behavioral Intervention Group

3MV Behavioral Intervention combined with open label FTC/TDF (Truvada®) as PrEP

Intervention: Emtricitabine/tenofovir (FTC/TDF (Truvada®))

PCC Behavioral Intervention Group

PCC Behavioral Intervention combined with open label FTC/TDF (Truvada®) as PrEP

Intervention: PCC

PCC Behavioral Intervention Group

PCC Behavioral Intervention combined with open label FTC/TDF (Truvada®) as PrEP

Intervention: Emtricitabine/tenofovir (FTC/TDF (Truvada®))

Outcomes

Primary Outcomes

Lumbar Spine Bone Mineral Density at Baseline and at Week 48

Time Frame: Baseline, Week 48

This outcome addresses the objective: Additional Safety Data Regarding FTC/TDF (Truvada®) Use Among HIV-uninfected YMSM. Bone mineral density at Baseline and Week 48: data reported below for lumbar spine.

Number of Participants With Unprotected Sex Acts

Time Frame: Baseline and 48 weeks

This outcome addresses the objective "Additional Safety Data Regarding FTC/TDF (Truvada®) Use Among HIV-uninfected YMSM," specifically behavioral disinhibition/risk compensation endpoints. Responses to the participant ACASI question referring to male partners in the past month/since the last survey: "Of these males (male partners), how many did you have unprotected oral or anal sex with in the last month?" (Baseline), or "Of these males (male partners), how many did you have unprotected oral or anal sex with since the last time you took this survey?" (Week 48) An event is defined as an answer of greater than 0.

Acceptability of PrEP: Distribution of Participant Feelings About Taking the Pill Every Day

Time Frame: Week 12

This outcome addresses the objective: "Acceptability when YMSM are provided open label FTC/TDF (Truvada®) and information regarding the safety and efficacy of PrEP from prior studies." Acceptability of PrEP as measured by the acceptability assessment that includes questions on usability of PrEP, user-friendliness of the medication regimen, including an assessment of side effects and delivery format, and acceptability of behavioral intervention sessions. This specific outcome focuses on the question of how participants felt about taking the pill every day.

Acceptability of PrEP: Distribution of Participant Feelings About Taking Part in the Study

Time Frame: Week 12

This outcome addresses the objective "Acceptability when YMSM are provided open label FTC/TDF (Truvada®) and information regarding the safety and efficacy of PrEP from prior studies." Acceptability of PrEP as measured by the acceptability assessment that includes questions on usability of PrEP, user-friendliness of the medication regimen, including an assessment of side effects and delivery format, and acceptability of behavioral intervention sessions. This specific outcome focuses on the question of how participants felt about taking part in the study.

Femoral Neck Bone Mineral Density at Baseline and at Week 48

Time Frame: Baseline, Week 48

Total Hip Bone Mineral Density at Baseline and at Week 48

Time Frame: Baseline, Week 48

Acceptability of PrEP: Distribution of Participant Feelings About Color of the Pill

Time Frame: Week 12

This outcome addresses the objective: "Acceptability when YMSM are provided open label FTC/TDF (Truvada®) and information regarding the safety and efficacy of PrEP from prior studies" Acceptability of PrEP as measured by the acceptability assessment that includes questions on usability of PrEP, user-friendliness of the medication regimen, including an assessment of side effects and delivery format, and acceptability of behavioral intervention sessions. This specific outcome focuses on the question of how participants felt about the color of the pill.

Measured Levels of Drug Exposure (DBS RBC FTC-TP) When YMSM Are Provided Open Label FTC/TDF (Truvada®)

Time Frame: Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

PrEP medication levels were assessed via dried blood spot (DBS) collected at each visit to quantify intracellular FTC-triphosphate concentrations.

Number of Participants With Serum Creatinine Event of Grade 1 or Higher

Time Frame: 48 Weeks

This measure addresses the objective: Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM Serum creatinine was tested at every study visit (Baseline through Week 48). The number of participants with a serum creatinine laboratory toxicity of Grade 1 or higher was assessed. Grade 1 (Mild) toxicity was defined as: 1.1 - 1.3 x ULN, where ULN is the Upper limit of normal.

Total Body Bone Mineral Density at Baseline and at Week 48

Time Frame: Baseline, Week 48

Acceptability of PrEP: Distribution of Participant Feelings About Questions About Sexual Behavior

Time Frame: Week 12

This outcome addresses the objective: Acceptability When YMSM Are Provided Open Label FTC/TDF (Truvada®) and Information Regarding the Safety and Efficacy of PrEP From Prior Studies. Acceptability of PrEP as measured by the acceptability assessment that includes questions on usability of PrEP, user-friendliness of the medication regimen, including an assessment of side effects and delivery format, and acceptability of behavioral intervention sessions. This question reports on how the participants felt about being asked questions about sexual behavior at every visit

Number of Participants With Decrease in Absolute Bone Mineral Density (BMD) From Baseline to Week 48

Time Frame: 48 weeks

This outcome addresses the objective "Additional Safety Data Regarding FTC/TDF (Truvada®) Use Among HIV-uninfected YMSM." The total number of participants with dual-energy radiography absorptiometry scanning (DXA) data through Week 48 who experienced varying degrees of decrease in absolute BMD in at least one region (spine, hip, or whole body) between Baseline and Week 48.

Acceptability of PrEP: Distribution of Participant Feelings About Taste of the Pill

Time Frame: Week 12

This outcome addresses the objective: "Acceptability when YMSM are provided open label FTC/TDF (Truvada®) and information regarding the safety and efficacy of PrEP from prior studies" Acceptability of PrEP as measured by the acceptability assessment that includes questions on usability of PrEP, user-friendliness of the medication regimen, including an assessment of side effects and delivery format, and acceptability of behavioral intervention sessions. This specific outcome focuses on the question of how participants felt about the taste of the pill.

Acceptability of PrEP: Distribution of Participant Feelings About Physician Exam

Time Frame: Week 12

Number of Sex Partners

Time Frame: Baseline and 48 weeks

This outcome addresses the objective "Additional Safety Data Regarding FTC/TDF (Truvada®) Use Among HIV-uninfected YMSM," specifically behavioral disinhibition/risk compensation endpoints. Responses to the participant ACASI question referring to number of male partners in the past month/since the last survey: "During the past month, how many male partners have you had sexual contact with (oral or anal)?" (Baseline), or "Since the last time you took this survey, how many male partners have you had sexual contact with (oral or anal)?" (Week 48) And responses to the participant ACASI question referring to number of HIV-positive male partners in the past month/since the last survey: "Of those you had unprotected sex with, how many did you know were HIV positive?"

Acceptability of PrEP: Distribution of Participant Feelings About Size of the Pill

Time Frame: Week 12

Acceptability of PrEP: Distribution of Participant Feelings About Risk Reduction Counseling at Every Visit

Time Frame: Week 12

This outcome addresses the objective: Acceptability When YMSM Are Provided Open Label FTC/TDF (Truvada®) and Information Regarding the Safety and Efficacy of PrEP From Prior Studies. Acceptability of PrEP as measured by the acceptability assessment that includes questions on usability of PrEP, user-friendliness of the medication regimen, including an assessment of side effects and delivery format, and acceptability of behavioral intervention sessions. This question reports on how the participants felt about having individual risk reduction counseling at every visit

Patterns of Use, Rates of Adherence and Measured Levels of Open Label FTC/TDF (Truvada®) Drug Exposure

Time Frame: Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

This outcome addresses the objective: "Patterns of Use, Rates of Adherence and Measured Levels of Drug Exposure When YMSM Are Provided Open Label FTC/TDF (Truvada®) and Information Regarding the Safety and Efficacy of PrEP From Prior Studies." PrEP medication levels were assessed via dried blood spot (DBS) collected at each visit to quantify intracellular TFV-DP and FTC-triphosphate concentrations. DBS results were translated into dosing categories previously used in PrEP trials with adult MSM. Dosing categories included below lower limit of quantitation (BLQ), lower limit of quantitation to 349 fmol per punch (fewer than 2 tablets per week), 350- 699 fmol per punch (2-3 tablets per week), 700-1250 fmol per punch (4 tablets per week), and \>1250 fmol per punch (daily).

Acceptability of PrEP: Distribution of Participant Feelings About HIV Test at Every Visit

Time Frame: Week 12

Measured Levels of Drug Exposure (DBS RBC TFV-DP) When YMSM Are Provided Open Label FTC/TDF (Truvada®)

Time Frame: Week 4, Week 8, Week 12, Week 24, Week 36, Week 48

This outcome addresses the objective: "Measured Levels of Drug Exposure (DBS RBC TFV-DP) When YMSM Are Provided Open Label FTC/TDF (Truvada®) and Information Regarding the Safety and Efficacy of PrEP From Prior Studies." PrEP medication levels were assessed via dried blood spot (DBS) collected at each visit to quantify intracellular TFV-DP concentrations.

Secondary Outcomes

Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 8 of 10: "The Workshop/Session Was Enjoyable."(48 weeks)
Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 5 of 10: "The Topic of This Workshop/Session Was Interesting."(48 weeks)
Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 7 of 10: "The Topic of This Workshop/Session Was Relevant to my Life."(48 weeks)
Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Age)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 1: Away From Home)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 7: Routine Change)(48 weeks)
Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 1 of 10: "I Learned a Lot From This Workshop/Session."(48 weeks)
Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 2 of 10: "I Will be Able to Apply What I Learned From This Workshop/Session in my Life."(48 weeks)
Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 3 of 10: "I Was Given an Opportunity to Participate and Discuss Information With Others."(48 weeks)
Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 4 of 10: "The Workshop/Session Was Well Organized."(48 weeks)
Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 10 of 10: "I Felt Comfortable Participating in This Workshop/Session."(48 weeks)
Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Race, 5 Categories)(48 weeks)
Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Race, 2 Categories)(48 weeks)
Acceptability and Feasibility of Text Message Reminders: Number Using Text Messaging Reminders(48 weeks)
Acceptability and Feasibility of Text Message Reminders: Number Discontinuing Text Messaging Reminders(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 4: Too Many Pills)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 8: Study Pill Harmful)(48 weeks)
Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 6 of 10: "The Presenter(s) Stimulated my Interest in the Material."(48 weeks)
Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (BMI, Categorical)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 9: Fell Asleep)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 10: Felt Ill)(48 weeks)
Explore Potential Demographic and/or Behavioral Differences Between Youth Who Are Interested in Participating in a PrEP Study Versus Those Who Are Not. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared.(48 weeks)
Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Log 10 Viral Load)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 11: Felt Depressed)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 13: No Risky Sex)(48 weeks)
Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation. Item 9 of 10: "I Would Recommend This Workshop/Session to Others."(48 weeks)
Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Ethnicity, Hispanic vs. Non-Hispanic or Latino)(48 weeks)
Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (High Risk Sex Acts)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 2: Busy With Other Things)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 3: Simply Forgot)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 5: Side Effects)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 6: Others Notice)(48 weeks)
Acceptability and Feasibility of Text Message Reminders as Measured by Subject Rating of the Reasons for Missing Medications on a 4-point Likert Scale. (Question 12: Ran Out of Pills)(48 weeks)