Clinical trial NCT01772823: An Open Label Demonstration Project and Phase II Safety Study of Pre-Exposure Prophylaxis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infection
Keywords: HIV, PrEP, FTC/TDF, Truvada®
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute of Mental Health (NIMH)
First posted: 2013-01-21
Enrollment: 200
Sex: MALE
Minimum age (years): 18
Maximum age (years): 22
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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;
* Tests HIV antibody negative at time of screening;
* Willing to provide locator information to study staff;
* Willing to take pre-exposure prophylaxis (PrEP);
* Willing to participate in behavioral intervention;
* Reports intention not to relocate out of the Adolescent Medicine Trial Unit (AMTU) study area during the course of the study; and
* Does not have a job or other obligations that would require long absences from the AMTU study area (greater than 4 weeks at a time).

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);
* UP/C \> 0.37 g/g at time of screening, regardless of urine dipstick protein result;
* Confirmed normoglycemic glucosuria as indicated by urine dipstick result ≥ 1+ in the presence of normal serum glucose (\<120 mg/dL) at time of screening;
* A confirmed Grade ≥ 3 toxicity on any screening evaluations;
* Known allergy/sensitivity to the study agent or its components;
* Concurrent participation in an HIV vaccine study or other investigational drug study, including oral or topical PrEP (microbicide) studies;
* Use of disallowed medications ; or
* Inability to understand spoken English.

Primary outcomes:
measure: Number of Participants With Serum Creatinine Event of Grade 1 or Higher
timeFrame: 48 Weeks
measure: Number of Participants With Decrease in Absolute Bone Mineral Density (BMD) From Baseline to Week 48
timeFrame: 48 weeks
measure: Lumbar Spine Bone Mineral Density at Baseline and at Week 48
timeFrame: Baseline, Week 48
measure: Femoral Neck Bone Mineral Density at Baseline and at Week 48
timeFrame: Baseline, Week 48
measure: Total Body Bone Mineral Density at Baseline and at Week 48
timeFrame: Baseline, Week 48
measure: Total Hip Bone Mineral Density at Baseline and at Week 48
timeFrame: Baseline, Week 48
measure: Number of Participants With Unprotected Sex Acts
timeFrame: Baseline and 48 weeks
measure: Number of Sex Partners
timeFrame: Baseline and 48 weeks
measure: Acceptability of PrEP: Distribution of Participant Feelings About Size of the Pill
timeFrame: Week 12
measure: Acceptability of PrEP: Distribution of Participant Feelings About Taste of the Pill
timeFrame: Week 12
measure: Acceptability of PrEP: Distribution of Participant Feelings About Color of the Pill
timeFrame: Week 12
measure: Acceptability of PrEP: Distribution of Participant Feelings About Taking the Pill Every Day
timeFrame: Week 12
measure: Acceptability of PrEP: Distribution of Participant Feelings About Taking Part in the Study
timeFrame: Week 12
measure: Acceptability of PrEP: Distribution of Participant Feelings About HIV Test at Every Visit
timeFrame: Week 12
measure: Acceptability of PrEP: Distribution of Participant Feelings About Risk Reduction Counseling at Every Visit
timeFrame: Week 12
measure: Acceptability of PrEP: Distribution of Participant Feelings About Questions About Sexual Behavior
timeFrame: Week 12
measure: Acceptability of PrEP: Distribution of Participant Feelings About Physician Exam
timeFrame: Week 12
measure: Patterns of Use, Rates of Adherence and Measured Levels of Open Label FTC/TDF (Truvada®) Drug Exposure
timeFrame: Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Measured Levels of Drug Exposure (DBS RBC FTC-TP) When YMSM Are Provided Open Label FTC/TDF (Truvada®)
timeFrame: Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Measured Levels of Drug Exposure (DBS RBC TFV-DP) When YMSM Are Provided Open Label FTC/TDF (Truvada®)
timeFrame: Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
Secondary outcomes:
measure: 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."
timeFrame: 48 weeks
measure: 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."
timeFrame: 48 weeks
measure: 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."
timeFrame: 48 weeks
measure: 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."
timeFrame: 48 weeks
measure: 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."
timeFrame: 48 weeks
measure: 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."
timeFrame: 48 weeks
measure: 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."
timeFrame: 48 weeks
measure: 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."
timeFrame: 48 weeks
measure: 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."
timeFrame: 48 weeks
measure: 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."
timeFrame: 48 weeks
measure: Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Age)
timeFrame: 48 weeks
measure: 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.
timeFrame: 48 weeks
measure: Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Race, 5 Categories)
timeFrame: 48 weeks
measure: Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Race, 2 Categories)
timeFrame: 48 weeks
measure: Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Ethnicity, Hispanic vs. Non-Hispanic or Latino)
timeFrame: 48 weeks
measure: Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (BMI, Categorical)
timeFrame: 48 weeks
measure: Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (Log 10 Viral Load)
timeFrame: 48 weeks
measure: Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared. (High Risk Sex Acts)
timeFrame: 48 weeks
measure: Acceptability and Feasibility of Text Message Reminders: Number Using Text Messaging Reminders
timeFrame: 48 weeks
measure: Acceptability and Feasibility of Text Message Reminders: Number Discontinuing Text Messaging Reminders
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
measure: 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)
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Aurora
country: United States
facility: University of Colorado - The Children's Hospital of Denver
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Stroger Hospital and the CORE Center
state: Illinois
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Fenway Institute
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Childrens Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Cook County Health & Hospitals System
name: Sybil Hosek, PhD
role: STUDY_CHAIR
References:
citation: Havens PL, Perumean-Chaney SE, Patki A, Cofield SS, Wilson CM, Liu N, Anderson PL, Landovitz RJ, Kapogiannis BG, Hosek SG, Mulligan K. Changes in Bone Mass After Discontinuation of Preexposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine in Young Men Who Have Sex With Men: Extension Phase Results of Adolescent Trials Network Protocols 110 and 113. Clin Infect Dis. 2020 Feb 3;70(4):687-691. doi: 10.1093/cid/ciz486.
citation: Castillo-Mancilla J, Seifert S, Campbell K, Coleman S, McAllister K, Zheng JH, Gardner EM, Liu A, Glidden DV, Grant R, Hosek S, Wilson CM, Bushman LR, MaWhinney S, Anderson PL. Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6692-6697. doi: 10.1128/AAC.01017-16. Print 2016 Nov.