Clinical trial NCT01769456: An Open Label Demonstration Project and Phase II Safety Study of Pre-Exposure Prophylaxis Use Among 15 to 17 Year Old Young Men Who Have Sex With Men (YMSM)
Official title: Project PrEPare - An Open Label Demonstration Project and Phase II Safety Study of Pre-Exposure Prophylaxis Use Among 15 to 17 Year Old 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: Gilead Sciences
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-01-16
Enrollment: 78
Sex: MALE
Minimum age (years): 15
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Approximately 100 HIV-uninfected YMSM at high risk of acquiring HIV infection, between the ages of 15 and 17 inclusive will be enrolled across all participating Adolescent Medicine Trial Units (AMTUs). Subjects will complete the behavioral intervention selected by all participating sites, Personalized Cognitive Counseling (PCC), and will then be provided with open label emtricitabine (FTC)/tenofovir (TDF) (Truvada®) as pre-exposure prophylaxis (PrEP). Behavioral and biomedical data will be collected at baseline and at 0, 4, 8, 12, 24, 36 and 48 weeks. Any subject who becomes HIV infected during the course of the study will be discontinued from the study agent and be 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 aims of the study are to obtain additional data on the safety of FTC/TDF (Truvada®) and to evaluate acceptability, patterns of use, rates of adherence, and measured levels of drug exposure when YMSM are provided with open label FTC/TDF (Truvada®) and information regarding safety and efficacy of FTC/TDF (Truvada®) as PrEP based on prior studies in adults. The study will also examine patterns of sexual risk behavior among HIV-uninfected YMSM in the U.S. at high risk of acquiring HIV infection who are provided with open label FTC/TDF (Truvada®) as PrEP. The study will also explore the feasibility and acceptability of implementing an efficacious risk reduction behavioral intervention prior to the provision of PrEP- PCC. The inclusion of a behavioral intervention in this project not only addresses the ethical responsibility of providing at least the minimum risk reduction education to all subjects given the high HIV risk of the study population, but also builds behavioral skills to assist subjects in reducing their risk when not taking PrEP. Furthermore, the study will evaluate the process of protocol implementation to better understand how to best implement PrEP research and program practice at adolescent medicine sites, including an evaluation of consent procedures and the acceptability/feasibility of allowing youth minors to consent for their own participation in HIV prevention intervention, to the extent allowable by local laws and regulations, and to allow youth minor participation in a clinical trial without requiring disclosure of their sexual orientation and risk behaviors to their parents or legal guardians.

Eligibility criteria: Inclusion Criteria:

* Willing and able to provide written informed consent;
* Male gender at birth;
* Age 15 years and 0 days through 17 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 PrEP;
* Willing to participate in behavioral intervention;
* Reports intention not to relocate out of AMTU study area during the course of the study; and
* Does not have a job or other obligations that would require long absences from 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) 113 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 calculated based on bedside Schwartz formula: Glomerular filtration rate (GFR) = (0.413 x (height in centimeters)) / (serum creatinine in mg/dl)), 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 Over the Course of the Study
timeFrame: 48 weeks
measure: Lumbar Spine Bone Mineral Density: Percent Change From Baseline to Week 48
timeFrame: Baseline, Week 48
measure: Femoral Neck Bone Mineral Density: Percent Change From Baseline to Week 48
timeFrame: Baseline, Week 48
measure: Total Body Bone Mineral Density: Percent Change From Baseline to Week 48
timeFrame: Baseline, Week 48
measure: Total Hip Bone Mineral Density: Percent Change From Baseline to Week 48
timeFrame: Baseline, Week 48
measure: Number of Participants With Decrease in Bone Mineral Density
timeFrame: 48 weeks
measure: Behavioral Disinhibition/Risk Compensation: Number of Participants Reporting Unprotected Sex
timeFrame: Week 48
measure: Behavioral Disinhibition/Risk Compensation: Number of Male Sexual Partners
timeFrame: Week 48
measure: Acceptability of PrEP Regimen and Study Visits
timeFrame: Week 12
measure: Estimation of Medication Adherence by Dried Blood Spot (DBS) Results
timeFrame: Week 4, 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
timeFrame: 48 weeks
measure: Number of Participants Using Text Messaging Reminders
timeFrame: Baseline through Week 48
measure: Rating of the Reasons for Missing Medications on a 4-point Likert Scale.
timeFrame: 48 weeks
measure: Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared.
timeFrame: 48 weeks
measure: Evaluation of the Process of Protocol Implementation
timeFrame: 48 weeks
measure: Demographic and/or Behavioral Differences Between Youth Who Are Interested in Participating in a PrEP Study Versus Those Who Are Not.
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: Chicago
country: United States
facility: Stroger Hospital of Cook County
state: Illinois
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Boston
country: United States
facility: Fenway Institute
state: Massachusetts
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Stroger Hospital of Cook County
name: Sybil Hosek, PhD
role: STUDY_CHAIR
References:
citation: Hosek SG, Landovitz RJ, Kapogiannis B, Siberry GK, Rudy B, Rutledge B, Liu N, Harris DR, Mulligan K, Zimet G, Mayer KH, Anderson P, Kiser JJ, Lally M, Brothers J, Bojan K, Rooney J, Wilson CM. Safety and Feasibility of Antiretroviral Preexposure Prophylaxis for Adolescent Men Who Have Sex With Men Aged 15 to 17 Years in the United States. JAMA Pediatr. 2017 Nov 1;171(11):1063-1071. doi: 10.1001/jamapediatrics.2017.2007.
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.