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)

NCT01769456 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ATN 113 Version 2.0
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 6

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.

Conditions

HIV Infection

Keywords

HIV, PrEP, FTC/TDF, Truvada®

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Serum Creatinine Event of Grade 1 or Higher Over the Course of the Study

  This represents one of the indicators associated with the objective: Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM. Participants were assessed for any serum creatinine event of Grade 1 or higher over the course of the study (Week 0 through Week 48).

  48 weeks

• Lumbar Spine Bone Mineral Density: Percent Change From Baseline to Week 48

  The percent change in lumbar spine BMD from baseline measurement to Week 48 is calculated as: Percent change= \[(Value at Week 48 - Value at Baseline)/(Value at Baseline)\] x 100 This represents one of the indicators associated with the objective: Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM.

  Baseline, Week 48

• Femoral Neck Bone Mineral Density: Percent Change From Baseline to Week 48

  The percent change in femoral neck BMD from baseline measurement to Week 48 is calculated as: Percent change= \[(Value at Week 48 - Value at Baseline)/(Value at Baseline)\] x 100 This represents one of the indicators associated with the objective: Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM.

  Baseline, Week 48

• Total Body Bone Mineral Density: Percent Change From Baseline to Week 48

  The percent change in total body BMD from baseline measurement to Week 48 is calculated as: Percent change= \[(Value at Week 48 - Value at Baseline)/(Value at Baseline)\] x 100 This represents one of the indicators associated with the objective: Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM.

  Baseline, Week 48

• Total Hip Bone Mineral Density: Percent Change From Baseline to Week 48

  The percent change in total hip BMD from baseline measurement to Week 48 is calculated as: Percent change= \[(Value at Week 48 - Value at Baseline)/(Value at Baseline)\] x 100 This represents one of the indicators associated with the objective: Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM.

  Baseline, Week 48

• Number of Participants With Decrease in Bone Mineral Density

  The proportion of subjects with DXA data through Week 48 who experienced varying degrees of decrease in absolute BMD in at least one region (spine, hip, or whole body). This represents one of the indicators associated with the objective: Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM.

  48 weeks

• Behavioral Disinhibition/Risk Compensation: Number of Participants Reporting Unprotected Sex

  Behavioral disinhibition/risk compensation was assessed based on a number of questions, including the following related to unprotected sex from the participant ACASI: "Of these males \[male partners\], how many did you have unprotected oral or anal sex with since the last time you took this survey?" An event is defined as an answer of greater than 0. This represents one of the indicators associated with the objective: Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM.

  Week 48

• Behavioral Disinhibition/Risk Compensation: Number of Male Sexual Partners

  Behavioral disinhibition/risk compensation was assessed based on a number of questions, including the following related to related to number of male sexual partners from the participant ACASI: "Since the last time you took this survey, how many male partners have you had sexual contact with (oral or anal)?" This represents one of the indicators associated with the objective: Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM.

  Week 48

• Acceptability of PrEP Regimen and Study Visits

  This represents one of the indicators associated with 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.

  Week 12

• Estimation of Medication Adherence by Dried Blood Spot (DBS) Results

  This outcome addresses the objective: 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. Medication adherence is estimated by factors including levels of drug exposure as measured by DBS red blood cell (RBC) samples. The TFV dosing level was translated into number of dosing days per week for week 8 onwards using lab estimates as follows: '\<2 days' is defined as \<350 (fmol/punch), '2 days' as 350 to 700 (fmol/punch), '4 days' as \>700 to 1250 (fmol/punch), and 'Daily' as \>1250 (fmol/punch). The TFV dosing level was translated into number of dosing days for week 4 using lab estimates as follows: '\<2 days' is defined as \<275 (fmol/punch), '2 days' as 275 to 525 (fmol/punch), '4 days' as \>525 to 950 (fmol/punch),and 'Daily' as \>950 (fmol/punch)

  Week 4, Week 12, Week 24, Week 36, Week 48

Secondary Outcomes (6)

• Acceptability and Feasibility of Two Types of Efficacious Sexual Risk Reduction Interventions as Measured by Session Evaluation

  48 weeks

• Number of Participants Using Text Messaging Reminders

  Baseline through Week 48

• Rating of the Reasons for Missing Medications on a 4-point Likert Scale.

  48 weeks

• Demographic and/or Behavioral Difference Between Study Groups. Behavioral Disinhibition/Risk Compensation Endpoints Will be Compared.

  48 weeks

• Evaluation of the Process of Protocol Implementation

  48 weeks

Study Arms (1)

PCC Behavioral Intervention Group

EXPERIMENTAL

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

Behavioral: PCC; Drug: Emtricitabine/tenofovir (FTC/TDF (Truvada®))

Interventions

PCC BEHAVIORAL

Personalized Cognitive Counseling (PCC) is based on the Model of Relapse Prevention and Gold's Self-Appraisal of Risk Behavior. PCC is a 1-hour, single-session, individual level intervention administered by a trained counselor in a clinic setting. Counselors ask the client to recall and describe a recent encounter of unprotected anal sex with another man of unknown or sero-discordant HIV status. The client then identifies and expresses thoughts, feelings, or attitudes that might have led to the high-risk behavior. The client and counselor examine and identify thoughts that may have led the client to decide to engage in high transmission risk sex. The client and counselor agree on strategies that can be used to deal with similar situations in the future.

Also known as: Personalized Cognitive Counseling

PCC Behavioral Intervention Group

Emtricitabine/tenofovir (FTC/TDF (Truvada®)) DRUG

All subjects will be provided with daily FTC/TDF (Truvada®) as Pre-exposure prophylaxis (PrEP) for 48 weeks.

Also known as: FTC/TDF, Truvada®, Emtricitabine/tenofovir, PrEP

PCC Behavioral Intervention Group

Eligibility Criteria

• Age: 15 Years - 17 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Gilead Sciences: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (6)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of Colorado - The Children's Hospital of Denver

Aurora, Colorado, 80045, United States

Location

Stroger Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

Fenway Institute

Boston, Massachusetts, 02215, United States

Location

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• 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.

  PMID: 28873128 RESULT

• 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.

  PMID: 31179503 DERIVED

Related Links

• ATN website

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine; Tenofovir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Bob Harris
• Organization: Westat

bobharris@westat.com

301-251-1500

Study Officials

• Sybil Hosek, PhD

  Stroger Hospital of Cook County

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2013
• First Posted: January 16, 2013
• Study Start: March 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2016
• Last Updated: January 17, 2018
• Results First Posted: November 13, 2017

Record last verified: 2017-11

Locations

US (6)