Protocol HVTN 505: Phase 2b, randomized, placebo-controlled test-of-concept trial to evaluate the safety and efficacy of a multiclade HIV-1 DNA plasmid vaccine followed by a multiclade HIV-1 recombinant adenoviral vector vaccine in HIV-uninfected, adenovirus type 5 neutralizing antibody negative, circumcised men and male-to-female (MTF) transgender persons, who have sex with men

Study ID
STU 032011-074

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

Contact
Tianna Petersen
214-590-0611
tianna.petersen@utsouthwestern.edu

Principal Investigator
Mamta Jain

Summary

This study is a multicenter, randomized, placebo-controlled, double-blind trial. a total of approximately 2,500 subjects nationwide and 100 subjects locally will be enrolled into this study (350 will be screened). The study will consist of 18 clinical visits in which subjects will have blood drawn in order to have labs processed. Patients will be randomized into 1 of 2 different treatment arms:

arm 1: 1 injection of the Dna vaccine 3 times during the first 2 months and 1 injection of the rad5 vaccine 1 time during your Month 6 visit

arm 2: 4 injections of the placebo 4 times during your 4 scheduled visits

Primary endpoint 1: HiV-1 infection diagnosed at or after Day 196 post-enrollment through the Month 24 visit

Primary endpoint 2: VL setpoint defined as the average of all log10 plasma HiV-1 Rna values obtained at the Week 10 through Week 20 study visits after the diagnosis of HiV infection and prior to aRT initiation, for HiV-infected participants who are diagnosed at or after Day 196 through the Month 24 study visit



as per Version 6 of the protocol, the endpoints have changed:

Primary endpoint 1: HiV-1 infection diagnosed after Day 0 through the Month 24 visit

Primary endpoint 2: HiV-1 infection diagnosed after Day 0 including all available follow up through the maximum Month 48 visit


also, all participants enrolled under versions 1 through 4 of the protocol will continue to be followed. in addition, the participants who terminated the study early or who completed the primary 24 month follow up specified under version 4 will be invited back into the study. This choice ensures that the primary endpoints are estimated with maximal precision.

Participant Eligibility


* Male, age 18 to 50 years, who is fully circumcised (as documented at screening examination) and who, in the 6 months prior to randomization, experienced 1 or both of the following HIV risk criteria:
unprotected anal intercourse with 1 or more male or MTF transgender partner(s);
or
anal intercourse with 2 or more male or MTF transgender partners.

Note: Volunteers who have been in a monogamous relationship with an HIV-1
seronegative partner for > 1 year are excluded.


* Negative HIV-1 and -2 blood test (FDA-approved enzyme immunoassay [EIA])

* Ad5 nAb titer < 1:18

* ALT <= 2.5 upper limit of normal

* Within reach of a participating study site and willing to be followed for the planned duration of the study, including long-term safety surveillance contact for 5 years after enrollment

* Able and willing to provide informed consent

* Assessment of understanding: demonstrates understanding of this study and the Step Study results; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly

* Willing to receive HIV test results

* Willing to discuss HIV infection risks and amenable to risk reduction counseling

* Good general health as shown by medical history, physical exam, and screening laboratory tests

* Agrees not to enroll in another study of an investigational research agent prior to unblinding of the HVTN 505 study