Safety and Effectiveness of HIV-1 DNA Plasmid Vaccine and HIV-1 Recombinant Adenoviral Vector Vaccine in HIV-Uninfected, Circumcised Men and Male-to-Female (MTF) Transgender Persons Who Have Sex With Men

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00865566
• Other study ID #: HVTN 505
• Secondary ID: 10753
• Status: Terminated
• Phase: Phase 2
• Start date: May 2009
• Est. completion date: October 6, 2017

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and efficacy of a VRC DNA/rAd5 vaccine regimen in healthy, circumcised men and male-to-female (MTF) transgender persons who have sex with men.

NOTES:

As of April 2013, all vaccinations in this study have been stopped.

As of June 2017, this study has been closed.

Description:

In 2007, the Joint United Nations Programme on HIV/AIDS estimated that 33.2 million people were living with HIV/AIDS globally. The U.S. HIV prevalence data reported in October 2008 by the Centers for Disease Control and Prevention estimate that 1.1 million adults and adolescents were living with diagnosed or undiagnosed HIV infection in the United States at the end of 2006. Nearly half of all U.S. HIV infections (48.1%) were found in men who have sex with men (MSM). Given the difficulty of maintaining behaviors that prevent HIV transmission over a lifetime and the occurrence of nonconsensual sex, the need for a safe and effective vaccine is clear. The primary purpose of this study is to determine the safety and efficacy of a VRC DNA/rAd5 vaccine regimen in healthy, at-risk, circumcised men and MTF transgender persons who have sex with men.

Participants will be randomly assigned to one of two arms. Participants in Arm 1 will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. Participants in Arm 2 will receive placebo injections at study entry and on Days 28, 56, and 168.

Participants who do not become HIV infected will be actively followed for a minimum of 24 months and will continue to be followed by the study for long-term safety surveillance for a total of 5 years following enrollment. Participants will be contacted annually during the period of long-term safety surveillance.

Participants who are found to be HIV infected prior to receiving their first injection or who receive their first injection but were HIV infected prior to study start will be followed on a modified schedule.

Participants who become HIV infected will be followed for 6 months post-diagnosis.

At most study visits, participants will undergo a physical exam and blood draw.

NOTES:

As of April 2013, all vaccinations in this study have been stopped. Participants have been notified of whether they received the study vaccines or placebo. Participants diagnosed with HIV infection will attend study visits for 6 months for health monitoring. Participants who are not diagnosed with HIV infection will attend planned study visits for 24 months and will be followed by the study clinic at least annually for a total of 5 years following study enrollment.

As of June 2017, this study has been closed. Therefore, to avoid further burden on study participants, further participant follow-up for the study is suspended.

Other known NCT identifiers

• NCT00919789

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2504
• Est. completion date: October 6, 2017
• Est. primary completion date: October 6, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• HIV-1 and -2 negative

• Good general health

• Fully circumcised

• Experienced one or both of the following HIV risk criteria in the 6 months before study entry:

1. Unprotected anal intercourse with one or more male or MTF transgender partner(s)

2. Anal intercourse with two or more male or MTF transgender partners

• Alanine aminotransferase (ALT) 2.5 or less times the upper limit of normal (ULN)

• Ad5 neutralizing antibody (nAb) titer less than 1:18

• Have access to a participating study site and are willing to be followed during the study

• Demonstrate understanding of the study

• Willing to receive HIV test results

• Willing to discuss HIV infection risks and amenable to risk-reduction counseling

• Agrees not to enroll in another study of an investigational research agent before unblinding of this study

• NOTE: MTF transgender volunteers who have undergone gender reassignment surgery (GRS) are eligible to participate if they provide documentation from a health care provider confirming that they were fully circumcised prior to GRS. MTF transgender volunteers who have not undergone GRS are eligible to participate if they meet all enrollment criteria. Receipt of hormonal therapy does not make a transgender volunteer ineligible.

Exclusion Criteria:

• HIV vaccines in prior HIV vaccine trial. Participants who can provide documentation that they received a placebo in a prior HIV trial may be eligible.

• Used antiretroviral (ARV) drugs for the purpose of HIV-1 prophylaxis for greater than or equal to 50% of days during the 3 months prior to first vaccination or for 30 consecutive days within the 60 days prior to first vaccination

• Circumcised within 90 days prior to first vaccination or displays evidence that surgical site is not fully healed

• Immunosuppressive medications within 168 days prior to first study vaccination. Participants who have used corticosteroid nasal sprays for allergic rhinitis; topical corticosteroids for mild, uncomplicated dermatitis; or oral/parenteral corticosteroids for nonchronic conditions are not excluded.

• Blood products within 90 days prior to first study vaccination

• Immunoglobulin within 90 days prior to first study vaccination

• Live attenuated vaccines other than influenza vaccine within 30 days prior to first study vaccination

• Investigational research agents within 90 days prior to first study vaccination

• Influenza vaccine or any vaccines that are not live attenuated within 14 days prior to first study vaccination

• Allergy treatment with antigen injections within 30 days prior to first study vaccination or that are scheduled within 14 days after first vaccination

• Clinically significant medical condition, physical examination findings, abnormal laboratory results, or past medical history that, in the judgment of the investigator, has significant implications for current health

• Any medical, psychiatric, or job-related responsibility that would interfere with the study. More information about this criterion can be found in the protocol.

• Any concern that, in the opinion of the investigator, may interfere with a participant's completion of the post-vaccination symptom log

• History of serious adverse reactions to vaccinations, including anaphylaxis or allergy to any of the vaccine's components

• Current anti-tuberculosis prophylaxis or therapy

• Autoimmune disease. People with mild, stable, and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate reactogenicity and adverse event assessments are not excluded.

• Immunodeficiency

• Bleeding disorder

• History of malignancy

• Seizure disorder. People with a history of seizures who have had no seizures within the 3 years prior to study entry are not excluded.

• Asthma other than mild, well-controlled asthma

• Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic angioedema

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• DNA plasmid vaccine
4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid
• Recombinant adenoviral serotype 5 (rAD5) vector vaccine
1 x 10^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid
• DNA vaccine placebo
1 mL IM via Biojector® in either deltoid
• HIV-1 recombinant adenovirus vaccine placebo
1 mL administered IM by needle and syringe in either deltoid

Locations

Country	Name	City	State
United States	Care-Id Crs	Annandale	Virginia
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	VRC Clinical Trials Core CRS	Bethesda	Maryland
United States	Alabama CRS	Birmingham	Alabama
United States	Brigham and Women's Hospital Vaccine CRS (BWH VCRS)	Boston	Massachusetts
United States	Fenway Health (FH) CRS	Boston	Massachusetts
United States	UIC Project WISH CRS	Chicago	Illinois
United States	Case Clinical Research Site	Cleveland	Ohio
United States	University of Texas Southwestern CRS	Dallas	Texas
United States	The Hope Clinic of the Emory Vaccine Center CRS	Decatur	Georgia
United States	Baylor Vaccine Research Center CRS	Houston	Texas
United States	The AIDS Research Alliance of America CRS	Los Angeles	California
United States	UCLA CARE Center CRS	Los Angeles	California
United States	Vanderbilt Vaccine (VV) CRS	Nashville	Tennessee
United States	Columbia P&S CRS	New York	New York
United States	New York Blood Center CRS	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Orlando Immunology Center CRS	Orlando	Florida
United States	Penn Prevention CRS	Philadelphia	Pennsylvania
United States	University of Rochester Vaccines to Prevent HIV Infection CRS	Rochester	New York
United States	Bridge HIV CRS	San Francisco	California
United States	Seattle Vaccine and Prevention CRS	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	HIV Vaccine Trials Network

Country where clinical trial is conducted

United States, 

References & Publications (3)

Benmira S, Bhattacharya V, Schmid ML. An effective HIV vaccine: A combination of humoral and cellular immunity? Curr HIV Res. 2010 Sep;8(6):441-9. Review. — View Citation

Lu S. Immunogenicity of DNA vaccines in humans: it takes two to tango. Hum Vaccin. 2008 Nov-Dec;4(6):449-52. Epub 2008 Nov 28. Review. — View Citation

Patterson S, Papagatsias T, Benlahrech A. Use of adenovirus in vaccines for HIV. Handb Exp Pharmacol. 2009;(188):275-93. doi: 10.1007/978-3-540-71029-5_13. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participant Dropout Through Month 48	For participants remaining uninfected, dropout is assessed only for primary follow-up, i.e. clinic visits. Protocol versions 4 and earlier included 24 months of primary follow-up, and versions 5 and later included 48 months. Participants may terminate early after completing primary follow-up, and participants who were found to be HIV-1 infected are analyzed as non-dropouts, so the number of dropouts and number of early terminations need not match.	Enrollment through Month 48 visit
Primary	Participant Dropout Prior to Unblinding	The trial was unblinded on April 23, 2013, and the protocol was in version 4 at the time.; For participants remaining uninfected, dropout is assessed only for primary follow-up, i.e. clinic visits. Protocol versions 4 and earlier included 24 months of primary follow-up, and versions 5 and later included 48 months. Participants may terminate early after completing primary follow-up, and participants who were found to be HIV-1 infected are analyzed as non-dropouts, so the number of dropouts and number of early terminations need not match.	Enrollment until the date of dropout, through April 22, 2013 (up to Month 24 visit)
Primary	Participant Dropout After Unblinding	The trial was unblinded on April 23, 2013, and the protocol was in version 4 at the time.; For participants remaining uninfected, dropout is assessed only for primary follow-up, i.e. clinic visits. Protocol versions 4 and earlier included 24 months of primary follow-up, and versions 5 and later included 48 months. Participants may terminate early after completing primary follow-up, and participants who were found to be HIV-1 infected are analyzed as non-dropouts, so the number of dropouts and number of early terminations need not match.	April 23, 2013 through trial closure (up to Month 48 visit)
Primary	HIV-1 Infections Diagnosed After Day 0 Including All Available Follow-up Through the Maximum Month 48 Visit	For time-to-event analysis, an event is defined as HIV-1 infection and participants are censored if they dropped out early or completed the trial. HIV-1 diagnosis date is defined as the date of the earliest specimen collection yielding a positive HIV test. Participants remaining uninfected were censored at the latest specimen collection with a negative HIV-1 test.	Enrollment through Month 48 visit
Primary	HIV-1 Infections Diagnosed After Day 0 Through the Month 24 Visit	For time-to-event analysis, an event is defined as HIV-1 infection and participants remaining uninfected through the month 24 visit were censored. HIV-1 diagnosis date is defined as the date of the earliest specimen collection at or prior to month 24 which yielded a positive HIV test. Participants remaining uninfected through the month 24 visit were censored at the latest specimen collection with a negative HIV-1 test at or prior to the month 24 visit.	Enrollment through Month 24 visit
Primary	Number of Participants Experiencing Local Reactogenicity: Pain and/or Tenderness	For each sign or symptom, we define the maximum observed grade for each participant over all vaccinations and post-vaccination assessments. Local and systemic signs and symptoms are assessed and graded based on The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December, 2004 (Clarification dated August 2009). Local reactogenicity parameters are pain, tenderness, erythema, and induration. We present the maximum grade for pain and/or tenderness, and erythema and/or induration.	Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination
Primary	Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration	For each sign or symptom, we define the maximum observed grade for each participant over all vaccinations and post-vaccination assessments. Local and systemic signs and symptoms are assessed and graded based on The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December, 2004 (Clarification dated August 2009). Local reactogenicity parameters are pain, tenderness, erythema, and induration. We present the maximum grade for pain and/or tenderness, and erythema and/or induration.	Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination
Primary	Number of Participants Experiencing Systemic Reactogenicity	For each sign or symptom, we define the maximum observed grade for each participant over all vaccinations and post-vaccination assessments. Local and systemic signs and symptoms are assessed and graded based on The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December, 2004 (Clarification dated August 2009). Systemic reactogenicity parameters are malaise/fatigue, myalgia, headache, nausea, vomiting, chills, and arthralgia. We present the maximum grade calculated over these parameters.	Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination