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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

Primary Purpose

HIV Infections

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

DNA plasmid vaccine

Recombinant adenoviral serotype 5 (rAD5) vector vaccine

DNA vaccine placebo

HIV-1 recombinant adenovirus vaccine placebo

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring HIV Seronegativity, HIV Preventive Vaccine, HIV Treatment Vaccine, Adenovirus

Eligibility Criteria

18 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

Alabama CRS
The AIDS Research Alliance of America CRS
UCLA CARE Center CRS
Bridge HIV CRS
University of Colorado Hospital CRS
Orlando Immunology Center CRS
The Hope Clinic of the Emory Vaccine Center CRS
UIC Project WISH CRS
VRC Clinical Trials Core CRS
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Fenway Health (FH) CRS
NY Univ. HIV/AIDS CRS
Columbia P&S CRS
New York Blood Center CRS
University of Rochester Vaccines to Prevent HIV Infection CRS
Case Clinical Research Site
Penn Prevention CRS
Vanderbilt Vaccine (VV) CRS
University of Texas Southwestern CRS
Baylor Vaccine Research Center CRS
Care-Id Crs
Seattle Vaccine and Prevention CRS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

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

Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped.

Outcomes

Primary Outcome Measures

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.

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.

Participant Dropout After Unblinding

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.

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.

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.

Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00865566

First Posted

March 17, 2009

Last Updated

October 13, 2021

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

HIV Vaccine Trials Network

1. Study Identification

Unique Protocol Identification Number

NCT00865566

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Terminated

Why Stopped

The trial was stopped for efficacy futility

Study Start Date

May 2009 (undefined)

Primary Completion Date

October 6, 2017 (Actual)

Study Completion Date

October 6, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

HIV Vaccine Trials Network

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

HIV Seronegativity, HIV Preventive Vaccine, HIV Treatment Vaccine, Adenovirus

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

2504 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Arm Title

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

DNA plasmid vaccine

Other Intervention Name(s)

VRC-HIVDNA016-00-VP

Intervention Description

4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid

Intervention Type

Biological

Intervention Name(s)

Recombinant adenoviral serotype 5 (rAD5) vector vaccine

Other Intervention Name(s)

VRC-HIVADV014-00-VP

Intervention Description

1 x 10^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid

Intervention Type

Biological

Intervention Name(s)

DNA vaccine placebo

Other Intervention Name(s)

VRC-PBSPLA043-00-VP, phosphate buffered saline (PBS)

Intervention Description

1 mL IM via Biojector® in either deltoid

Intervention Type

Biological

Intervention Name(s)

HIV-1 recombinant adenovirus vaccine placebo

Other Intervention Name(s)

VRC-DILUENT013-DIL-VP, final formulation buffer (FFB)

Intervention Description

1 mL administered IM by needle and syringe in either deltoid

Primary Outcome Measure Information:

Title

Participant Dropout Through Month 48

Description

Time Frame

Enrollment through Month 48 visit

Title

Participant Dropout Prior to Unblinding

Description

Time Frame

Enrollment until the date of dropout, through April 22, 2013 (up to Month 24 visit)

Title

Participant Dropout After Unblinding

Description

Time Frame

April 23, 2013 through trial closure (up to Month 48 visit)

Title

HIV-1 Infections Diagnosed After Day 0 Including All Available Follow-up Through the Maximum Month 48 Visit

Description

Time Frame

Enrollment through Month 48 visit

Title

HIV-1 Infections Diagnosed After Day 0 Through the Month 24 Visit

Description

Time Frame

Enrollment through Month 24 visit

Title

Number of Participants Experiencing Local Reactogenicity: Pain and/or Tenderness

Description

Time Frame

Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination

Title

Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration

Description

Time Frame

Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination

Title

Number of Participants Experiencing Systemic Reactogenicity

Description

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.

Time Frame

Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Scott Hammer

Organizational Affiliation

Columbia University

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Magdalena Sobieszczyk

Organizational Affiliation

Columbia University

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Michael Yin

Organizational Affiliation

Columbia University

Official's Role

Study Chair

Facility Information:

Facility Name

Alabama CRS

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

The AIDS Research Alliance of America CRS

City

Los Angeles

State/Province

California

ZIP/Postal Code

90015

Country

United States

Facility Name

UCLA CARE Center CRS

City

Los Angeles

State/Province

California

ZIP/Postal Code

90035

Country

United States

Facility Name

Bridge HIV CRS

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

University of Colorado Hospital CRS

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Orlando Immunology Center CRS

City

Orlando

State/Province

Florida

ZIP/Postal Code

32803

Country

United States

Facility Name

The Hope Clinic of the Emory Vaccine Center CRS

City

Decatur

State/Province

Georgia

ZIP/Postal Code

30030

Country

United States

Facility Name

UIC Project WISH CRS

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

VRC Clinical Trials Core CRS

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20816

Country

United States

Facility Name

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115-6110

Country

United States

Facility Name

Fenway Health (FH) CRS

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215-4302

Country

United States

Facility Name

NY Univ. HIV/AIDS CRS

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Columbia P&S CRS

City

New York

State/Province

New York

ZIP/Postal Code

10032-3732

Country

United States

Facility Name

New York Blood Center CRS

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

University of Rochester Vaccines to Prevent HIV Infection CRS

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

Case Clinical Research Site

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Name

Penn Prevention CRS

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Vanderbilt Vaccine (VV) CRS

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-2582

Country

United States

Facility Name

University of Texas Southwestern CRS

City

Dallas

State/Province

Texas

ZIP/Postal Code

75235

Country

United States

Facility Name

Baylor Vaccine Research Center CRS

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Care-Id Crs

City

Annandale

State/Province

Virginia

ZIP/Postal Code

22003

Country

United States

Facility Name

Seattle Vaccine and Prevention CRS

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109-1024

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

18443427

Citation

Lu S. Immunogenicity of DNA vaccines in humans: it takes two to tango. Hum Vaccin. 2008 Nov-Dec;4(6):449-52. doi: 10.4161/hv.4.6.6179. Epub 2008 Nov 28.

Results Reference

background

PubMed Identifier

19031031

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.

Results Reference

background

PubMed Identifier

20636279

Citation

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. doi: 10.2174/157016210793499286.

Results Reference

result

PubMed Identifier

24099601

Citation

Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, Koblin BA, Buchbinder SP, Keefer MC, Tomaras GD, Frahm N, Hural J, Anude C, Graham BS, Enama ME, Adams E, DeJesus E, Novak RM, Frank I, Bentley C, Ramirez S, Fu R, Koup RA, Mascola JR, Nabel GJ, Montefiori DC, Kublin J, McElrath MJ, Corey L, Gilbert PB; HVTN 505 Study Team. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med. 2013 Nov 28;369(22):2083-92. doi: 10.1056/NEJMoa1310566. Epub 2013 Oct 7.

Results Reference

derived

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