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Safety of and Immune Response to an Adenoviral HIV-1 Vaccine in Healthy Adults

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ad26.ENVA.01 HIV-1 vaccine

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring HIV Seronegativity, HIV Preventative Vaccine

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Good general health with normal hematological, hepatic and renal functions
Demonstrated understanding of study
Willing to receive HIV test results
HIV-1 and -2 uninfected
Hepatitis B surface antigen negative
Anti-hepatitis C virus (anti-HCV) negative antibody or negative HCV PCR if anti-HCV is positive
Appropriate hemoglobin, white blood cell, lymphocyte, and platelet count values as defined in the study protocol
Certain laboratory values as defined in the study protocol
Adequate contraception from at least 21 days prior to study entry through visit 10

Exclusion Criteria:

HIV vaccines or placebos in prior HIV vaccine trial
Immunosuppressive medications within 168 days prior to first injection. Participants taking corticosteroid nasal spray or topical corticosteroids are not excluded.
Blood products within 120 days prior to first injection
Immunoglobulin within 60 days prior to first injection
Investigational agents within 30 days prior to first injections
Live attenuated vaccine within 30 days prior to first injection
Any vaccine not a live attenuated vaccine within 14 days prior to first injection
Any clinically significant medical condition that, in the opinion of the investigator, may interfere with the study
Any medical, psychiatric, occupational, or social condition or responsibility that, in the opinion of the investigator, would interfere with the study
Serious adverse reaction to vaccines. Participants who had a nonanaphylactic adverse reaction to pertussis vaccine as a child are not excluded.
Known autoimmune disease
Known immunodeficiency
Asthma other than mild and/or well-controlled asthma
Active syphilis infection. Those fully treated for syphilis over 6 months prior to study entry are not excluded.
Diabetes mellitus type 1 or 2
Thyroidectomy or thyroid disease requiring medication within 12 months prior to study entry
Angioedema in the 3 years prior to study entry if the episodes are considered serious or have required medication within the last 2 years
Hypertension. More information on this criterion can be found in the protocol.
Body mass index (BMI) of 40 or higher OR BMI of 35 or greater, if other cardiovascular risk factors. More information on this criterion can be found in the protocol.
Bleeding disorder
Malignancy, unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period
Seizure disorder or occurrence of seizure in the 3 years prior to study entry. Participants who have not required medications or had a seizure for prior 3 years are not excluded.
Absence of a functional spleen
Psychiatric condition within the last 3 years. More information on this criterion can be found in the study protocol.
Individuals at high-risk of acquiring HIV infection
Presence of pre-existing neutralizing antibodies for Adenovirus 26
Pregnancy or breastfeeding

Sites / Locations

Brigham and Women's Hosp. Novel Adenoviral Vector Prophylactic HIV Vaccine Non-Network CRS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Arm Description

3 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at 1 x 10^9 virus particles (VP) given at Days 0, 28, and 168

3 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at 1 x 10^10 VP given at Days 0, 28, and 168

3 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at 1 x 10^11 VP given at Days 0, 28, and 168

2 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at a dose to be determined by the safety data from Arms 1, 2 and 3 given at Days 0 and 168

Outcomes

Primary Outcome Measures

Local and systemic reactions to injection

Secondary Outcome Measures

Humoral immune responses, such as neutralizing and binding antibodies to HIV and Ad26

Cell mediated immunity, including T-cell gamma interferon responses and assessment of T-cell responses by flow cytometry

Genotyping

Stored samples may be used to perform additional assays for further evaluation of immunogenicity and to support standardization and validation of new assays such as epitope mapping, flow cytometry, and/or tetramer analysis.

Full Information

NCT ID

NCT00618605

First Posted

February 18, 2008

Last Updated

October 28, 2021

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT00618605

Brief Title

Safety of and Immune Response to an Adenoviral HIV-1 Vaccine in Healthy Adults

Official Title

A Phase 1 Randomized, Double-Blind, Placebo Controlled Dose Escalation Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant Adenovirus Serotype 26 HIV-1 Vaccine (Ad26.ENVA.01) in Healthy, HIV-1 Uninfected Adults

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

February 2008 (undefined)

Primary Completion Date

July 2011 (Actual)

Study Completion Date

October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Successful control of the HIV epidemic will require a safe and effective vaccine to be developed. A successful vaccine will need to stimulate a widespread immune response. The purpose of this study is to determine the safety of and immune response to an adenovirus serotype HIV vaccine in HIV uninfected adults.

Detailed Description

HIV infection continues to spread at pandemic levels throughout the world. Control of this pandemic can only be achieved with the development of a safe and effective preventive HIV vaccine. A vaccine that will prevent HIV infection will elicit a strong immune response from both CD4 and CD8 cells. Recombinant adenovirus serotype vectors have been shown to elicit just such a response. The purpose of this study is to determine the safety and immunogenicity of the recombinant adenovirus serotype 26 preventive HIV-1 vaccine. This study will last 12 months. Participants will be randomly assigned to one of four arms that will receive different doses of the vaccine or placebo administered via intermuscular injection. Participants in Arms 1, 2, and 3 will all receive 3 injections. Each injection will contain the same dose of vaccine. Arm 4 will receive 2 injections of a dose of vaccine that will be determined by the safety data from Arms 1, 2, and 3. Participants will be enrolled sequentially, from lowest to highest dose of vaccine, into Arms 1, 2, and 3. Arms will begin enrollment only following review of safety data from the previous group. After the Day 42 safety data from Arms 1, 2, and 3 have been reviewed, the dose for Arm 4 will be determined, and enrollment into that arm will begin. There will be 10 study visits in this study, occurring at baseline and after 0.5, 1, 1.5, 2, 6, 6.5, 7, and 12 months. Participants in Arms 1, 2, and 3 will receive injections on Days 0, 28, and 168. Participants in Arm 4 will receive injections on Days 0 and 168. Participants will be asked to record their temperature and other side effects in a symptom log for 7 days after each injection. Risk reduction/pregnancy prevention counseling will occur at visits 1 through 9, and physical exams and assessments of illness or adverse events will occur at all visits. At most visits, blood, urine, and oral swab collection will occur. At some visits, HIV testing and pregnancy testing will occur. Once a year for 5 years following study entry, participants will attend a study visit or will be contacted by study staff by telephone or e-mail for follow-up safety and health monitoring. Some participants will also undergo a blood collection at these visits.

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 Preventative Vaccine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

3 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at 1 x 10^9 virus particles (VP) given at Days 0, 28, and 168

Arm Title

Arm Type

Experimental

Arm Description

3 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at 1 x 10^10 VP given at Days 0, 28, and 168

Arm Title

Arm Type

Experimental

Arm Description

3 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at 1 x 10^11 VP given at Days 0, 28, and 168

Arm Title

Arm Type

Experimental

Arm Description

2 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at a dose to be determined by the safety data from Arms 1, 2 and 3 given at Days 0 and 168

Intervention Type

Biological

Intervention Name(s)

Ad26.ENVA.01 HIV-1 vaccine

Intervention Description

Recombinant adenovirus serotype 26 HIV-1 vaccine

Primary Outcome Measure Information:

Title

Local and systemic reactions to injection

Time Frame

After each injection

Secondary Outcome Measure Information:

Title

Humoral immune responses, such as neutralizing and binding antibodies to HIV and Ad26

Time Frame

Throughout study

Title

Cell mediated immunity, including T-cell gamma interferon responses and assessment of T-cell responses by flow cytometry

Time Frame

Throughout study

Title

Genotyping

Time Frame

Throughout study

Title

Time Frame

After study follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Good general health with normal hematological, hepatic and renal functions Demonstrated understanding of study Willing to receive HIV test results HIV-1 and -2 uninfected Hepatitis B surface antigen negative Anti-hepatitis C virus (anti-HCV) negative antibody or negative HCV PCR if anti-HCV is positive Appropriate hemoglobin, white blood cell, lymphocyte, and platelet count values as defined in the study protocol Certain laboratory values as defined in the study protocol Adequate contraception from at least 21 days prior to study entry through visit 10 Exclusion Criteria: HIV vaccines or placebos in prior HIV vaccine trial Immunosuppressive medications within 168 days prior to first injection. Participants taking corticosteroid nasal spray or topical corticosteroids are not excluded. Blood products within 120 days prior to first injection Immunoglobulin within 60 days prior to first injection Investigational agents within 30 days prior to first injections Live attenuated vaccine within 30 days prior to first injection Any vaccine not a live attenuated vaccine within 14 days prior to first injection Any clinically significant medical condition that, in the opinion of the investigator, may interfere with the study Any medical, psychiatric, occupational, or social condition or responsibility that, in the opinion of the investigator, would interfere with the study Serious adverse reaction to vaccines. Participants who had a nonanaphylactic adverse reaction to pertussis vaccine as a child are not excluded. Known autoimmune disease Known immunodeficiency Asthma other than mild and/or well-controlled asthma Active syphilis infection. Those fully treated for syphilis over 6 months prior to study entry are not excluded. Diabetes mellitus type 1 or 2 Thyroidectomy or thyroid disease requiring medication within 12 months prior to study entry Angioedema in the 3 years prior to study entry if the episodes are considered serious or have required medication within the last 2 years Hypertension. More information on this criterion can be found in the protocol. Body mass index (BMI) of 40 or higher OR BMI of 35 or greater, if other cardiovascular risk factors. More information on this criterion can be found in the protocol. Bleeding disorder Malignancy, unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period Seizure disorder or occurrence of seizure in the 3 years prior to study entry. Participants who have not required medications or had a seizure for prior 3 years are not excluded. Absence of a functional spleen Psychiatric condition within the last 3 years. More information on this criterion can be found in the study protocol. Individuals at high-risk of acquiring HIV infection Presence of pre-existing neutralizing antibodies for Adenovirus 26 Pregnancy or breastfeeding

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lindsey Baden, MD

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Dan Barouch, MD, PhD

Organizational Affiliation

Beth Israel Deaconess Medical Center

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Raphael Dolin, MD

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Brigham and Women's Hosp. Novel Adenoviral Vector Prophylactic HIV Vaccine Non-Network CRS

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115-6110

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17329340

Citation

Abbink P, Lemckert AA, Ewald BA, Lynch DM, Denholtz M, Smits S, Holterman L, Damen I, Vogels R, Thorner AR, O'Brien KL, Carville A, Mansfield KG, Goudsmit J, Havenga MJ, Barouch DH. Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D. J Virol. 2007 May;81(9):4654-63. doi: 10.1128/JVI.02696-06. Epub 2007 Feb 28.

Results Reference

background

PubMed Identifier

17408374

Citation

Liniger M, Zuniga A, Naim HY. Use of viral vectors for the development of vaccines. Expert Rev Vaccines. 2007 Apr;6(2):255-66. doi: 10.1586/14760584.6.2.255.

Results Reference

background

PubMed Identifier

16625206

Citation

Roberts DM, Nanda A, Havenga MJ, Abbink P, Lynch DM, Ewald BA, Liu J, Thorner AR, Swanson PE, Gorgone DA, Lifton MA, Lemckert AA, Holterman L, Chen B, Dilraj A, Carville A, Mansfield KG, Goudsmit J, Barouch DH. Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity. Nature. 2006 May 11;441(7090):239-43. doi: 10.1038/nature04721. Epub 2006 Apr 16.

Results Reference

background

PubMed Identifier

23125444

Citation

Baden LR, Walsh SR, Seaman MS, Tucker RP, Krause KH, Patel A, Johnson JA, Kleinjan J, Yanosick KE, Perry J, Zablowsky E, Abbink P, Peter L, Iampietro MJ, Cheung A, Pau MG, Weijtens M, Goudsmit J, Swann E, Wolff M, Loblein H, Dolin R, Barouch DH. First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001). J Infect Dis. 2013 Jan 15;207(2):240-7. doi: 10.1093/infdis/jis670. Epub 2012 Nov 2.

Results Reference

derived

PubMed Identifier

23125443

Citation

Barouch DH, Liu J, Peter L, Abbink P, Iampietro MJ, Cheung A, Alter G, Chung A, Dugast AS, Frahm N, McElrath MJ, Wenschuh H, Reimer U, Seaman MS, Pau MG, Weijtens M, Goudsmit J, Walsh SR, Dolin R, Baden LR. Characterization of humoral and cellular immune responses elicited by a recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD 001). J Infect Dis. 2013 Jan 15;207(2):248-56. doi: 10.1093/infdis/jis671. Epub 2012 Nov 2.

Results Reference

derived

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Safety of and Immune Response to an Adenoviral HIV-1 Vaccine in Healthy Adults

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