Safety and Immunogenicity Study of Ad26-ENVA and Ad35-ENV HIV Vaccines in Healthy HIV-uninfected Adults

This study has been completed.
Sponsor:
Collaborators:
HIV Vaccine Trials Network
Beth Israel Deaconess Medical Center
Ragon Institute of MGH, MIT and Harvard
Information provided by (Responsible Party):
International AIDS Vaccine Initiative
ClinicalTrials.gov Identifier:
NCT01215149
First received: October 4, 2010
Last updated: December 13, 2012
Last verified: December 2012
  Purpose

The purpose of this study is to evaluate the safety and tolerability of Ad26.ENVA.01 and Ad35-ENV in low-risk for HIV-uninfected healthy adults administered in heterologous and homologous prime-boost regimens at different time intervals.


Condition Intervention Phase
HIV Infections
Biological: Ad35-ENV vaccine
Biological: Ad26.ENVA.01 vaccine
Biological: Placebo Control
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1 Placebo-controlled, Double-blind, Randomized Trial to Evaluate the Safety and Immunogenicity of Ad26-ENVA and Ad35-ENV HIV Vaccines in Healthy HIV-uninfected Adult Volunteers

Resource links provided by NLM:


Further study details as provided by International AIDS Vaccine Initiative:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 15-18 months approximately ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of Ad26.ENVA.01 and Ad35-ENV administered in heterologous and homologous prime-boost regimens.


Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    • To evaluate the immunogenicity of Ad26.ENVA.01 and Ad35-ENV administered in heterologous prime-boost regimens at 3 versus 6 month intervals
    • To evaluate the immunogenicity of Ad26.ENVA.01 and Ad35-ENV administered in heterologous and homologous prime-boost regimens at 3 month interval
    • To evaluate anti-vector immunity induced by Ad26.ENVA.01 and Ad35-ENV administered in heterologous and homologous prime-boost regimens


Enrollment: 218
Study Start Date: October 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Ad26.ENVA.01 at Month 0 followed by Ad35-ENV at Month 6. Vaccine:Placebo=10:3
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group B
Ad35-ENVA at Month 0 followed by Ad26.ENVA.01 at Month 6. Vaccine:Placebo=10:3
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group C
Ad26.ENVA.01 at Month 0 followed by Ad35-ENV at Month 3. Vaccine:Placebo=10:3
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group D
Ad35-ENV at Month 0 followed by Ad26.ENVA.01 at Month 3. Vaccine:Placebo=10:3
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group E
Ad26.ENVA.01 at Month 0 followed by Ad35-ENV at Month 3. Vaccine:Placebo=16:4
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group F
Ad35-ENV at Month 0 followed by Ad26.ENVA.01 at Month 3. Vaccine:Placebo=16:4
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group G
Ad26.ENVA.01 at Month 0 followed by Ad26.ENVA.01 at Month 3. Vaccine:Placebo=16:4
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group H
Ad35-ENV at Month 0 followed by Ad35-ENV at Month 3. Vaccine:Placebo=16:4
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group I
Ad26.ENVA.01 at Month 0 followed by Ad35-ENV at Month 3. Vaccine:Placebo=16:4
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group J
Ad35-ENV at Month 0 followed by Ad26.ENVA.01 at Month 3. Vaccine:Placebo=16:4
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group K
Ad26.ENVA.01 at Month 0 followed by Ad26.ENVA.01 at Month 3. Vaccine:Placebo=16:4
Biological: Ad26.ENVA.01 vaccine
Recombinant adenovirus serotype 26 vector vaccine, 5x10^10 vp delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer
Experimental: Group L
Ad35-ENV at Month 0 followed by Ad35-ENV at Month 3. Vaccine:Placebo=16:4
Biological: Ad35-ENV vaccine
Recombinant adenovirus serotype 35 vector vaccine 5x10^10 vp, delivered IM
Biological: Placebo Control
Colorless 10mm Tris/HCl buffer

Detailed Description:

The study is a randomized, double-blind placebo-controlled trial assessing the order of vector priming and boosting (Ad26 versus Ad35), the timing of boost (3 versus 6 months) and the homologous versus heterologous regimen at the 3-month time interval. Groups A-D will be enrolled in Boston, MA, USA, Groups E-H will be enrolled at the East African Clinical Research Centres and Groups I-L will be enrolled at the South African Clinical Research Centres.

Volunteers will be screened up to 56 days before vaccination and will be followed for 12 months after the second vaccination.

Approximately 212 volunteers will be randomized to receive either vaccine or placebo within a group (A-L); Groups A-D, Groups E-H and Groups I-L will be randomized separately. Up to 7% over-enrolment (approximately 15 volunteers) will be allowed to facilitate enrolment.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male or female, as assessed by a medical history, physical exam, and laboratory tests;
  • At least 18 years of age on the day of screening and has not reached his/her 51st birthday on the day of first vaccination;
  • Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study;
  • In the opinion of the Principal Investigator or designee, and based on Assessment of Informed Consent Understanding (AOU) results, has understood the information provided and potential risks linked to vaccination and participation in the trial; written informed consent will be provided by the volunteer before any study-related procedures are performed;
  • Willing to undergo HIV testing, risk reduction counselling, receive HIV test results and committed to maintaining low risk behaviour for the trial duration as defined by the protocol;
  • If a female of childbearing potential, willing to use an effective non-barrier method of contraception (oral or injectable hormonal contraceptive; intrauterine device [IUD]) from screening until at least 4 months after the last study vaccination;
  • Assessed by the clinic staff as being at "low risk" for HIV infection on the basis of sexual behaviours within the 12 months prior to enrolment;
  • All female volunteers must be willing to undergo pregnancy tests at time points indicated in the protocol and must test negative prior to each study vaccination;
  • All sexually active males (unless anatomically sterile) must be willing to use an effective method of contraception (such as consistent condom use) from the day of first vaccination until at least 4 months after the last vaccination;
  • Willing to forgo donations of blood or any other tissues during the study and, for those who test HIV positive due to trial vaccination (vaccine-induced HIV seropositivity), until the anti-HIV antibody titers become undetectable.

Exclusion Criteria

  • Confirmed HIV-1 or HIV-2 infection;
  • Any clinically relevant abnormality on history or examination including history of immunodeficiency or autoimmune disease; use of systemic corticosteroids (the use of topical or inhaled steroids is permitted); immunosuppressive, anticancer, antituberculosis or other medications considered significant by the investigator within the previous 6 months;
  • Any clinically significant acute or chronic medical condition that is considered progressive, or in the opinion of the investigator, makes the volunteer unsuitable for participation in the study;
  • Reported risky behaviour for HIV infection within 12 months prior to vaccination, as defined by the protocol
  • If female, pregnant or planning a pregnancy within 4 months after last vaccination; or lactating;
  • Asthma requiring high-dose oral or inhaled corticosteroids;
  • Fever > 100.4° F/38.0° C within 72 hours prior to vaccine administration;
  • Bleeding disorder that was diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions) (Note: A volunteer who states that he or she has easy bruising or bleeding, but does not have a formal diagnosis and has IM injections and blood draws without any adverse experience is eligible);
  • History of splenectomy;
  • Any abnormal laboratory parameters as defined by the protocol;
  • Receipt of live-attenuated vaccine within the previous 60 days or planned receipt within 60 days after vaccination with Investigational Product (within 14 days for live attenuated influenza vaccine [LAIV]); or receipt of other vaccine (e.g., influenza, pneumococcal), allergy treatment with antigen injections or tuberculin skin test within the previous 14 days or planned receipt within 14 days after vaccination with Investigational Product;
  • Receipt of blood transfusion or blood-derived products within the previous 3 months;
  • Participation in another clinical trial of an Investigational Product currently, within the previous 3 months or expected participation during this study;
  • Receipt of another investigational HIV vaccine candidate (Note: receipt of an HIV vaccine control or placebo will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval);
  • History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulty, angioedema);
  • Confirmed diagnosis of active hepatitis B, hepatitis C or active syphilis;
  • Seizure disorder: A participant who has had a seizure in the last 3 years is excluded. (Not excluded: a participant with a history of seizures who has neither required medications nor had a seizure for 3 years.);
  • Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01215149

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Kenya
Kenya AIDS Vaccine Initiative
Kangemi, Kenya
Rwanda
Projet San Francisco
Kigali, Rwanda
South Africa
Desmond Tutu HIV Foundation-Emavundleni Research Centre
Cape Town (Nyanga), South Africa
Aurum Institute
Klerksdorp, South Africa
Perinatal HIV Research Unit
Soweto, South Africa
Sponsors and Collaborators
International AIDS Vaccine Initiative
HIV Vaccine Trials Network
Beth Israel Deaconess Medical Center
Ragon Institute of MGH, MIT and Harvard
Investigators
Principal Investigator: Lindsey Baden, MD Brigham and Women's Hospital, Boston, MA, USA
Principal Investigator: Gaudensia Mutua, MB ChB, MPH Kenya AIDS Vaccine Initiative, Kangemi, Kenya
Principal Investigator: Etienne Karita, MD, M.Sc., MSPH Projet San Francisco
Principal Investigator: Linda-Gail Bekker, MD Desmond Tutu HIV Foundation-Emavundleni Research Center
Principal Investigator: Glenda Gray, MBBCH, FCPaeds(SA) Perinatal HIV Research Unit
Principal Investigator: Liesl Page-Shipp Aurum Institute
  More Information

Additional Information:
No publications provided

Responsible Party: International AIDS Vaccine Initiative
ClinicalTrials.gov Identifier: NCT01215149     History of Changes
Other Study ID Numbers: IAVI B003/ IPCAVD-004
Study First Received: October 4, 2010
Last Updated: December 13, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by International AIDS Vaccine Initiative:
HIV

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on August 28, 2014