Safety and Immunogenicity Study of 2 Investigational Preventive HIV Vaccines

HIV Infections Clinical Trial

Official title:

A Phase I Double-blinded, Placebo-controlled, Randomized Trial in HIV-uninfected, Healthy Adult Volunteers to Evaluate the Safety and Immunogenicity of an Adjuvanted GSK HIV Vaccine Administered With Ad35-GRIN Investigational Vaccine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01264445
• Other study ID #: IAVI B002
• Status: Completed
• Phase: Phase 1
• First received: December 20, 2010
• Last updated: February 8, 2013
• Start date: February 2011
• Est. completion date: November 2012

Study information

• Verified date: February 2013
• Source: International AIDS Vaccine Initiative
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUganda: Uganda Virus Research Institute, Science and Ethics Committee (UVRI SEC)Uganda: National Drug AuthorityUganda: Pharmacy and Poisons BoardKenya: Kenyatta National Hospital/University of Nairobi Ethics and Research CommitteeKenya: National Council for Science and Technology (NCST)Zambia: University of Zambia Biomedical Research Ethics Committee (UNZAREC)Zambia: Emory Institutional Review BoardZambia: Pharmacy Regulatory AuthorityZambia: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of an adjuvanted GSK investigational HIV vaccine and Ad35-GRIN in 4 different regimens at months 1, 2, 3, and 4.

Description:

Volunteers will be screened up to 42 days before vaccination (up to 90 days for Ad35 neutralizing antibody) and will be followed for 12 months after the last vaccination (16 months total participation).

It is estimated that it will take approximately 5 months to complete enrolment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Healthy males and females, as assessed by a medical history, physical exam, and laboratory tests

2. At least 18 years of age on the day of screening and has not reached his/her 41st birthday on the day of first vaccination

3. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study (screening plus 16 months)

4. In the opinion of the Principal Investigator or designee and based on Assessment of Informed Consent Understanding results, has understood the information provided and potential risks linked to vaccination and participation in the trial. Written informed consent needs to be provided by the volunteer before any study-related procedures are performed

5. Willing to undergo HIV testing, risk reduction counselling, receive HIV test results and committed to maintaining low risk behaviour for the trial duration

6. If a female of childbearing potential (not menopausal or anatomically sterile), willing to use an effective non-barrier method of contraception (hormonal contraceptive; intra-uterine device), from screening until four months after last vaccination. All female volunteers must be willing to undergo urine pregnancy tests at time points as indicated in the study protocol and must test negative prior to each vaccination.

7. If sexually active male (who is not anatomically sterile), willing to use an effective method of contraception (such as consistent condom use) from the day of first vaccination until 4 months after the last vaccination

8. Willing to forgo donations of blood or any other tissues during the study and, for those who test HIV positive after vaccination, until the anti-HIV antibody titres become undetectable

Exclusion Criteria:

1. Confirmed HIV-1 or HIV-2 infection

2. Any clinically relevant abnormality on history or examination including history of immunodeficiency, malignancy or autoimmune disease; use of systemic corticosteroids (<2 weeks use of topical or inhaled steroids is permitted); immunosuppressive, anticancer, anti-tuberculosis or other medications considered significant by the investigator within the previous 6 months

3. 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

4. Detection of Ad35-specific serum neutralizing antibody

5. Reported high-risk behaviour for HIV infection within 6 months prior to first vaccination, as defined by the protocol.

6. If female, pregnant or planning a pregnancy within 4 months after last vaccination; or lactating

7. Unstable asthma (e.g. sudden acute attacks occurring without an obvious trigger) or asthma requiring:

• Daily steroid or long acting beta-agonist prevention

• Hospitalization in the last two years

8. Bleeding disorder that was diagnosed by a physician e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions. (A volunteer who states that he or she has easy bruising or bleeding, but does not have a formal diagnosis and has intramuscular (IM) injections and blood draws without any adverse experience is eligible)

9. History of splenectomy

10. Any abnormal laboratory parameters as defined by the protocol;

11. Receipt of live-attenuated vaccine within the previous 60 days (live attenuated flu vaccine within 14 days) or planned receipt within 60 days after vaccination with Investigational Product; or receipt of other vaccine (e.g. 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

12. Receipt of blood transfusion or blood-derived products within the previous 6 months

13. Participation in another clinical trial of an Investigational Product currently, within the previous 3 months or expected participation during this study

14. Prior receipt of another investigational HIV vaccine candidate (note: receipt of an HIV vaccine placebo will not exclude a volunteer from participation if documentation is available and the IAVI Medical Monitor gives approval)

15. History of severe local or systemic reactogenicity to vaccines (e.g. anaphylaxis, respiratory difficulty, angioedema)

16. History of severe allergic reactions to any substance requiring hospitalization or emergency medical care (e.g. Steven-Johnson syndrome, bronchospasm or hypotension)

17. Known sensitivity to sulphite, aspirin or aminoglycoside antibiotics (e.g. amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, tobramycin, etc)

18. Confirmed diagnosis of active hepatitis B (HBsAg), hepatitis C (HCV antibodies), active syphilis or active tuberculosis

19. History of severe neurological disorder, seizure or psychiatric disorder (e.g schizophrenia, severe psychosis, bipolar disorder requiring therapy, suicidal attempt or ideation)

20. For those volunteers at clinical centres participating in ophthalmic examinations, any clinically significant abnormality found on baseline ophthalmic examination.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• Adjuvanted GSK investigational HIV vaccine formulation 1
Receive at Months 0 and 1
• Adjuvanted GSK investigational HIV vaccine formulation 2
Receive at Months 0 and 1
• Ad35 investigational HIV vaccine
Receive at Month 0
• Adjuvanted GSK investigational HIV vaccine formulation 2
Receive at Months 3 and 4
• Adjuvanted GSK investigational HIV vaccine formulation 2
Receive at Months 0, 1, and 4
• Ad35 investigational HIV vaccine
Receive at Month 4
• Ad35 investigational HIV vaccine
Receive at Months 0, 1, and 4
• Placebo (saline)
(Vaccine:Placebo=28:7) Groups A, B, C, and D will all have a placebo comparator component (7 volunteers will receive placebo in each group at the specified months.)

Locations

Country	Name	City	State
Kenya	Kenya AIDS Vaccine Initiative	Nairobi
Uganda	Uganda Virus Research Institute-IAVI	Entebbe
Uganda	Medical Research Council	Masaka
Zambia	Zambia-Emory HIV Research Project	Lusaka

Sponsors (2)

Lead Sponsor	Collaborator
International AIDS Vaccine Initiative	GlaxoSmithKline

Countries where clinical trial is conducted

Kenya,  Uganda,  Zambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of an adjuvanted HIV protein vaccine in prime-boost combinations with AD35-GRIN or coadministered with AD35-GRIN	Safety of an adjuvanted (dose escalation for adjvans) HIV protein vaccine given as prime or boost in combination with Ad35-GRIN or co-administered with Ad35-GRIN	16 months	Yes
Secondary	Immunogenicity of an adjuvanted HIV protein vaccine given in different prime-boost regimens with Ad35-GRIN or coadminisitered with Ad35-GRIN		16 months	No

External Links

•   International AIDS Vaccine Initiative