Clinical trial NCT00434512: Dose-ranging Study to Evaluate the Safety & Immunogenicity of a HIV Vaccine 732461 in Healthy HIV Seronegative Volunteers
Official title: A Dose-ranging Study to Compare the Safety and Immunogenicity of a Candidate Human Deficiency Virus (HIV) Vaccine 732461, Adjuvanted or Not, Administered According to a 0, 1 Month Schedule to Healthy Adult HIV Seronegative Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: AIDS
HIV Infections
Keywords: Gag
vaccine
adjuvant
HIV
Pol
Nef
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-02-13
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: GSK has constructed a new HIV immunogen comprised of conserved parts of the HIV virus (gag, pol and nef). The principal objectives of this study are to evaluate the reactogenicity and safety of this candidate vaccine with or without a GSK proprietary adjuvant system at three different doses and to evaluate the CD4+ T-cell response in terms of proportion of responders to the antigens two weeks after the second vaccination.

Detailed description: This is a single center, observer-blind, randomized, dose-escalating, staggered study with 6 groups: 3 groups of 50 subjects receiving the adjuvanted candidate vaccine, at 3 different doses and 3 groups of 10 subjects receiving the non-adjuvanted candidate vaccine in water for injection, at 3 different doses. The vaccination schedule will be 0-1 month. Blood samples will be collected at 8 visits. The duration of the study will be approximately 14 months for each subject. Rationale for Protocol Posting Amendment: The third vaccination will be cancelled and the visit at Month 7 will be postponed to Month 9. The Protocol Posting has also been updated in order to comply with the FDA Amendment Act, Sep 2007.

Eligibility criteria: Inclusion Criteria:

* A male or female between and including 18-40 years at the time of first vaccination.
* Written informed consent obtained from the subject prior to any study procedure.
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
* Good general health without significant medical history, physical examination findings, or clinically significant abnormal laboratory results.
* If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.
* Negative for antibodies against HIV-1, HIV-2 and negative for HIV p24 antigen within 56 days (8 weeks) prior to enrolment. Subjects must be willing to accept HIV test results. Individuals who elect not to receive test results will not be enrolled.
* Negative for anti-HBc Ab, HBsAg and anti-HCV Ab.

Exclusion Criteria:

* Women who are pregnant or breast-feeding.
* Subjects with a history of, or current, alcohol or substance abuse.
* The subject is at high risk of acquiring HIV according to the behavioural risk assessment questionnaire.
* Morbid obesity
* Previous inclusion in a HIV vaccines trial.
* Receipt of live attenuated vaccines within 30 days of enrolment.
* Receipt of medically indicated subunit or killed vaccines or allergy treatment with antigen injections within 14 days of study vaccine administration.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Prior receipt of HIV-1 vaccines or placebo in a previous HIV vaccine trial.
* Receipt of blood products 120 days prior to HIV screening.
* Receipt of immunoglobulin 120 days prior to HIV screening.
* History of serious adverse reactions including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema and abdominal pain to vaccines.
* History of serious allergic reaction to any substance requiring hospitalization or emergency medical care.
* History of immunodeficiency or autoimmune disease.
* History of malignancy (unless there has been surgical excision followed by a sufficient observation period, of at least 5 years, to give a reasonable assurance of sustained cure and which, in the estimate of the investigator, is not likely to recur during the study period).
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccination.
* History of type I or type II diabetes mellitus including cases controlled with diet alone. A subject with past gestational diabetes is eligible.
* Thyroid disease including history of thyroidectomy and diagnoses requiring medication. A subject not requiring thyroid medicine within the past 12 months is eligible.
* Acute disease at the time of enrolment.
* Asthma requiring daily steroid or long acting β agonist prevention.
* Unstable asthma.
* Food- or wine-induced asthma.
* Known sensitivity to sulfites or aspirin.
* Bleeding disorder that was diagnosed by a physician. A subject who states that he or she has easy bruising or bleeding, but does not carry a formal diagnosis and has intramuscular (IM) injections and blood draws without any adverse experience is eligible.
* History of any serious neurologic disorder or seizure
* History of major congenital defect
* History of chronic fatigue syndrome or fibromyalgia
* Splenectomy
* Hypertension. A subject with hypertension is eligible if he or she is controlled on medication and the documented blood pressure is less than 150/100.
* Any medical, psychiatric or social condition, or occupational or other responsibility that, in the judgement of the investigator, would interfere with or serve as a contradiction to adherence to the study protocol or ability to give informed consent.

Primary outcomes:
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) follow-up period after each vaccination and overall (across doses)
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) follow-up period after each vaccination and overall (across doses)
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) follow-up period after vaccination (across doses)
measure: Number of Subjects With Serious Adverse Events (SAEs) and Related SAEs
timeFrame: During the whole study period (From Month 0 up to Month 12)
measure: Number of Subjects With Abnormal Haematological and Biochemical Levels at Month 0
timeFrame: At Month 0
measure: Number of Subjects With Abnormal Haematological and Biochemical Levels at Month 1
timeFrame: At Month 1
measure: Number of Subjects With Abnormal Haematological and Biochemical Levels at Day 44
timeFrame: At Day 44
measure: Number of Subjects With Abnormal Haematological and Biochemical Levels at Month 2
timeFrame: At Month 2
measure: Number of Subjects With Abnormal Haematological and Biochemical Levels at Month 6
timeFrame: At Month 6
measure: Number of Subjects With Abnormal Haematological and Biochemical Levels at Month 9
timeFrame: At Month 9
measure: Number of Subjects With Abnormal Haematological and Biochemical Levels at Month 12
timeFrame: At Month 12
measure: Number of Subjects With a Response in Terms of Cluster of Differentiation 4 (CD4+) T-cells Expressing at Least Two Cytokines Including IL-2 Equal or Above the Cut-off to at Least 1, 2, 3 Antigens and to All 4 Antigens
timeFrame: At Day 44
Secondary outcomes:
measure: Frequency of p17, p24, Nef and RT-specific CD4+ T-cells Expressing IL-2 and at Least Another Marker
timeFrame: At Month 0, Day 44, Month 2, Month 6 and Month 12
measure: Frequency of p17, p24, Nef and RT-specific CD4+ T-cells Expressing at Least 2 Immune Markers
timeFrame: At Month 0, Day 44, Month 2, Month 6 and Month 12
measure: Antibody Titers Against p17, p24, Nef, RT and F4co Antigens
timeFrame: At Month 0, Day 44, Month 2, Month 6 and Month 12
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Leroux-Roels G, Bourguignon P, Willekens J, Janssens M, Clement F, Didierlaurent AM, Fissette L, Roman F, Boutriau D. Immunogenicity and safety of a booster dose of an investigational adjuvanted polyprotein HIV-1 vaccine in healthy adults and effect of administration of chloroquine. Clin Vaccine Immunol. 2014 Mar;21(3):302-11. doi: 10.1128/CVI.00617-13. Epub 2014 Jan 3.
citation: Van Braeckel E, Koutsoukos M, Bourguignon P, Clement F, McNally L, Leroux-Roels G. Vaccine-induced HIV seropositivity: a problem on the rise. J Clin Virol. 2011 Apr;50(4):334-7. doi: 10.1016/j.jcv.2011.01.003.
citation: Van Braeckel E, Bourguignon P, Koutsoukos M, Clement F, Janssens M, Carletti I, Collard A, Demoitie MA, Voss G, Leroux-Roels G, McNally L. An adjuvanted polyprotein HIV-1 vaccine induces polyfunctional cross-reactive CD4+ T cell responses in seronegative volunteers. Clin Infect Dis. 2011 Feb 15;52(4):522-31. doi: 10.1093/cid/ciq160. Epub 2011 Jan 5.