Safety and Immunogenicity Study of Three Candidate HIV-1 Vaccines, Administered in Combination to Healthy HIV-1 Uninfected Adults

NCT ID: NCT01151319

Last Updated: 2014-04-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2014-04-30

Brief Summary

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This is a randomised, placebo-controlled, single-blind study designed to evaluate the safety and immunogenicity of three novel HIV vaccines.

Detailed Description

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Conditions

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HIV-1 Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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Stage 1.

The first stage will start from a low and well tolerated, but likely less immunogenic dose of ChAdV63.HIVconsv (n=2).

Group Type EXPERIMENTAL

ChAdV63.HIVconsv low dose.

Intervention Type BIOLOGICAL

Attenuated chimp adenovirus. 5x10\^9 virus particles.

Stage 2

The highest dose of ChAdV63.HIVconsv followed by boost with MVA.HIVconsv at week 0 and 8, respectively (n=8). Followed up at 6,12 and 24 months after last vaccination.

Group Type EXPERIMENTAL

ChAdV63.HIVconsv high dose.

Intervention Type BIOLOGICAL

Attenuated chimp adenovirus at 5x10\^10 virus particles.

MVA.HIVconsv

Intervention Type BIOLOGICAL

Attenuated poxvirus at 4x10\^8 plaque forming units per dose.

Stage 3

Three doses of pSG2.HIVconsv DNA followed by boost with high dose ChAdV63.HIVconsv followed by boost with MVA.HIVconsv at week 0,4,8,12 and 20, respectively (n=8). Followed up at 6, 12 and 24 months after last vaccination.

Group Type EXPERIMENTAL

ChAdV63.HIVconsv high dose.

Intervention Type BIOLOGICAL

Attenuated chimp adenovirus at 5x10\^10 virus particles.

pSG2.HIVconsv

Intervention Type BIOLOGICAL

DNA at 4mg per dose.

MVA.HIVconsv

Intervention Type BIOLOGICAL

Attenuated poxvirus at 4x10\^8 plaque forming units per dose.

Stage 4

Three doses of pSG2.HIVconsv DNA followed by boost with MVA.HIVconsv followed by boost with high dose ChAdV63.HIVconsv at weeks at week 0,4,8,12 and 16, respectively (n=8).

Group Type EXPERIMENTAL

ChAdV63.HIVconsv high dose.

Intervention Type BIOLOGICAL

Attenuated chimp adenovirus at 5x10\^10 virus particles.

pSG2.HIVconsv

Intervention Type BIOLOGICAL

DNA at 4mg per dose.

MVA.HIVconsv

Intervention Type BIOLOGICAL

Attenuated poxvirus at 4x10\^8 plaque forming units per dose.

Stage 2 Placebo

Time-course matched to vaccinations (n=2)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Phosphate buffered saline

Stage 3 placebo

Time-course matched to vaccinations (n=2)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Phosphate buffered saline

Stage 4 placebo

Time-course matched to vaccinations (n=2)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Phosphate buffered saline

Interventions

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ChAdV63.HIVconsv low dose.

Attenuated chimp adenovirus. 5x10\^9 virus particles.

Intervention Type BIOLOGICAL

ChAdV63.HIVconsv high dose.

Attenuated chimp adenovirus at 5x10\^10 virus particles.

Intervention Type BIOLOGICAL

pSG2.HIVconsv

DNA at 4mg per dose.

Intervention Type BIOLOGICAL

MVA.HIVconsv

Attenuated poxvirus at 4x10\^8 plaque forming units per dose.

Intervention Type BIOLOGICAL

Placebo

Phosphate buffered saline

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Healthy males or females, as assessed by a medical history, physical examination and laboratory tests.
2. Aged at least 18 years on the day of screening and no greater than 50 years on the day of the first vaccination.
3. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
4. In the opinion of the principal investigator or designee, the volunteer has understood the information provided. Written informed consent must be given before any study-related procedures are performed.
5. Willing to undergo HIV-1 testing, HIV-1 counselling and receive HIV-1 test results.
6. If heterosexually active female; using an effective method of contraception (e.g. hormonal contraception, diaphragm, intra-uterine device (IUD), condoms, anatomical sterility in self or partner) from 14 days prior to the first vaccination until at least 6 weeks after the last vaccination; all female volunteers must be willing to undergo urine pregnancy tests at time points specified in the protocol.
7. If heterosexually active male; willing to use an effective method of contraception (condoms; anatomical sterility in self or partner) from the day of the first vaccination until 6 weeks after the last vaccination.
8. Willing to forgo donations of blood during the study.

Exclusion Criteria

1. Any clinically significant acute or chronic medical condition that is considered progressive or, in the opinion of the principal investigator or designee, would make the volunteer unsuitable for the study.
2. Any of the following abnormal laboratory parameters listed below:

Haematology
* Haemoglobin \< 10.0 g/dl
* Absolute Neutrophil Count (ANC) ≤ 1000 /mm3 (≤ 1 x 109 /l)
* Absolute Lymphocyte Count (ALC) ≤ 600 /mm3 (≤ 1 x 109 /l)
* Platelets ≤100,000 /mm3, ≥ 550,000 /mm3 (≤ 90 /l, ≥ 550 /l) Biochemistry
* Creatinine \> 1.3 x ULN
* Aspartate aminotransferase (AST) \> 2.5 x ULN
* Alanine aminotransferase (ALT) \> 2.5 x ULN Urinalysis
* Abnormal dipstick confirmed by microscopy
3. Reported high-risk behaviour for HIV infection. High-risk behaviour for HIV-1 infection is defined as follows. Within the previous 6 months the volunteer has:

* Had unprotected vaginal or anal sex with a known HIV-infected person or a casual partner (i.e., no continuing, established relationship)
* Engaged in sex work for money or drugs
* Used injection drugs
* Acquired one of the following sexually transmitted disease (STD); Chlamydia, gonorrhoea and syphilis.
4. Confirmed HIV-1 or HIV-2 infection.
5. If female, pregnant or planning a pregnancy within 6 weeks after last vaccination; or lactating.
6. 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 within the previous 14 days or planned receipt within14 days after vaccination with Investigational Product.
7. Receipt of blood transfusion or blood products within the previous 6 months.
8. Participation in another clinical trial of an Investigational Product currently, within the previous 3 months or expected participation during this study.
9. Receipt of any investigational HIV vaccine within the last 6 years.
10. History of severe or very severe local or systemic reactogenicity events, or history of severe or very severe allergic reactions.
11. Confirmed diagnosis of hepatitis B virus (surface antigen, HBsAg), hepatitis C virus (HCV antibodies) or active syphilis.
12. Smallpox vaccination within the previous 3 years (smallpox vaccination prior to 3 years should be documented but is not an exclusion criterion).
13. Major psychiatric illness including any history of schizophrenia or severe psychosis, bipolar disorder requiring therapy, suicidal attempt or ideation in the previous 3 years.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tomas Hanke

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Lucy Dorrell

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

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Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxon, United Kingdom

Site Status

Countries

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United Kingdom

References

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Moyo N, Borthwick NJ, Wee EG, Capucci S, Crook A, Dorrell L, Hanke T. Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens. PLoS One. 2017 Jul 18;12(7):e0181382. doi: 10.1371/journal.pone.0181382. eCollection 2017.

Reference Type DERIVED
PMID: 28719652 (View on PubMed)

Borthwick N, Lin Z, Akahoshi T, Llano A, Silva-Arrieta S, Ahmed T, Dorrell L, Brander C, Murakoshi H, Takiguchi M, Hanke T. Novel, in-natural-infection subdominant HIV-1 CD8+ T-cell epitopes revealed in human recipients of conserved-region T-cell vaccines. PLoS One. 2017 Apr 27;12(4):e0176418. doi: 10.1371/journal.pone.0176418. eCollection 2017.

Reference Type DERIVED
PMID: 28448594 (View on PubMed)

Hayton EJ, Rose A, Ibrahimsa U, Del Sorbo M, Capone S, Crook A, Black AP, Dorrell L, Hanke T. Safety and tolerability of conserved region vaccines vectored by plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind phase I trial. PLoS One. 2014 Jul 9;9(7):e101591. doi: 10.1371/journal.pone.0101591. eCollection 2014.

Reference Type DERIVED
PMID: 25007091 (View on PubMed)

Other Identifiers

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HIV-CORE 002

Identifier Type: -

Identifier Source: org_study_id