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

NCT01151319 | Completed Phase 1 DMC

• 1 other identifier: HIV-CORE 002
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

HIV-1 Infections

Outcome Measures

Primary Outcomes (1)

• Safety

  Proportion of volunteers who develop a grade 3 or 4 local reaction.

  Actively collected data throughout the study until 6 months after the last vaccination

Secondary Outcomes (2)

• Immunogenicity

  Samples will be collected at every visit pre- and post vaccination

• Immunogenicity

  Stage 1; screen, 0, 1, 2, 4, 8, 16, 28 wk. Stage 2; screen, 0, 1, 2, 4, 8, 9, 12, 20, 28 wk. Stage 3; screen, 1, 8, 12, 13, 14, 20, 21, 22, 28 wk. Stage 4; screen, 0, 8, 12, 13, 16, 17, 18, 24, 28 wk post vac. Stage 2 & 3: 6,12,24 mth after last vaccine

Study Arms (7)

Stage 1.

EXPERIMENTAL

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

Biological: ChAdV63.HIVconsv low dose.

Stage 2

EXPERIMENTAL

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.

Biological: ChAdV63.HIVconsv high dose.; Biological: MVA.HIVconsv

Stage 3

EXPERIMENTAL

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.

Biological: ChAdV63.HIVconsv high dose.; Biological: pSG2.HIVconsv; Biological: MVA.HIVconsv

Stage 4

EXPERIMENTAL

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).

Biological: ChAdV63.HIVconsv high dose.; Biological: pSG2.HIVconsv; Biological: MVA.HIVconsv

Stage 2 Placebo

PLACEBO COMPARATOR

Time-course matched to vaccinations (n=2)

Other: Placebo

Stage 3 placebo

PLACEBO COMPARATOR

Time-course matched to vaccinations (n=2)

Other: Placebo

Stage 4 placebo

PLACEBO COMPARATOR

Time-course matched to vaccinations (n=2)

Other: Placebo

Interventions

ChAdV63.HIVconsv low dose. BIOLOGICAL

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

Stage 1.

ChAdV63.HIVconsv high dose. BIOLOGICAL

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

Stage 2; Stage 3; Stage 4

pSG2.HIVconsv BIOLOGICAL

DNA at 4mg per dose.

Stage 3; Stage 4

MVA.HIVconsv BIOLOGICAL

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

Stage 2; Stage 3; Stage 4

Placebo OTHER

Phosphate buffered saline

Stage 2 Placebo; Stage 3 placebo; Stage 4 placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males or females, as assessed by a medical history, physical examination and laboratory tests.
• Aged at least 18 years on the day of screening and no greater than 50 years on the day of the 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, the volunteer has understood the information provided. Written informed consent must be given before any study-related procedures are performed.
• Willing to undergo HIV-1 testing, HIV-1 counselling and receive HIV-1 test results.
• 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.
• 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.
• Willing to forgo donations of blood during the study.

You may not qualify if:

• 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.
• 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
• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxon, OX3 9DZ, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 28719652 DERIVED

• 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.

  PMID: 28448594 DERIVED

• 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.

  PMID: 25007091 DERIVED

Study Officials

• Tomas Hanke

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Lucy Dorrell

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2010
• First Posted: June 28, 2010
• Study Start: October 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 30, 2014

Record last verified: 2014-04

Locations

GB (1)