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

Phase 1

Completed

• Conditions: HIV-1 Infections
• Interventions: Other: Placebo; Biological: ChAdV63.HIVconsv low dose.; Biological: ChAdV63.HIVconsv high dose.; Biological: pSG2.HIVconsv; Biological: MVA.HIVconsv

• Registration Number: NCT01151319
• Lead Sponsor: University of Oxford

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-06-24
• Study First Submitted QC: 2010-06-25
• Study First Posted: 2010-06-28
• Study Start: 2010-10
• Status Verified: 2014-04
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Last Update Submitted: 2014-04-29
• Last Update Posted: 2014-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stage 4 placebo	Placebo	Time-course matched to vaccinations (n=2)
Stage 3	MVA.HIVconsv	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.
Stage 1.	ChAdV63.HIVconsv low dose.	The first stage will start from a low and well tolerated, but likely less immunogenic dose of ChAdV63.HIVconsv (n=2).
Stage 2	ChAdV63.HIVconsv high dose.	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.
Stage 2	MVA.HIVconsv	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.
Stage 3	ChAdV63.HIVconsv high dose.	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.
Stage 3	pSG2.HIVconsv	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.
Stage 4	ChAdV63.HIVconsv high dose.	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).
Stage 4	pSG2.HIVconsv	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).
Stage 4	MVA.HIVconsv	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).
Stage 2 Placebo	Placebo	Time-course matched to vaccinations (n=2)
Stage 3 placebo	Placebo	Time-course matched to vaccinations (n=2)

Primary Outcome Measures

Name	Time	Method
Safety	Actively collected data throughout the study until 6 months after the last vaccination	Proportion of volunteers who develop a grade 3 or 4 local reaction.

Secondary Outcome Measures

Name	Time	Method
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	Exploration of the efficacy of vaccine-induced CD8+ T cells to suppress HIV-1 replication in vitro.

Trial Locations

Locations (1)

Centre for Clinical Vaccinology and Tropical Medicine; 🇬🇧 Oxford, Oxon, United Kingdom