Ad4HIV
Research type
Research Study
Full title
Ad4HIV: A Phase I Single-Blind randomised trial investigating immunisation strategies using Ad4-EnvCN54, MVA-CN54 and CN54rgp140 combinations in order to maximise antibody responses to Human Immunodeficiency Virus
IRAS ID
186866
Contact name
David Lewis
Contact email
Sponsor organisation
Imperial College London
Eudract number
2016-000052-94
Duration of Study in the UK
2 years, 5 months, 30 days
Research summary
Summary of Research
Ad4HIV is a randomised two part Phase I study that will explore the impact of different boosting options (MVA and protein) for oral Adenovirus serotype 4 vector prime expressing HIV-1 CN54 gp160 (Ad4CN54) designed to optimize systemic and mucosal antibody response.The aim of the study is to test the hypothesis that each of the routes and combination regimens are safe and acceptable. Our main immunological objective will be to evaluate the impact of different boosting options (Ad4, MVA, protein and combinations thereof) to augment systemic and mucosal antibody response following initial Ad4 priming.
This is an adaptive design Phase I trial that will be conducted in two separate parts.
Part 1 is exploratory and designed to select conditions capable of promoting enhanced systemic and mucosal B cell responses in a limited number of volunteers. There will be 8 groups of 6 healthy volunteers (A-H). The vaccine combination regime that meets the pass criteria will be taken forward and used in Part 2 of the Phase I trial.
Part 2, the best regimes from B-D (Ad4-EnvCN54/CN54 rgp140) and F-H (Ad4-EnvCN54/MVA-CN54/CN54 rgp140), if meeting the pass criterion, will be expanded to n=12 (additional n=6) in Part 2. The pass criterion will be 3 participants having a mucosal (rectal) response at the Primary Immunogenicity Endpoint (Week 26). If more than one group meets the pass criterion, then selection will based on total number of responders. In the event that more than one group has the same number of responders, mucosal antibody titre will be used to rank groups to determine which to take forward to Part 2. Should mucosal titers be indistinguishable between groups, then serum antibody levels will be taken into consideration in the selection of groups to progress to Part 2.
This study will assess the safety and immunogenicity of Ad4 vector prime expressing HIV-1 CN54 gp160 (Ad4CN54) and boosted with MVA, protein and combinations thereof. Our primary hypothesis is that oral vaccination using the replicating vector Ad4 will prime systemic and mucosal responses to the HIV-1 envelope glycoprotein.
Summary of Results
The trial assessed various combinations of three investigational vaccines against human immunodeficiency virus (HIV): one which was taken orally as a capsule; and two which were injected into a muscle in the arm. Sixty-eight healthy volunteers were enrolled. The vaccines were safe and well tolerated, and induced antibody and cellular immune responses. The oral vaccine seemed to be effective at stimulating the immune response, and this was further boosted by the injected vaccines. However, none of the combinations induced immune responses that were strong enough to merit further development of the vaccines used.REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
17/EE/0097
Date of REC Opinion
24 May 2017
REC opinion
Further Information Favourable Opinion