Novel Interventions in HIV-1 Infection (IMIRC1003)
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ClinicalTrials.gov Identifier: NCT01130376 |
Recruitment Status :
Terminated
(Data from the 12 patients recruited has now been analysed, and it has been determined that it is sufficient to meet the study objectives.)
First Posted : May 26, 2010
Last Update Posted : September 4, 2013
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Tracking Information | ||||
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First Submitted Date ICMJE | May 25, 2010 | |||
First Posted Date ICMJE | May 26, 2010 | |||
Last Update Posted Date | September 4, 2013 | |||
Study Start Date ICMJE | September 2009 | |||
Actual Primary Completion Date | October 2011 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
The primary outcome will be analysis of safety and toxicity data in relation to grade 3 or above laboratory or clinical serious adverse event (SAE) which can be attributed to the treatments given [ Time Frame: Weekly ] | |||
Original Primary Outcome Measures ICMJE | Same as current | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
The secondary immunological outcomes will be percentage change from baseline to study time point in defined cellular immune responses. [ Time Frame: weekly ] | |||
Original Secondary Outcome Measures ICMJE | Same as current | |||
Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Novel Interventions in HIV-1 Infection | |||
Official Title ICMJE | A Randomised, Open Labelled, Phase I, Safety, Toxicity, and Exploratory Immunogenicity Evaluation of Therapeutic Immunisation +/- IL-2, GM-CSF and Growth Hormone in HIV-1 Infected Subjects Receiving Highly Active Anti-retroviral Therapy | |||
Brief Summary | For several years there has been interest in why some people with HIV-1 progress more slowly to disease and have longer survival without Highly Active Antiretroviral Therapy (HAART) than others. The investigators and others have identified a few HIV positive individuals who can control their viral load for many years without HAART, these rare individuals do not lose their HIV-1-specific cellular immune responses, which are very important for controlling viral load. This group is referred to as long-term non-progressors (LTNP). Unlike LTNP the majority of HIV-1 infected individuals are chronic progressors (CP) who do not make effective HIV-1-specific cellular immune responses, even when on HAART. We propose to use a novel DNA vaccine boosted with immune based therapy (cytokines and hormones) to try to regenerate the missing HIV-1-specific cellular immune responses to make chronically infected HIV-1+ persons more like LTNP. By injecting this novel DNA vaccine and immune based therapy into the people who are already infected with HIV-1, the immune system may be stimulated to mount a greater immune response not only to the vaccines but also to real HIV-1 particles and HIV-1-infected cells. |
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Detailed Description | This will be a randomised, Phase I, open label comparative study running for 52 weeks (2 screen visits 2 weeks apart followed by 48 weeks of study). 50 patients will be screened in the initial phase of which 30 clade B infected individuals will be randomised into the study, which will consist of 3 arms: Arm 1 will ascertain vaccine safety and toxicity in the presence of cytokine/hormone therapy. Arm 2 will identify vaccine safety and toxicity. Arm 3 will indicate safety and toxicity of cytokine/hormone therapy. The target patients are chronically HIV-1 clade B infected persons who will have had a nadir CD4 T-cell count of >200 cells/ul blood before they started ART. The current CD4 T-cell count should be >400 cells/ul blood. Patients may have received ART for any length of time, but currently should be receiving NNRTI or boosted-PI based HAART, and have a viral load below the level of detection (50 copies/ml plasma). Patients will be bled on two occasions before commencing IBT regimens, in order to establish baselines, and then at regular intervals thereafter (weeks 0,1,2,4,6,8,12,16,24 and 48). The treatment regimens are consistent with previous findings in animal models which suggest that administration of IL-2 during the antigen-specific T-cell contraction phase of an immune response (between 8 and 15 days post-vaccination) may preserve and lengthen clinically relevant responses. Furthermore studies in man have demonstrated that IL-2 administered before immunisation in ART-treated HIV-1-infected patients does not increase specific lymphoproliferation of T cells. Recent preliminary studies in HIV-1-infected individuals using tetanus vaccines the investigators have shown that IL-2 administered after immunisation may be more effective at inducing sustained tetanus-specific responses than IL-2 administered before immunisation or together with immunisation. The dosages used in this study are based on those used in previous pilot studies of the administration of IL-2 + GM-CSF and rhGH and at these levels the drugs have been shown to have both positive effect on the immune response and demonstrated clinical benefit whilst being at a level which is safe and well tolerated in HIV-1 positive individuals. The dosage of the vaccine was based on a previous study where a dosage of this level has been shown to induce an immune response although this response was transient. In summary the investigators aim to increase the survival of vaccine responses through the administration of cytokines/hormones and boost memory responses with further rounds of immunisation. |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 1 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | HIV-1 Infection | |||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Herasimtschuk A, Downey J, Nelson M, Moyle G, Mandalia S, Sikut R, Adojaan M, Stanescu I, Gotch F, Imami N. Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection. Vaccine. 2014 Dec 5;32(51):7005-7013. doi: 10.1016/j.vaccine.2014.09.072. Epub 2014 Oct 22. | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Terminated | |||
Actual Enrollment ICMJE |
12 | |||
Original Estimated Enrollment ICMJE |
30 | |||
Actual Study Completion Date ICMJE | October 2011 | |||
Actual Primary Completion Date | October 2011 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United Kingdom | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01130376 | |||
Other Study ID Numbers ICMJE | CRO930 G0501957 ( Other Grant/Funding Number: Medical Research Council UK ) 2008-000575024 ( Registry Identifier: EudraCT ) |
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Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | Imperial College London | |||
Original Responsible Party | Gary Roper, Imperial College London | |||
Current Study Sponsor ICMJE | Imperial College London | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Medical Research Council | |||
Investigators ICMJE |
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PRS Account | Imperial College London | |||
Verification Date | September 2012 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |