Novel Interventions in HIV-1 Infection

HIV-1 Infection Clinical Trial

— IMIRC1003  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01130376
• Other study ID #: CRO930
• Secondary ID: G05019572008-000
• Status: Terminated
• Phase: Phase 1
• First received: May 25, 2010
• Last updated: September 2, 2013
• Start date: September 2009
• Est. completion date: October 2011

Study information

• Verified date: September 2012
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented HIV-1 positive result.

• Stable on HAART.

• Two screening viral loads of <50 cps/ml on 2 consecutive occasions at least one month apart.

• CD4 T cell count of >400 cells/ul.

• Nadir CD4 T cell count of >200 cells/ul.

• Over 18 years of age.

• Willing and able to provide informed consent.

• Female subjects must not be pregnant or lactating.

• Subjects must be using adequate double barrier method of contraception as appropriate.

Exclusion Criteria:

• Prior therapeutic vaccination.

• Acute illness within 2 weeks of the start of the study.

• Prior immunomodulatory therapy (e.g. IL-2, rhGH, GCSF, GM-CSF, HU)

• Receiving immunosuppressive medication (e.g. Steroids)

• Participation in other vaccine trials currently

• Patients with diabetes mellitus type 2

• Patients with cardiac abnormalities

• Patients with pre-existing autoimmune disease

• Patients with active neoplasia

• Patients with evidence of any progression or recurrence of an underlying intra-cranial lesion

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• HIV-1 Infection

Intervention

Biological:
• GTU-MultiHIV B clade vaccine1mg
Dose given is 1mg/ml administered as 10 intradermal injections of 100 µl/injection distributed as 5 intradermal injections /left and right arm

Drug:
• Interleukin-2
5 Million Units administered twice daily for 5 days by subcutaneous injection on days 7, 8, 9, 10, and 11 after first vaccination. .
• GM-CSF
150 ug administered subcutaneously once daily 4 hours from IL-2 injections
• Growth Hormone
4mg/day will be self administered by Subcutaneous injection for 5 days on days 14, 15, 16, 17 and 18 following first vaccination

Locations

Country	Name	City	State
United Kingdom	St. Stephen's AIDS Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Medical Research Council

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Weekly	Yes
Secondary	The secondary immunological outcomes will be percentage change from baseline to study time point in defined cellular immune responses.		weekly	No

External Links

•   research team web page