Novel Interventions in HIV-1 Infection

NCT01130376 | Terminated Phase 1 DMC

• 3 other identifiers: CRO930G05019572008-000575024
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV-1 Infection

Keywords

Immune based therapy; Therapeutic vaccination; cytokine therapy; HIV therapeutic vaccine

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• The secondary immunological outcomes will be percentage change from baseline to study time point in defined cellular immune responses.

  weekly

Study Arms (3)

Vaccine and cytokines

EXPERIMENTAL

Day 0: Patients receive GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injection. Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections. Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC. Further vaccine boosters are given on day 42 and day 84. GTU-MultiHIV B clade vaccine 1mg/ml being administered as 10 intradermal injections of 100 µl/injection.

Biological: GTU-MultiHIV B clade vaccine1mg; Drug: Interleukin-2; Drug: GM-CSF; Drug: Growth Hormone

Vaccine alone

ACTIVE COMPARATOR

Day 0: Patients are given GTU-MultiHIV B clade vaccine 1mg/ml administered as 10 intradermal injections of 100 µl/injections. Day 42: GTU-MultiHIV B clade vaccine as day 0. Day 84: GTU-MultiHIV B clade vaccine as day 0.

Biological: GTU-MultiHIV B clade vaccine1mg

Cytokines alone

ACTIVE COMPARATOR

Day 7-11: One week following this, patients receive a 5 day course of Cytokines: Aldesleukin (IL-2) Novartis UK (BD; 8 hours apart) 5 million units administered by SC injection. Sargramostim (GM-CSF) - Leukine™, Berlex Seattle US 150ug SC once daily 4 hours from rhIL-2 injections. Day 14-18: The following week, patients rhGH (Saizen™, Serono International, Geneva, Switzerland) 4mg/day self-administered SC.

Drug: Interleukin-2; Drug: GM-CSF; Drug: Growth Hormone

Interventions

GTU-MultiHIV B clade vaccine1mg BIOLOGICAL

Dose given is 1mg/ml administered as 10 intradermal injections of 100 µl/injection distributed as 5 intradermal injections /left and right arm

Vaccine alone; Vaccine and cytokines

Interleukin-2 DRUG

5 Million Units administered twice daily for 5 days by subcutaneous injection on days 7, 8, 9, 10, and 11 after first vaccination. .

Also known as: Aldesleukin, Proleukin

Cytokines alone; Vaccine and cytokines

GM-CSF DRUG

150 ug administered subcutaneously once daily 4 hours from IL-2 injections

Also known as: Sargramostim, Leukine

Cytokines alone; Vaccine and cytokines

Growth Hormone DRUG

4mg/day will be self administered by Subcutaneous injection for 5 days on days 14, 15, 16, 17 and 18 following first vaccination

Also known as: Serono International, Geneva, Switzerland

Cytokines alone; Vaccine and cytokines

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead
• Medical Research Council: collaborator

Study Sites (1)

St. Stephen's AIDS Trust

London, SW10 9NH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25454870 DERIVED

Related Links

• research team web page

MeSH Terms

Interventions

Interleukin-2; aldesleukin; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim; Growth Hormone

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Nesrina Imami, MD/PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2010
• First Posted: May 26, 2010
• Study Start: September 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: September 4, 2013

Record last verified: 2012-09

Locations

GB (1)