A Safety and Immunogenicity Study of 3 Doses of Opal Immunotherapy in HIV Infected People
This phase I study is the first step to determine if Opal immunotherapy may have potential utility as a treatment for HIV. Although effective treatments for HIV infection exist, they are limited by the requirement for life-long daily treatment, cost, side effects, and the development of resistance.
There is a need for therapeutic approaches that induce or enhance T-cell immunity to control HIV disease. Overlapping Peptide-pulsed Autologous Cells (Opal) is a technique where autologous peripheral blood mononuclear cells (PBMC) or whole blood is pulsed with sets of overlapping peptides spanning whole proteins of HIV.
Biological: Opal-HIV-Gag(c) Low Dose
Biological: Opal-HIV-Gag(c) Medium dose
Biological: Opal-HIV-Gag(c) High dose
Other: Dimethyl Sulfoxide
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase 1, Dose Escalating, Single Centre, Double Blind Study of the Safety and Immunogenicity of Opal-HIV-Gag Clade C in HIV Positive Subjects|
- Safety [ Time Frame: Several points throughout the 12 week active phase and 12 week and follow up period ] [ Designated as safety issue: Yes ]Examined through treatment-emergent adverse events, vital signs and routine laboratory screening.
- Immunogenicity [ Time Frame: Several points throughout the 12 week active phase and 12 week and follow up period ] [ Designated as safety issue: No ]Immunogenicity will be assessed by ELISpot and other markers of immune response
- Impact on HIV infection [ Time Frame: Several points throughout the 12 week active phase and 12 week and follow up period ] [ Designated as safety issue: Yes ]Assessed by HIV-1 viral load and CD4 T-cell counts.
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||December 2011|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Opal-HIV-Gag(c) administered ex vivo to separated white blood cells on 4 occasions at 4 weekly intervals.
|Biological: Opal-HIV-Gag(c) Low Dose Biological: Opal-HIV-Gag(c) Medium dose Biological: Opal-HIV-Gag(c) High dose|
Placebo Comparator: Diluent
Administered ex vivo to separated white blood cells on 4 occasions at 4 weekly intervals.
|Other: Dimethyl Sulfoxide|
Opal-HIV-Gag(c) is not for direct injection and is administered by ex vivo incubation of whole blood or separated blood components (such as white blood cells or peripheral blood mononuclear cells) and reinfusion.
As a practical alternative to PBMC separation and to optimise vaccine presentation during the ex vivo incubation, a blood cell separation device will be used to separate the whole blood and enrich the white blood cell component. The device processes whole blood in a closed, single use disposable kit. Reconstituted Opal-HIV-Gag(c)or matching placebo will be added to the white blood cells, incubated for one hour and reinfused into the subject. Subjects will receive 4 administrations at 4 weekly intervals. Subjects are followed for 12 weeks after the final administration.
Each dose group will be enrolled sequentially, with a sentinel group for each dose group. Satisfactory safety data from each cohort, reviewed by a Data Safety Monitoring Board, will permit dose escalation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01123915
|St Stephen's Centre, Chelsea and Westminster Foundation Trust|
|London, United Kingdom, SW10 9NH|
|Principal Investigator:||Marta Boffito, MD PhD||St Stephen's AIDS Trust|