Dendritic Cell Vaccine in HIV-1 Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Felipe Garcia, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT00402142
First received: November 17, 2006
Last updated: February 25, 2014
Last verified: February 2014

November 17, 2006
February 25, 2014
November 2006
December 2011   (final data collection date for primary outcome measure)
Comparison of steady state viremia (so-called viral set point) after 6-12 months after vaccination with viremia before HAART. [ Time Frame: 6 and 12 months ] [ Designated as safety issue: Yes ]
Comparison of steady state viremia (so-called viral set point) after 6-12 months after vaccination with viremia before HAART.
Complete list of historical versions of study NCT00402142 on ClinicalTrials.gov Archive Site
  • Proportion with evidence of HIV-specific CTL comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy. [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Proportion with evidence of HIV-specific T-cell proliferative response comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy. [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Proportion with evidence of HIV-specific neutralizing activity of serum comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy. [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • HIV-1 specific CTL responses in lymphoid tissue [ Time Frame: 0 and 6 months ] [ Designated as safety issue: No ]
  • DC Migration [ Time Frame: 0 and 2 weeks ] [ Designated as safety issue: No ]
  • Viral load in semen and vaginal secretions [ Time Frame: 0 and 6 months ] [ Designated as safety issue: No ]
  • Proportion with evidence of HIV-specific CTL comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy.
  • Proportion with evidence of HIV-specific T-cell proliferative response comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy.
  • Proportion with evidence of HIV-specific neutralizing activity of serum comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy.
  • HIV-1 specific CTL responses in lymphoid tissue
  • DC Migration
  • Viral load in semen and vaginal secretions
Not Provided
Not Provided
 
Dendritic Cell Vaccine in HIV-1 Infection
Phase II Study of Autologous Myeloid Dendritic Cells as a "Cellular Adjuvant" for a Therapeutic HIV-1 Vaccine in Early Stage HIV-1+ Patients (DCV-2).
  1. To study the efficacy of a therapeutic HIV vaccine consisting of autologous myeloid dendritic cells pulsed ex vivo with high doses of inactivated autologous HIV-1, in HIV-1 infected patients in a very early stages of the disease (CD4 > 450 x 10 6 /L).
  2. To analyze the HIV-1 humoral and cellular immune responses induced by this immune-based therapy.

Our group has reported recently the first human trial of 4 therapeutic immunizations at six-week intervals with autologous monocyte-derived dendritic cells (MD-DC) loaded with heat-inactivated autologous HIV in 12 HIV infected patients who had been receiving highly active antiretroviral therapy (HAART) since early chronic infection. Autologous HIV was concentrated from plasma (1,500 ml) obtained by plasmapheresis after a 3-month HAART interruption (STOP1) performed 78 weeks before therapeutic immunizations, and HAART was discontinued again (STOP2) after therapeutic immunization. There was a decrease of set-point plasma viral load (PVL) >= 0.5 log after 24 weeks off HAART in 4 out of 12 patients. In addition, we observed a significant lengthening in mean doubling time of PVL rebound (p= 0.01), and significant decreases in the area under the curve of PVL rebound (p= 0.02) and in the mean peak PVL (p= 0.004) during the 12 weeks after STOP 2 compared with STOP1. This virological response was associated with a weak but significant increase in HIV-1 specific CD4 lymphoproliferative response, and with changes in HIV-1 specific CD8+ T-cell responses in peripheral blood and in lymphoid CTL cells after immunization. In lymphoid tissue, we also observed a trend towards a better control of HIV-1 replication coupled with an increase of CD4+ and CTL cells. No significant virological or immunological changes occurred in controls. We show that a therapeutic vaccine with autologous MD-DC pulsed with heat inactivated autologous HIV-1 is feasible, safe and well tolerated and elicited weak and transient cellular immune responses against HIV, associated with a partial and transient control of HIV replication in some patients.

we hypothesized that a DC vaccine pulsed with higher amount of autologous virus obtained by culture could be more effective than the vaccine we used.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
HIV Infections
  • Biological: Dendritic cell vaccine
    107 DC subcutaneous 3 doses every 2 weeks
  • Biological: dendritic cell vaccine
    107 DC subcutaneous 3 doses every 2 weeks
  • Biological: non pulsed dendritic cell untreated patients
    107 DC subcutaneous 3 doses every 2 weeks
  • Biological: pulsed dendritic cell vaccine
    107 DC subcutaneous 3 doses every 2 weeks
  • Biological: non pulsed dendritic cell vaccine
    107 DC subcutaneous 3 doses every 2 weeks
  • Active Comparator: Pulsed dendritic cells untreated patients
    Untreated patients receiving a dendritic cell based vaccine pulsed with autologous heat iactivated virus
    Interventions:
    • Biological: Dendritic cell vaccine
    • Biological: dendritic cell vaccine
  • Placebo Comparator: non pulsed dendritic cells untreated patients
    Intervention: Biological: non pulsed dendritic cell untreated patients
  • Active Comparator: pulsed dendritic cell treated patient
    treated patients will be immunized with a dendritic cell vaccine pulsed with heat inactivated autologous virus immediately before art interruption
    Intervention: Biological: pulsed dendritic cell vaccine
  • Active Comparator: pulsed dendritic cell in treated patients
    patients will be immunized with a dendritic cell vaccine pulsed with heat inactivted autologous virus immediately after interruption of art
    Intervention: Biological: dendritic cell vaccine
  • Placebo Comparator: non pulsed dendritic cells
    Intervention: Biological: non pulsed dendritic cell vaccine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
December 2011
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Confirmed HIV infection
  • CD4 > 450 x 10 6 /L
  • baseline VL >10,000 c/ml before any HAART
  • Part I, patients off HAART at least during 6 months
  • Part II, Patients on HAART with PVL < 200 copies/ml at least during 6 months
  • Written informed consent .

Exclusion Criteria:

  • Patients with failure to HAART
  • Patients with B or C symptoms (CDC classification 1993).
  • Age < 18 years old.
  • Pregnant or breastfeeding women
  • Patients with baseline creatinin > 2.5 mg/dl
  • Patients with baseline GOT/GPT > 250 UI/L
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT00402142
DCV-02/MANON07
Yes
Felipe Garcia, Hospital Clinic of Barcelona
Hospital Clinic of Barcelona
Not Provided
Principal Investigator: Felipe García, MD, PhD Hospital Clínic
Hospital Clinic of Barcelona
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP