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
  Purpose
  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.

Condition Intervention Phase
HIV Infections
Biological: Dendritic cell vaccine
Biological: dendritic cell vaccine
Biological: non pulsed dendritic cell untreated patients
Biological: pulsed dendritic cell vaccine
Biological: non pulsed dendritic cell vaccine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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).

Resource links provided by NLM:


Further study details as provided by Hospital Clinic of Barcelona:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 60
Study Start Date: November 2006
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pulsed dendritic cells untreated patients
Untreated patients receiving a dendritic cell based vaccine pulsed with autologous heat iactivated virus
Biological: Dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
Biological: dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
Placebo Comparator: non pulsed dendritic cells untreated patients Biological: non pulsed dendritic cell untreated patients
107 DC subcutaneous 3 doses every 2 weeks
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
Biological: pulsed dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
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
Biological: dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
Placebo Comparator: non pulsed dendritic cells Biological: non pulsed dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402142

Locations
Spain
Hospital Clínic
Barcelona, Spain, 08036
Sponsors and Collaborators
Hospital Clinic of Barcelona
Investigators
Principal Investigator: Felipe García, MD, PhD Hospital Clínic
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Felipe Garcia, Principal investigator, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier: NCT00402142     History of Changes
Other Study ID Numbers: DCV-02/MANON07
Study First Received: November 17, 2006
Last Updated: February 25, 2014
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Hospital Clinic of Barcelona:
HIV Infection
Dendritic cell vaccine
Autologous virus
Heat inactivated
HIV Therapeutic Vaccine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 29, 2014