Safety and Immunogenicity of ChAdV63.HIVconsv and MVA.HIVconsv Candidate HIV-1 Vaccines in Recently HIV-1 Infected Individuals

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Fundacio Lluita Contra la SIDA
Hospital Clinic of Barcelona
HIVACAT
University of Oxford
Information provided by (Responsible Party):
IrsiCaixa
ClinicalTrials.gov Identifier:
NCT01712425
First received: October 4, 2012
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

The HIVconsv gene was constructed by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. This gene has been inserted into 2 leading non-replicating vaccine vectors: an attenuated chimpanzee adenovirus serotype 63 (ChAdV63) and a modified vaccinia virus Ankara (MVA) to construct the ChAdV63.HIVconsv and MVA.HIVconsv HIV-1 candidate vaccines. The present study is named ChAd-MVA.HIVconsv-BCN01 and it is a phase I, multicenter primary/booster therapeutic vaccination study to evaluate the safety and immunogenicity of ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly according to a 0-8 weeks or a 0-24 weeks schedule to recently HIV-1 infected individuals with early viral suppression 6 months after initiation of Tenofovir/Emtricitabine plus Raltegravir.


Condition Intervention Phase
HIV
Biological: 0-24 week prime/boost regimen
Biological: 0-8 week prime/boost regimen
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Immunogenicity of ChAdV63.HIVconsv and MVA.HIVconsv Candidate HIV-1 Vaccines in Recently HIV-1 Infected Individuals With Early Viral Suppression After Initiation of Antiretroviral Therapy (HAART)

Resource links provided by NLM:


Further study details as provided by IrsiCaixa:

Primary Outcome Measures:
  • Grade 3 or 4 local reaction [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    The proportion of volunteers who develop a grade 3 or 4 local reaction

  • Grade 3 or 4 systemic reaction [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    The proportion of volunteers who develop a grade 3 or 4 systemic reaction

  • Serious adverse event, including laboratory abnormalities. [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    The proportion of volunteers who develop a serious adverse event, including laboratory abnormalities.


Secondary Outcome Measures:
  • HIV-specific CD8+ T cell responses [ Time Frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination. ] [ Designated as safety issue: No ]
    Magnitude and phenotype of HIV-1-specific CD8+ T cell populations , in selected volunteers with appropriate human leukocyte antigen (HLA) class I alleles will be assessed according to first immunogenicity results.

  • Magnitude and phenotype of HIV-1-specific CD8+ T cell populations [ Time Frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination. ] [ Designated as safety issue: No ]
    Magnitude and phenotype of HIV-1-specific CD8+ T cell populations , in selected volunteers with appropriate HLA class I alleles will be assessed according to first immunogenicity results.

  • Lymphocyte activation marker HLADR+CD38+ [ Time Frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination. ] [ Designated as safety issue: No ]
    Lymphocyte activation marker HLA-DR+CD38+ will be assessed at selected timepoints according to first immunogenicity results

  • Integrated and unintegrated viral HIV-1 DNA in PBMCs. [ Time Frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination. ] [ Designated as safety issue: No ]
    Quantification of integrated and unintegrated viral HIV-1 DNA in peripheral blood mononucleated cells (PBMC)s will be determined at selected timepoints according to first immunogenicity results

  • Viral suppressive capacity of CD8+ T cells in vitro [ Time Frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination. ] [ Designated as safety issue: No ]
    Viral suppressive capacity of CD8+ T cells in vitro using a flow cytometric assay at selected timepoints according to first immunogenicity results


Estimated Enrollment: 48
Study Start Date: October 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 0-24 week prime/boost regimen (ARM A)
Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly, 0-24 week prime/boost regimen
Biological: 0-24 week prime/boost regimen
ChAdV63.HIVcons (5x10^10 vp) and MVA.HIVconsv (2x10^8 pfu) HIV-1 vaccines, delivered intramuscularly
Other Name: ARM A
Experimental: 0-8 week prime/boost regimen (ARM B)
Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly, 0-8 week prime/boost regimen
Biological: 0-8 week prime/boost regimen
ChAdV63.HIVcons (5x10^10 vp) and MVA.HIVconsv (2x10^8 pfu) HIV-1 vaccines, delivered intramuscularly
Other Name: ARM B
No Intervention: Arm A control (ARM C)
Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. Follow-up as in Arm A.
No Intervention: Arm B control (ARM D)
Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. Follow-up as in Arm B.

Detailed Description:

It is a Phase I, multicenter primary/booster therapeutic vaccination study to evaluate the safety and immunogenicity of ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly according to a 0-8 weeks or a 0-24 weeks schedule to recently HIV-1 infected individuals with early viral suppression 6 months after initiation of Tenofovir/Emtricitabine plus Raltegravir.

24 patients who meet all eligibility criteria will be enrolled, first 10 individuals will be assigned in the 0-24 week prime/boost regimen (ARM A). The next 10 volunteers will be assigned in the 0-8 week prime/boost regimen (ARM B).Four additional volunteers will be included as 'back-up' and assigned 2 in ARM A and 2 in ARM B to cover a possible 10% of patients who drop-off during the follow-up. Purpose of staging of 2 study arms is just to shorten overall study duration (from screening of first volunteer to 6 months after last immunisation of last volunteer).

Lastly, 24 patients who also meet all eligibility criteria will be enrolled as controls, will also initiate promptly antiretroviral treatment with Tenofovir/Emtricitabine plus Raltegravir but will not receive the investigational vaccines. Control patients will consecutively be assigned to the 0-24w control arm (ARM C 'long control') or 0-8w control arm (ARM D 'short control') until 12 patients per arm are reached. The purpose of the control arms is to have a study population to compare the viral reservoir decay kinetics in the absence of vaccination.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged 18-60 years
  2. Confirmed HIV-1 seropositive documented in the past 6 months (by acute antiretroviral syndrome, p24 antigenemia and/or ELISA seroconversion)
  3. Willing and able to give written informed consent for participation in the study
  4. Willing and able to adhere to an effective HAART regimen for the duration of the study
  5. Cluster of differentiation 4 (CD4)+ T cell count > 350 cells/ml at screening and at the preceding clinic visit
  6. No new AIDS-defining diagnosis or progression of HIV-related disease.
  7. Haematological and biochemical laboratory parameters as follows: Haemoglobin > 10g/dl, Platelets > 100.000/dl, alanine aminotransferase (ALT) ≤ 2.5 x ULN, Creatinine ≤ 1.3 x upper limit of normal (ULN)
  8. Serology: negative for hepatitis B surface antigen OR HbsAg positive with Hepatitis B Virus (HBV)-DNA < 1000 copies/ml; negative for hepatitis C antibodies OR confirmed clearance of Hepatitis C Virus (HCV) infection (spontaneous or following treatment); negative syphilis serology or documented adequate treatment of syphilis if positive enzimeimmunoassay (EIA) Immonoglobulin G (IgG) or Treponema pallidum hemagglutination assay (TPHA)
  9. Available for follow up for duration of study (screening + 72 weeks) and willing to comply with the protocol requirements
  10. Women of child-bearing age must not be pregnant, not be planning a pregnancy or breast-feeding. Sexually active women must be willing to use an approved method of contraception from screening until 4 months after the second immunisation. Sexually active men in heterosexual relationships must be willing to use an approved method of contraception with their partners from screening until 4 months after the second immunisation.

Exclusion Criteria:

  1. Confirmed HIV-2 seropositive
  2. Positive pregnancy test
  3. Presence of Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTI) mutation in the screening genotype
  4. Participation in another clinical trial within 12 weeks of study entry
  5. History of autoimmune disease other than HIV-related auto-immune disease.
  6. History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study
  7. History of anaphylaxis or severe adverse reaction to vaccines
  8. Previous immunisation with any experimental immunogens
  9. Receipt of blood products within 6 months of study entry
  10. Treatment for cancer or lymphoproliferative disease within 1 year of study entry
  11. Receipt of vaccines other than Hepatitis B vaccine within 2 weeks of study entry or planned receipt within 2 weeks of vaccination
  12. Any other prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
  13. Current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents
  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: NCT01712425

Locations
Spain
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916
Clinic de Barcelona Hospital
Barcelona, Spain, 08036
Sponsors and Collaborators
IrsiCaixa
Fundacio Lluita Contra la SIDA
Hospital Clinic of Barcelona
HIVACAT
University of Oxford
Investigators
Study Chair: Christian Brander, PhD Institut de Recerca de la Sida IrsiCaixa-HIVACAT
Principal Investigator: Beatriz Mothe, MD,PhD Institut de Recerca de la Sida IrsiCaixa-HIVACAT
Principal Investigator: Josep Maria Miró, MD,PhD Hospital Clínic i Provincial de Barcelona, HIVACAT
  More Information

No publications provided

Responsible Party: IrsiCaixa
ClinicalTrials.gov Identifier: NCT01712425     History of Changes
Other Study ID Numbers: ChAd-MVA.HIVconsv-BCN01, 2011-000846-39
Study First Received: October 4, 2012
Last Updated: August 6, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by IrsiCaixa:
vaccine
recently HIV-1 infected individuals

ClinicalTrials.gov processed this record on August 18, 2014