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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01712425
Recruitment Status : Completed
First Posted : October 23, 2012
Last Update Posted : April 29, 2016
Sponsor:
Collaborators:
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Hospital Clinic of Barcelona
HIVACAT
University of Oxford
Information provided by (Responsible Party):
IrsiCaixa

Tracking Information
First Submitted Date  ICMJE October 4, 2012
First Posted Date  ICMJE October 23, 2012
Last Update Posted Date April 29, 2016
Study Start Date  ICMJE October 2012
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2012)
  • Grade 3 or 4 local reaction [ Time Frame: Up to 24 weeks ]
    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 ]
    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 ]
    The proportion of volunteers who develop a serious adverse event, including laboratory abnormalities.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2014)
  • HIV-specific CD8+ T cell responses [ Time Frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination. ]
    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. ]
    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. ]
    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. ]
    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. ]
    Viral suppressive capacity of CD8+ T cells in vitro using a flow cytometric assay at selected timepoints according to first immunogenicity results
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2012)
  • HIV-specific CD8+ T cell responses [ Time Frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination. ]
    The proportion of individuals who increase by ≥ 3-fold HIV-specific CD8+ T cell responses. Responses to the HIVconsv and outside the vaccine insert will be assessed.
  • 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. ]
    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. ]
    Lymphocyte activation marker HLADR+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. ]
    Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs 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. ]
    Viral suppressive capacity of CD8+ T cells in vitro using a flow cytometric assay at selected timepoints according to first immunogenicity results
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Immunogenicity of ChAdV63.HIVconsv and MVA.HIVconsv Candidate HIV-1 Vaccines in Recently HIV-1 Infected Individuals
Official Title  ICMJE 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)
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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
    Intervention: Biological: 0-24 week prime/boost regimen
  • 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
    Intervention: Biological: 0-8 week prime/boost regimen
  • 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.
Publications * Mothe B, Manzardo C, Sanchez-Bernabeu A, Coll P, Morón-López S, Puertas MC, Rosas-Umbert M, Cobarsi P, Escrig R, Perez-Alvarez N, Ruiz I, Rovira C, Meulbroek M, Crook A, Borthwick N, Wee EG, Yang H, Miró JM, Dorrell L, Clotet B, Martinez-Picado J, Brander C, Hanke T. Therapeutic Vaccination Refocuses T-cell Responses Towards Conserved Regions of HIV-1 in Early Treated Individuals (BCN 01 study). EClinicalMedicine. 2019 Jun 5;11:65-80. doi: 10.1016/j.eclinm.2019.05.009. eCollection 2019 May-Jun. Erratum in: EClinicalMedicine. 2020 Jan 10;18:100250.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 29, 2013)
48
Original Estimated Enrollment  ICMJE
 (submitted: October 19, 2012)
20
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01712425
Other Study ID Numbers  ICMJE ChAd-MVA.HIVconsv-BCN01
2011-000846-39 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party IrsiCaixa
Study Sponsor  ICMJE IrsiCaixa
Collaborators  ICMJE
  • Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
  • Hospital Clinic of Barcelona
  • HIVACAT
  • University of Oxford
Investigators  ICMJE
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
PRS Account IrsiCaixa
Verification Date April 2016

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