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

Purpose

ChAd-MVA.HIVconsv-BCN01 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:

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

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 ]
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. ] [ 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 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. ] [ Designated as safety issue: No ]
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. ] [ 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:	24
Study Start Date:	October 2012
Estimated Study Completion Date:	June 2015
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 0-24 week prime/boost regimen (ARM A) 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) 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

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).

Eligibility

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

Criteria

Inclusion Criteria:

Male or female, aged 18-60 years
Confirmed HIV-1 seropositive documented in the past 6 months (by acute antiretroviral syndrome, p24 antigenemia and/or ELISA seroconversion)
Willing and able to give written informed consent for participation in the study
Willing and able to adhere to an effective HAART regimen for the duration of the study
CD4 cell count > 350 cells/ml at screening and at the preceding clinic visit
No new AIDS-defining diagnosis or progression of HIV-related disease.
Haematological and biochemical laboratory parameters as follows: Haemoglobin > 10g/dl, Platelets > 100.000/dl, ALT ≤ 2.5 x ULN, Creatinine ≤ 1.3 x ULN
Serology: negative for hepatitis B surface antigen OR HbsAg positive with HBV DNA < 1000 copies/ml; negative for hepatitis C antibodies OR confirmed clearance of HCV infection (spontaneous or following treatment); negative syphilis serology or documented adequate treatment of syphilis if positive EIA IgG or TPHA
Available for follow up for duration of study (screening + 72 weeks) and willing to comply with the protocol requirements
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:

Confirmed HIV-2 seropositive
Positive pregnancy test
Presence of NRTI mutation in the screening genotype
Participation in another clinical trial within 12 weeks of study entry
History of autoimmune disease other than HIV-related auto-immune disease.
History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study
History of anaphylaxis or severe adverse reaction to vaccines
Previous immunisation with any experimental immunogens
Receipt of blood products within 6 months of study entry
Treatment for cancer or lymphoproliferative disease within 1 year of study entry
Receipt of vaccines other than Hepatitis B vaccine within 2 weeks of study entry or planned receipt within 2 weeks of vaccination
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
Current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01712425

Locations

Spain
Germans Trias i Pujol Hospital	Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Beatriz Mothe, MD,PhD 93 465 63 74 bmothe@irsicaixa.es
Principal Investigator: Beatriz Mothe, MD,PhD
Clinic de Barcelona Hospital	Recruiting
Barcelona, Spain, 08036
Contact: Josep Maria Miró, MD,PhD 93 227 54 00 jmmiro@clinic.ub.es
Principal Investigator: Josep Maria Miró, MD,PhD

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:	April 18, 2013
Health Authority:	Spain: Ministry of Health

Keywords provided by IrsiCaixa:

vaccine
recently HIV-1 infected individuals

ClinicalTrials.gov processed this record on May 19, 2013