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

NCT01712425 | Completed Phase 1

• 2 other identifiers: ChAd-MVA.HIVconsv-BCN012011-000846-39
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV

Keywords

vaccine; recently HIV-1 infected individuals

Outcome Measures

Primary Outcomes (3)

• Grade 3 or 4 local reaction

  The proportion of volunteers who develop a grade 3 or 4 local reaction

  Up to 24 weeks

• Grade 3 or 4 systemic reaction

  The proportion of volunteers who develop a grade 3 or 4 systemic reaction

  Up to 24 weeks

• Serious adverse event, including laboratory abnormalities.

  The proportion of volunteers who develop a serious adverse event, including laboratory abnormalities.

  Up to 24 weeks

Secondary Outcomes (5)

• HIV-specific CD8+ T cell responses

  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

  Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.

• Lymphocyte activation marker HLADR+CD38+

  Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.

• Integrated and unintegrated viral HIV-1 DNA in PBMCs.

  Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.

• Viral suppressive capacity of CD8+ T cells in vitro

  Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.

Study Arms (4)

0-24 week prime/boost regimen (ARM A)

EXPERIMENTAL

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

0-8 week prime/boost regimen (ARM B)

EXPERIMENTAL

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

Arm A control (ARM C)

NO INTERVENTION

Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. Follow-up as in Arm A.

Arm B control (ARM D)

NO INTERVENTION

Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. Follow-up as in Arm B.

Interventions

0-24 week prime/boost regimen BIOLOGICAL

ChAdV63.HIVcons (5x10\^10 vp) and MVA.HIVconsv (2x10\^8 pfu) HIV-1 vaccines, delivered intramuscularly

Also known as: ARM A

0-24 week prime/boost regimen (ARM A)

0-8 week prime/boost regimen BIOLOGICAL

ChAdV63.HIVcons (5x10\^10 vp) and MVA.HIVconsv (2x10\^8 pfu) HIV-1 vaccines, delivered intramuscularly

Also known as: ARM B

0-8 week prime/boost regimen (ARM B)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Cluster of differentiation 4 (CD4)+ T 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, alanine aminotransferase (ALT) ≤ 2.5 x ULN, Creatinine ≤ 1.3 x upper limit of normal (ULN)
• 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)
• 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.

You may not qualify if:

• Confirmed HIV-2 seropositive
• Positive pregnancy test
• Presence of Nucleos(t)ide Reverse Transcriptase Inhibitors (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

Sponsors & Collaborators

• IrsiCaixa: lead
• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: collaborator
• Hospital Clinic of Barcelona: collaborator
• HIVACAT: collaborator
• University of Oxford: collaborator

Study Sites (2)

Germans Trias i Pujol Hospital

Badalona, Barcelona, 08916, Spain

Location

Clinic de Barcelona Hospital

Barcelona, 08036, Spain

Location

Related Publications (1)

• Mothe B, Manzardo C, Sanchez-Bernabeu A, Coll P, Moron-Lopez 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, Miro 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.

  PMID: 31312806 DERIVED

MeSH Terms

Interventions

PRIME protocol

Study Officials

• Christian Brander, PhD

  Institut de Recerca de la Sida IrsiCaixa-HIVACAT

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2012
• First Posted: October 23, 2012
• Study Start: October 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: May 7, 2024

Record last verified: 2024-05

Locations

ES (2)