Safety and Immunogenicity of MVA.HIVconsv in HIV-1 Seropositive Adults on HAART

NCT01024842 | Terminated Phase 1 DMC

• 1 other identifier: HIV-CORE 001
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

In this study, the novel vaccine candidate, MVA.HIVconsv, will be tested for safety, tolerability and immunogenicity in HIV-1-seropositive subjects receiving effective antiretroviral therapy. MVA.HIVconsv will be tested as a single vaccine modality, as a prelude to testing in a heterologous viral vector boost regimen which will include a replication-defective simian adenovirus expressing the same immunogen.

Conditions

HIV-1

Outcome Measures

Primary Outcomes (1)

• The proportion of volunteers who develop a grade 3 or 4 local or systemic reactions

  Actively collected data throughout the study until 6 months after the last vaccination

Secondary Outcomes (8)

• A descriptive summary of grade 3 or 4 local and systemic events, including laboratory abnormalities

  Actively collected data throughout the study until 6 months after the last vaccination

• A descriptive summary of serious adverse events, including laboratory abnormalities

  Actively collected data throughout the study until 6 months after the last vaccination

• The proportion of volunteers who develop CD8+ T cell responses to a new HIV-1 epitope, as determined by IFN-γ ELISPOT assay

  Screen (≤ day -28); Day 0; Day 14; Day 28; Day 42; Day 56; Day 84; Day 112; Day 182; Final visit (day 266 / early termination)

• The proportion of volunteers in whom the magnitude of CD8+ T cell responses to HIVconsv peptides increases by ≥ 3-fold, as determined by IFN-γ ELISPOT assay

  Screen (≤ day -28); Day 0; Day 14; Day 28; Day 42; Day 56; Day 84; Day 112; Day 182; Final visit (day 266 / early termination)

• Evaluation of the effect of MVA.HIVconsv vaccinations on viral suppressive capacity of CD8+ T cells in vitro, using a novel flow cytometric assay

  Screen (≤ day -28); Day 0; Day 14; Day 28; Day 42; Day 56; Day 84; Day 112; Day 182; Final visit (day 266 / early termination)

Study Arms (4)

Low dose vaccinees

EXPERIMENTAL

Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10\^8 pfu.

Biological: MVA.HIVconsv low dose

High dose vaccinees

EXPERIMENTAL

Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10\^8 pfu.

Biological: MVA.HIVconsv high dose

Low dose placebo

PLACEBO COMPARATOR

Individuals will receive three intramuscular injections of low dose placebo

Other: Placebo low dose

High dose placebo

PLACEBO COMPARATOR

Individuals will receive three intramuscular injections of high dose placebo

Other: Placebo high dose

Interventions

MVA.HIVconsv low dose BIOLOGICAL

Three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10\^8 pfu at week 0, 4 and 12.

Low dose vaccinees

Placebo low dose OTHER

Three intramuscular injections of placebo alone (200ul) at week 0, 4 and 12.

Low dose placebo

MVA.HIVconsv high dose BIOLOGICAL

Three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10\^8 pfu at week 0, 4 and 12.

High dose vaccinees

Placebo high dose OTHER

Three intramuscular injections of placebo alone (800ul) at week 0, 4 and 12.

High dose placebo

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
• Willing and able to give written informed consent for participation in the study
• Treated continuously with a combination of 3 or more antiretroviral agents for the preceding 12 months
• Willing and able to adhere to an effective ART regimen for the duration of the study (switching from current regimen is allowed if for reasons of tolerability or toxicity)
• CD4 cell count \> 350 cells/μl at screening and at the preceding clinic visit
• Plasma viral load \< 50 copies / ml at screening and at the preceding clinic visit
• No new AIDS-defining diagnosis or progression of HIV-related disease in the preceding 6/12 months
• Haematological and biochemical laboratory parameters as follows:
• Haemoglobin \> 10g/dl
• Platelets \> 100,000/μl
• 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 + 38 weeks) and willing to comply with the protocol requirements

You may not qualify if:

• Confirmed HIV-2 seropositive
• Positive pregnancy test
• Participation in another clinical trial within 12 weeks of study entry
• History of autoimmune disease other than HIV-related auto-immune disease which has resolved with ART
• 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
• History of alcohol or drug dependency which could, in the opinion of the investigators, impair the subject's ability to complete the study
• Previous immunisation with a recombinant MVA vaccine
• Immunisation with any experimental immunogens within 6 months of study entry
• Receipt of blood products or immunoglobulins 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

• University of Oxford: lead
• Medical Research Council: collaborator

Study Sites (2)

Weatherall Institute of Molecular Medicine

Oxford, Oxons, OX3 9DS, United Kingdom

Location

Oxford Genitourinary Medicine

Oxford, Oxon, OX3 7LJ, United Kingdom

Location

Related Publications (1)

• Hancock G, Moron-Lopez S, Kopycinski J, Puertas MC, Giannoulatou E, Rose A, Salgado M, Hayton EJ, Crook A, Morgan C, Angus B, Chen F, Yang H, Martinez-Picado J, Hanke T, Dorrell L. Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects. J Int AIDS Soc. 2017 May 19;20(1):21171. doi: 10.7448/IAS.20.1.21171.

  PMID: 28537062 DERIVED

Study Officials

• Tomas Hanke

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Andrew McMichael

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Lucy Dorrell

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 3, 2009
• Study Start: December 1, 2009
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: June 8, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (2)