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

University of Oxford

Status and phase: Terminated; Phase 1

Conditions: HIV-1

Treatments: Biological: MVA.HIVconsv low dose; Other: Placebo high dose; Other: Placebo low dose; Biological: MVA.HIVconsv high dose

Study type: Interventional

Funder types: Other

Identifiers

NCT01024842

HIV-CORE 001

Details and patient eligibility

About

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.

Enrollment: 19 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

• Women of child-bearing age must not be pregnant, 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 third 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 third immunisation.

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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19 participants in 4 patient groups, including a placebo group

Low dose vaccinees

Experimental group

Description:

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

Treatment:

Biological: MVA.HIVconsv low dose

High dose vaccinees

Experimental group

Description:

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

Treatment:

Biological: MVA.HIVconsv high dose

Low dose placebo

Placebo Comparator group

Description:

Individuals will receive three intramuscular injections of low dose placebo

Treatment:

Other: Placebo low dose

High dose placebo

Placebo Comparator group

Description:

Individuals will receive three intramuscular injections of high dose placebo

Treatment:

Other: Placebo high dose