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

HIV-1 Clinical Trial

Official title:

HIV-CORE 001 - A Randomised Placebo-controlled Study to Evaluate the Safety and Immunogenicity of a Candidate HIV-1 Vaccine, MVA.HIVconsv, Delivered by Intramuscular Needle Injection to HIV-1 Seropositive Adult Subjects Receiving Antiretroviral Therapy (ART).

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01024842
• Other study ID #: HIV-CORE 001
• Status: Terminated
• Phase: Phase 1
• First received: December 1, 2009
• Last updated: June 7, 2016
• Start date: December 2009
• Est. completion date: November 2013

Study information

• Verified date: June 2016
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1

Intervention

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

Other:
• Placebo low dose
Three intramuscular injections of placebo alone (200ul) at week 0, 4 and 12.

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

Other:
• Placebo high dose
Three intramuscular injections of placebo alone (800ul) at week 0, 4 and 12.

Locations

Country	Name	City	State
United Kingdom	Oxford Genitourinary Medicine	Oxford	Oxon
United Kingdom	Weatherall Institute of Molecular Medicine	Oxford	Oxons

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	Medical Research Council

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	A descriptive summary of serious adverse events, including laboratory abnormalities		Actively collected data throughout the study until 6 months after the last vaccination	Yes
Secondary	The proportion of volunteers who develop CD8+ T cell responses to a new HIV-1 epitope, as determined by IFN-? 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)	No
Secondary	The proportion of volunteers in whom the magnitude of CD8+ T cell responses to HIVconsv peptides increases by = 3-fold, as determined by IFN-? 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)	No
Secondary	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)	No
Secondary	Magnitude and phenotype, including but not limited to activation status, of HIV-1-specific CD8+ T cell populations identified by tetramer staining before and after vaccination, in selected volunteers with appropriate HLA class I alleles.		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)	No
Secondary	PBMC will be stored for other exploratory assays to characterise vaccine-expanded T cell populations such as IL-10 secretion and CFSE proliferation assays.		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)	No
Secondary	Serum and plasma will be stored for investigation of binding and neutralising antibodies to vaccinia and of pro-inflammatory cytokines.		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)	No