A Phase 1/2 interventional study of GTU®-MultiHIV B Clade Vaccine and Sodium chloride BP in HIV, sponsored by Imperial College London. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2016-11-10.
Sponsored by Imperial College London · Phase 1/2, Interventional, and Prevention
CUT*HIVTHER 001 is a randomised placebo-controlled Phase I/II study aimed at exploring the safety and immunogenicity of two different modes of delivery of a GTU® DNA plasmid vaccine (GTU®-multiHIV B clade) in HIV infected volunteers on antiretroviral therapy (ART):
Electroporation (EP) enhanced intramuscular delivery Participants will be randomised 1:1:1 to TC:EP:saline for the purposes of analysis. Half the saline group will receive TC saline and half will receive EP saline.
30 HIV infected male and female volunteers aged 18-45 years, who have been on ART for at least 6 months with 2 or more HIV plasma viral load measurements \< 50 copies HIV RNA/ml prior to enrolment.
The investigational HIV-1 vaccine GTU®-MultiHIV B clade encodes for a MultiHIV antigen which is a synthetic fusion protein consisting of full-length polypeptides of Rev, Nef, Tat, p17 and p24 and containing more than 20 Th and CTL epitopes of protease, reverse transcriptase (RT) and gp160 regions of the HAN2 HIV-1 B clade.
Vaccine is provided in sealed vials at 2mg/ml, and a single 1ml IM injection of 2mg GTU®-MultiHIV DNA IM (into the thigh) is required to deliver a 2mg dose. Individuals in Group 2 will receive a further 0.4mg GTU®-MultiHIV DNA in 0.2ml administered by TC, a novel needle-free method of vaccine delivery.
The investigators are exploring combination regimens with the overall aims of (i) optimising immune responses and (ii) developing safe and well tolerated strategies which will favour the development of T-cell responses that may enhance anti-HIV HIV therapy with the forward looking goal of working towards functional eradication of infection. The investigator proposes to combine the previously used IM and TC methods because preclinical data suggest that the combination of methods will favour the development of CD8 T cell responses. All groups will receive 6.0mg of the vaccine IM given in 3 doses over 12 weeks. Group 1 will receive the 6.0mg IM with electroporation (EP) and Group 2 will receive the 6.0mg IM without EP but together with an additional 1.2mg vaccine TC. The primary immunogenicity endpoint will be to determine whether either intervention group augments the cellular responses to vaccine specific peptides in relation to baseline. It is anticipated that none of subjects receiving saline placebo would have an increase in vaccine specific responses relative to those at baseline. Therefore if the differences between the active groups and saline placebo are sufficiently large, for example 80% responders in a GTU®-MultiHIV DNA active group, \<10% in the control group, this would be significant.
Should the regimes prove safe, acceptable and induce significant immunogenicity then the intention is to move one or both regimes into a larger study powered to determine their potential long-term impact on therapy when used in combination with conventional ARV regimens. Proof of concept that DNA vaccination can induce de novo HIV specific responses that are associated with control of viral replication, would justify further investigation of their use in immunotherapies combined with ART intensification and/or anti-latency drugs.
Imperial College London is the lead sponsor of 824 studies on the registry; 178 are open to participants now.
Of its 9 completed or terminated interventional studies of FDA-regulated products, 6 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Clinically relevant abnormality on history or examination including
History of severe local or general reaction to vaccination defined as
Group 1 (Transcutaneous and Placebo) Participants will receive 1.0ml intramuscular injections of the vaccine Sodium Chloride BP into the upper thigh. Participants will also have a further 0.2ml of Sodium Chloride BP delivered transcutaneously. An area of skin of approximately 4 x 4cm will be photographed and prepared first. During this preparation, the area is shaved to remove the hair, and then superglue is applied to remove the top layer of skin (like waxing). The vaccine is spread onto the skin surface. Once applied, the area is covered with a comfeel bandage, the investigator will ask volunteers to not engage in strenuous exercise, shower, or bathe for 24 hours afterwards.
Other: Sodium chloride BP
Group 2 (Transcutaneous and Active) Participants will receive 1.0ml intramuscular injections of the GTU®-MultiHIV B Clade Vaccine (2 mg/ml) into the upper thigh. Participants will also have a further 0.2ml of the vaccine (2mg/ml) delivered transcutaneously. An area of skin of approximately 4 x 4cm will be photographed and prepared first. During this preparation, the area is shaved to remove the hair, and then superglue is applied to remove the top layer of skin (like waxing). The vaccine is spread onto the skin surface. Once applied, the area is covered with a comfeel bandage, the investigator will ask volunteers to not engage in strenuous exercise, shower, or bathe for 24 hours afterwards.
Biological: GTU®-MultiHIV B Clade Vaccine
Group 3 (Electroporation and Placebo) Participants will receive 1.0ml intramuscular injections of Sodium Chloride BP into the upper thigh using the ICHOR TriGridTM delivery system for intramuscular (TDS-IM) delivery with electroporation. Electroporation (EP) improves the delivery of the product into muscle cells, by delivering an electrical pulse with the injection using a hand held device that is pressed against your thigh. This will cause a muscle twitch with a sharp cramp-like feeling in the thigh lasting a few seconds. Once the procedure is carried out, the muscle will feel sore for up to 72 hours. The investigator will ask volunteers not to engage in any strenuous exercise for at least 24 hours after the procedure.
Other: Sodium chloride BP
Group 4 (Electroporation and Active) Participants will receive 1.0ml intramuscular injections of the GTU®-MultiHIV B Clade Vaccine (2mg/ml) into the upper thigh using the ICHOR TriGridTM delivery system for intramuscular (TDS-IM) delivery with electroporation. Electroporation (EP) improves the delivery of the product into muscle cells, by delivering an electrical pulse with the injection using a hand held device that is pressed against your thigh. This will cause a muscle twitch with a sharp cramp-like feeling in the thigh lasting a few seconds. Once the procedure is carried out, the muscle will feel sore for up to 72 hours. The investigator will ask volunteers not to engage in any strenuous exercise for at least 24 hours after the procedure.
Biological: GTU®-MultiHIV B Clade Vaccine
The investigational HIV-1 vaccine GTU®-MultiHIV B clade encodes for a MultiHIV antigen (synthetic fusion protein) built up by full-length polypeptides of Rev, Nef, Tat, p17 and p24 with more than 20 Th and CTL epitopes of protease, reverse transcriptase (RT) and gp160 regions of an HAN2 HIV-1 B clade isolate.
For use in prophylactic and replacement therapy, requiring the use of isotonic saline solution.
Grade 3 or above local solicited adverse event
Time frame: Two weeks after final vaccination
Grade 3 or above systemic clinical and laboratory solicited adverse event
Time frame: Four weeks after final vaccination
Any grade of adverse event that results in a clinical decision to discontinue further immunisations
Time frame: Four weeks after final vaccination
Immunogenicity
Change in IFN-γ ELISpot response to any of the pools of HIV-peptides encoded by the vaccine 2 weeks after the last immunisation relative to baseline, defined as a doubling in frequency from baseline or the presence of a response that was absent at baseline
Time frame: Two weeks after final vaccination
Any grade of adverse event that occurs in a participant that has received at least one immunisation
Time frame: Two weeks after final vaccination
Immunogenicity
Change in CD4+ and CD8+ T-cell cytokine responses (frequency and poly-functionality) to any of the pools of HIV peptides encoded by the vaccine, assessed by poly-chromatic ICS 2 weeks after the last immunisation
Time frame: Two weeks after final vaccination
Exploratory Immunogenicity
Change from baseline in epitope recognition (frequency and magnitude) as determined by ELISpot analysis using overlapping 15mer peptides
Time frame: Four weeks after final vaccination
Exploratory Immunogenicity
Change from baseline in the magnitude of antigen-specific IgG Ab response
Time frame: Four weeks after final vaccination
Exploratory Immunogenicity
Change from baseline in HIV proviral DNA within PBMC
Time frame: Four weeks after final vaccination
Exploratory Immunogenicity
Change from baseline in HIV plasma viral load (number of copies of HIV RNA per millilitre), measured by quantitative PCR
Time frame: Four weeks after final vaccination
Exploratory Immunogenicity
Change from baseline in the immune activation and surface expression markers on T cells from baseline measured by poly-chromatic flow cytometry
Time frame: Four weeks after final vaccination
Exploratory Immunogenicity
Change from baseline in CD4+ lymphocyte count
Time frame: Four weeks after final vaccination
This study is completed, as verified in Oct 2016. You cannot join it, but the record below documents what was studied.
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Imperial College London