Immunogenicity of Three HIV GTU® MultiHIV DNA Immunisations Administered Via Intramuscular, Intradermal and Transcutaneous Routes

NCT02075983 | Unknown Phase 1 DMC

• 2 other identifiers: CRO20492011-003171-11
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Our research is part of the global effort to develop a vaccine against HIV. We aim to develop a non-invasive, needle-free 'transcutaneous' vaccine. It will be a water-based solution which is placed on the surface of the skin of the upper arm, after the hairs have been stripped away. The active component of the vaccine - DNA which contains genes derived from the virus - will enter through the hair follicles from which the hair has been stripped. The DNA will get into cells, which will use the HIV genes to make copies of virus proteins. These proteins will stimulate the body's immune system and, we hope, make it able to protect against HIV infection. The research is to assess the safety of this approach, and how good it is at stimulating the immune system. We will combine the 'transcutaneous' vaccine with an 'intramuscular' version which is injected into the muscle of the thigh, and compare this combination with: intramuscular plus 'intradermal' (injection into the skin); and intramuscular with added 'electroporation' - use of a pulse of electricity to increase uptake of DNA vaccines. We will invite healthy men and women to take part in this research. Volunteers will first be assessed to ensure they are eligible to participate. A total of 30 will be enrolled and each will receive three vaccinations over the course of 12 weeks. We will assess the effects of the vaccinations by recording any symptoms experienced by the volunteers, and by analysing samples of their blood. The research will take place at the St Mary's Hospital campus of Imperial College London, UK. The DNA component of the vaccine is an experimental substance, so we will monitor very closely the wellbeing of the men and women who participate in the research.

Conditions

HIV

Keywords

HIV; Vaccine; Immunisation; DNA; Adverse events; Electroporation; Transcutaneous; GTU MultiHIV B Clade; Antibody; Intramuscular; Immunogenicity

Outcome Measures

Primary Outcomes (2)

• Immunogenicity Immunogenicity

  The primary immunogenicity endpoint is the presence of a T cell response measured by IFN-γ ELISPOT assay using frozen PBMCs collected 2 weeks after the final vaccination.

  2 weeks after the final vaccination

• Safety

  Primary safety endpoint is the presence of a grade 3 or above local or systemic solicited adverse event or any adverse event that results in a clinical decision to discontinue further immunisations.

  Four weeks after final immunisation

Secondary Outcomes (2)

• Immunogenicity

  Four weeks after final immunisation

• Safety

  Four weeks after final immunisation

Other Outcomes (1)

• Exploratory immunogenicity endpoint

  Four weeks after final immunisation

Study Arms (3)

Group 3 (IM+EP)

EXPERIMENTAL

Group 3 will receive 12.0mg of vaccine over 12 weeks administered with EP using the Trigid Ichor device. We expect to see the greatest proportion of individuals making T cell and antigen specific antibody responses responses in this group. Depending on the magnitude of the effects, the differences between group 3 and the other groups may be statistically significant.

Biological: GTU®-multiHIV B clade

Group 2 (IM+TC)

EXPERIMENTAL

Group 2 will also receive 13.2mg of vaccine over 12 weeks, with 12.0mg given IM and 1.2mg TC. We are interested in the impact of TC relative to ID vaccination on the ratio between HIV-specific T-cell responses, and whether or not CD8+ Tcells are favoured by this route.

Biological: GTU®-multiHIV B clade

Group 1 (IM+ID)

ACTIVE COMPARATOR

Group 1 will serve as the "reference" arm and this group will receive a total dose of 13.2mg vaccine over 12 weeks with 12.0mg given IM and 1.2mg ID. This is 7.2mg more than has been given previously to healthy individuals and 6.2 mg more than given to those HIV-infected but similar doses of HIV DNA vaccines have been given in other trials with no serious consequences.

Biological: GTU®-multiHIV B clade

Interventions

GTU®-multiHIV B clade BIOLOGICAL

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 the HAN2 HIV-1 B clade.

Also known as: 4.0mg GTU®-multiHIV B clade

Group 1 (IM+ID); Group 2 (IM+TC); Group 3 (IM+EP)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women aged between 18 and 45 years on the day of screening
• BMI between 19-28
• Available for follow-up for the duration of the study (\~6 months from screening)
• Willing and able to give written informed consent
• At low risk of HIV and willing to remain so for the duration of the study defined as:
• no history of injecting drug use in the previous ten years
• no gonorrhoea or syphilis in the last six months
• no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months
• no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative
• no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner
• Willing to undergo a HIV test
• Willing to undergo a genital infection screen
• If heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable or implanted contraceptive; consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first vaccination until 4 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination
• If heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination
• Agree to abstain from donating blood for three months after the end of their participation in the trial, or longer if necessary

You may not qualify if:

• Pregnant or lactating
• Use of any topical treatment on the injection or application site within the last four weeks
• No UV tanning sessions or strong sun exposure within four weeks prior to the study and a willingness to avoid these during the study period.
• Excessive terminal hair growth on the investigational skin areas (to be assessed by reference to a photograph which will be available during screening visit.
• Individuals in which a skin-fold measurement (cutaneous and subcutaneous tissue) of the upper right or left thigh exceeds 40 mm.
• Clinically relevant abnormality on history or examination including
• history of grand-mal epilepsy, seizure disorder or any history of prior seizure
• history of syncope or fainting episodes within 1 year of study entry.
• severe eczema
• liver disease with inadequate hepatic function
• any skin condition which may interfere with the trial assessment on the injection site
• haematological, metabolic, gastrointestinal or cardio-pulmonary disorders including an abnormal ECG.
• uncontrolled infection; toxic shock syndrome
• autoimmune disease, immunodeficiency or use of immunosuppressives in preceding 3 months
• Known hypersensitivity to any component of the vaccine formulations used in this trial, or a seafood allergy or have severe or multiple allergies to drugs or pharmaceutical agents

Sponsors & Collaborators

• Imperial College London: lead
• CUT'HIVAC Cutaneous HIV Vaccination: collaborator

Study Sites (1)

Imperial College London

Greater London, W2 1PG, United Kingdom

RECRUITING

Study Officials

• Sheena McCormack, MSc, FRCP

  Senior Clinical Scientist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aleisha N Miller, PhD

CONTACT

0207-594-1319; aleisha.miller1@imperial.ac.uk

Mary Cross, PhD

CONTACT

020 7594 2649; m.cross@imperial.ac.uk

Study Design

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

Study Record Dates

• First Submitted: February 27, 2014
• First Posted: March 3, 2014
• Study Start: June 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: December 1, 2015
• Last Updated: March 3, 2014

Record last verified: 2013-04

Locations

GB (1)