The Safety and Immunogenicity of the DNA-GTU Vaccine Administered to HIV-infected Patients on ART vs Placebo

NCT02457689 | Completed Phase 1 DMC

• 1 other identifier: 14SM2037
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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):

• Transcutaneous (TC) delivery to enhance intramuscular delivery and
• 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.

Conditions

HIV

Keywords

Human Immunodeficiency Virus; Immunodeficiency Virus, Human

Outcome Measures

Primary Outcomes (4)

• Grade 3 or above local solicited adverse event

  Two weeks after final vaccination

• Grade 3 or above systemic clinical and laboratory solicited adverse event

  Four weeks after final vaccination

• Any grade of adverse event that results in a clinical decision to discontinue further immunisations

  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

  Two weeks after final vaccination

Secondary Outcomes (2)

• Any grade of adverse event that occurs in a participant that has received at least one immunisation

  Two weeks after final vaccination

• Immunogenicity

  Two weeks after final vaccination

Other Outcomes (6)

• Exploratory Immunogenicity

  Four weeks after final vaccination

• Exploratory Immunogenicity

  Four weeks after final vaccination

• Exploratory Immunogenicity

  Four weeks after final vaccination

Study Arms (4)

Group 1 (Transcutaneous and Placebo)

PLACEBO COMPARATOR

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)

ACTIVE COMPARATOR

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)

PLACEBO COMPARATOR

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)

ACTIVE COMPARATOR

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

Interventions

GTU®-MultiHIV B Clade Vaccine 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 an HAN2 HIV-1 B clade isolate.

Group 2 (Transcutaneous and Active); Group 4 (Electroporation and Active)

Sodium chloride BP OTHER

For use in prophylactic and replacement therapy, requiring the use of isotonic saline solution.

Group 1 (Transcutaneous and Placebo); Group 3 (Electroporation and Placebo)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female
• Aged between 18 and 45 years on the day of screening
• BMI between 19-30
• Available for follow-up for the duration of the study
• Willing and able to give written informed consent
• HIV-1 Clade B infection documented by confirmed antibody test
• Confirmed on 2 separate occasions in the 6 month period prior to enrolment to have viral load \< 200 copies HIV RNA/ml whilst on ART
• Nadir CD4+ \> 250 CD4 lymphocytes AND screening CD4 \>200 CD4 lymphocytes
• Willing to avoid UV tanning or strong sun exposure during the immunisation period of the study
• Willing to avoid all other vaccines within four weeks of scheduled study vaccinations
• 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

You may not qualify if:

• Pregnant or lactating
• Use of regular topical treatment on the injection or application site within the last four weeks
• UV tanning sessions or strong sun exposure within four weeks prior to enrolment
• 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
• liver disease including active hepatitis B (surface antigen positive) or C (PCR positive)
• any skin condition which may interfere with the trial assessment of the injection site
• haematological, metabolic, gastrointestinal (excluding gastritis) or cardio-pulmonary disorders (excluding mild asthma)
• a clinically significant abnormality on the ECG
• autoimmune disease, or use of regular, systemic immunosuppressives in preceding 3 months
• Known hypersensitivity to any component of the vaccine formulations used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents
• History of severe local or general reaction to vaccination defined as

Sponsors & Collaborators

• Imperial College London: lead
• European Commission: collaborator

Study Sites (1)

Imperial College London

Greater London, W2 1PG, United Kingdom

Location

Related Publications (1)

• Haidari G, Day S, Wood M, Ridgers H, Cope AV, Fleck S, Yan C, Reijonen K, Hannaman D, Spentzou A, Hayes P, Vogt A, Combadiere B, Cook A, McCormack S, Shattock RJ. The Safety and Immunogenicity of GTU(R)MultiHIV DNA Vaccine Delivered by Transcutaneous and Intramuscular Injection With or Without Electroporation in HIV-1 Positive Subjects on Suppressive ART. Front Immunol. 2019 Dec 13;10:2911. doi: 10.3389/fimmu.2019.02911. eCollection 2019.

  PMID: 31921170 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Sheena McCormack, Phd, MD

  Medical Research Council University College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: May 29, 2015
• Study Start: July 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: November 10, 2016

Record last verified: 2016-10

Locations

GB (1)