Optimising DNA Vaccinations in Healthy Volunteers

NCT03663998 | Completed Phase 1

• 1 other identifier: 14SM2306
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a two part study to evaluate the immunogenicity and tolerability of DNA-C CN54ENV plasmid DNA (CN54ENV) administered with electroporation (EP), with and without DNA encoding recombinant interleukin-12 (GENEVAX® IL-12). Part 1 is exploratory and designed to select conditions capable of promoting enhanced B cell responses in a limited number of volunteers. Part 2 is dependent upon Part 1 and is designed to study the fine specificity of the B-cell immune responses to CN54ENV DNA in an expanded number of subjects. Data from both stages will be combined for safety and immunological analysis.

Conditions

HIV-1-infection

Keywords

Antibody; Antibody-dependent cell-mediated cytotoxicity; Investigational Medicinal Product; neutralizing antibody responses

Outcome Measures

Primary Outcomes (3)

• Reactogenicity

  Proportion of volunteers with moderate or greater reactogenicity (i.e., solicited adverse events) during a 7 day follow-up period after each vaccination.

  12 Months

• vaccine-related unsolicited adverse events

  Proportion of volunteers with moderate or greater and/or vaccine-related unsolicited adverse events (AEs), including safety laboratory (biochemical, haematological) parameters, up to 28 days post each vaccination.

  14 Months

• vaccine-related serious adverse events

  Proportion of volunteers with vaccine-related serious adverse events (SAEs) throughout the study period.

  16 Months

Secondary Outcomes (6)

• Safety - event that occurred after vaccination

  12 Months

• Immunogenicity - kinetics of immune responses elicited by DNA vaccines

  12 Months

• Serum binding antibodies to HIV Env antigens

  12 Months

• Frequency and magnitude of HIV-gp140 specific B-cells

  12 Months

• Mapping of serum binding antibodies

  12 Months

Study Arms (9)

A

ACTIVE COMPARATOR

CN54ENV IM EP 400 g

Biological: CN54ENV DNA

B

ACTIVE COMPARATOR

CN54ENV IM EP 1000 g

Biological: CN54ENV DNA

C

ACTIVE COMPARATOR

CN54ENV IM EP 4000 g

Biological: CN54ENV DNA

D

ACTIVE COMPARATOR

CN54ENV ID EP 600 g

Biological: CN54ENV DNA

E

ACTIVE COMPARATOR

CN54ENV ID EP 1200 g

Biological: CN54ENV DNA

F

ACTIVE COMPARATOR

CN54ENV ID EP 1800 g

Biological: CN54ENV DNA

G

ACTIVE COMPARATOR

CN54ENV IM1 EP \+ pIL-12 (500 g)

Biological: GENEVAX® IL-12 DNA

H

ACTIVE COMPARATOR

CN54ENV IM1 EP \+ pIL-12 (1500 g)

Biological: GENEVAX® IL-12 DNA

I

ACTIVE COMPARATOR

CN54ENV IM1 EP \+ ID2 EP

Biological: CN54ENV DNA

Interventions

CN54ENV DNA BIOLOGICAL

CN54ENV DNA concentration 4 ± 0.7 mg/mL is formulated in 1 x PBS All administrations of CN54ENV will be by in vivo electroporation using the Ichor Medical Systems TriGrid Delivery System for intramuscular (TDS-IM) or intradermal use (TDS-ID) and will be delivered into the upper thigh(s).

A; B; C; D; E; F; I

GENEVAX® IL-12 DNA BIOLOGICAL

GENEVAX® IL-12 DNA, concentration 2 mg/mL with a fill volume of 1.0 mL (1.0 ± 0.1mL), is formulated in 30 mM citrate buffer. GENEVAX® IL-12 DNA is mixed with the CN54ENV DNA immediately prior to administration.

G; H

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women aged between 18 and 50 years on the day of screening
• BMI between 18-30
• Available for follow-up for the duration of the study
• Willing and able to give written informed consent
• At low risk of HIV infection 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 or vaginal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative
• Willing to undergo HIV testing
• Willing to undergo a genital infection screen, if indicated
• If heterosexually active female, using an effective method of contraception with partner: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); bilateral tubual occlusion, vasectomised partner (if sole partner); sexual abstinence (based on historical preferred and usual lifestyle), from 30 days prior to the first vaccination until 30 days after the last, and willing to undergo urine pregnancy tests prior to each vaccination
• If heterosexually active male, using male contraception (condom) with their partner from the first day of vaccination until 4 months after the last vaccination. Furthermore additional use of an effective method of contraception (as listed above) should be recommended for any non-pregnant female partner over the same period
• Agree to abstain from donating blood for three months after the end of their participation in the trial, or longer if necessary
• Registered with a GP for at least the past month

You may not qualify if:

• Pregnant or lactating
• Use of any medical topical treatment on the injection or application site within the last four weeks
• History of cardiac arrhythmia or palpitations (e.g, supraventricular tachycardia, atrial fibrillation, frequent ectopy), or sinus bradycardia prior to study entry (sinus arrhythmia is not excluded)
• History of syncope or fainting episodes within 1 year of study entry
• History of grand-mal epilepsy, seizure disorder or any history of prior seizure
• 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
• 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
• local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours
• general: fever ≥39.5°C within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
• Receipt of live attenuated vaccine within 30 days or other vaccine within 14 days of enrolment
• Receipt of an experimental vaccine containing HIV antigens at any time in the past
• Receipt of blood products or immunoglobin within 4 months of screening
• Participation in another trial of a medicinal product, completed less than 30 days prior to enrolment

Sponsors & Collaborators

• Imperial College London: lead
• Bill and Melinda Gates Foundation: collaborator

Study Officials

• Julie Fox, MD

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: There will be no blinding
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Groups A-F will be recruited sequentially, groups G and H once the optimal dose for IM has been determined, and group I selecting the optimal doses for IM and ID form groups A-F for combined administration. This will represent a divided dose group across two different anatomical sites. Each group will receive four vaccinations (at 0, 4, 8 and 12 weeks). The choice of four vaccinations is based on the observation that antibody responses to DNA vaccination in mice plateau after the fourth vaccination, while in rabbits after the third. Hence it is unclear where they may plateau in humans.

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: September 10, 2018
• Study Start: August 15, 2015
• Primary Completion: May 10, 2017
• Study Completion: April 10, 2018
• Last Updated: January 27, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: 18 Months from when the clinical trial officially closed
• Access Criteria: Directly from the PI of the clinical trial