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Optimising DNA Vaccinations in Healthy Volunteers (DNAVAC001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03663998
Recruitment Status : Completed
First Posted : September 10, 2018
Last Update Posted : September 12, 2018
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Imperial College London

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.

Condition or disease Intervention/treatment Phase
HIV-1-infection Biological: CN54ENV DNA Biological: GENEVAX® IL-12 DNA Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Masking Description: There will be no blinding
Primary Purpose: Prevention
Official Title: DNAVAC 001: A Phase 1 Open-labelled Trial to Optimise DNA Vaccination for Antibody Induction
Actual Study Start Date : August 15, 2015
Actual Primary Completion Date : May 10, 2017
Actual Study Completion Date : April 10, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: A
CN54ENV IM EP 400 g
Biological: CN54ENV DNA

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).


Active Comparator: B
CN54ENV IM EP 1000 g
Biological: CN54ENV DNA

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).


Active Comparator: C
CN54ENV IM EP 4000 g
Biological: CN54ENV DNA

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).


Active Comparator: D
CN54ENV ID EP 600 g
Biological: CN54ENV DNA

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).


Active Comparator: E
CN54ENV ID EP 1200 g
Biological: CN54ENV DNA

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).


Active Comparator: F
CN54ENV ID EP 1800 g
Biological: CN54ENV DNA

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).


Active Comparator: G

CN54ENV IM1 EP

+ pIL-12 (500 g)

Biological: GENEVAX® IL-12 DNA

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.


Active Comparator: H

CN54ENV IM1 EP

+ pIL-12 (1500 g)

Biological: GENEVAX® IL-12 DNA

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.


Active Comparator: I

CN54ENV IM1 EP

+ ID2 EP

Biological: CN54ENV DNA

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).





Primary Outcome Measures :
  1. Reactogenicity [ Time Frame: 12 Months ]
    Proportion of volunteers with moderate or greater reactogenicity (i.e., solicited adverse events) during a 7 day follow-up period after each vaccination.

  2. vaccine-related unsolicited adverse events [ Time Frame: 14 Months ]
    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.

  3. vaccine-related serious adverse events [ Time Frame: 16 Months ]
    Proportion of volunteers with vaccine-related serious adverse events (SAEs) throughout the study period.


Secondary Outcome Measures :
  1. Safety - event that occurred after vaccination [ Time Frame: 12 Months ]
    Any grade of adverse event that occurs in a participant that has received at least one immunisation by either method.

  2. Immunogenicity - kinetics of immune responses elicited by DNA vaccines [ Time Frame: 12 Months ]

    To assess the kinetics of immune responses elicited by each of the DNA regimens:

    • Frequency and titer of serum binding antibodies to HIV CN54 gp140 antigen by ELISA.


  3. Serum binding antibodies to HIV Env antigens [ Time Frame: 12 Months ]
    Frequency, titer and avidity of serum binding antibodies to other HIV Env antigens (alternative clades) by ELISA or other assays.

  4. Frequency and magnitude of HIV-gp140 specific B-cells [ Time Frame: 12 Months ]
    Frequency and magnitude of HIV-gp140 specific B-cell-mediated responses in the systemic compartment measured by B-cell ELISPOT.

  5. Mapping of serum binding antibodies [ Time Frame: 12 Months ]
    Mapping of serum binding antibodies using Env subunit constructs (e.g., V2 scaffolds and hotspots) by ELISA.

  6. Frequency and titer of serum neutralising antibodies [ Time Frame: 12 Months ]
    Frequency and titer of serum neutralising antibodies to homologous virus, and, if warranted a wider a panel of viruses representing different clades.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Men and women aged between 18 and 50 years on the day of screening
  2. BMI between 18-30
  3. Available for follow-up for the duration of the study
  4. Willing and able to give written informed consent
  5. 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
  6. Willing to undergo HIV testing
  7. Willing to undergo a genital infection screen, if indicated
  8. 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
  9. 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
  10. Agree to abstain from donating blood for three months after the end of their participation in the trial, or longer if necessary
  11. Registered with a GP for at least the past month
  12. Entered and clearance obtained from The Overvolunteering Prevention System (TOPS)

Exclusion Criteria:

  1. Pregnant or lactating
  2. Use of any medical topical treatment on the injection or application site within the last four weeks
  3. 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)
  4. History of syncope or fainting episodes within 1 year of study entry
  5. History of grand-mal epilepsy, seizure disorder or any history of prior seizure
  6. Individuals in which a skin-fold measurement (cutaneous and subcutaneous tissue) of the upper right or left thigh exceeds 40 mm
  7. Clinically relevant abnormality on history or examination
  8. Known hypersensitivity to any component of the vaccine formulations used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents
  9. 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
  10. Receipt of live attenuated vaccine within 30 days or other vaccine within 14 days of enrolment
  11. Receipt of an experimental vaccine containing HIV antigens at any time in the past
  12. Receipt of blood products or immunoglobin within 4 months of screening
  13. Participation in another trial of a medicinal product, completed less than 30 days prior to enrolment
  14. HIV 1 or 2 positive or indeterminate on screening
  15. Positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment
  16. Grade 1 or above routine laboratory parameters. Hyperbilirubinaemia to be considered an exclusion criterion only when confirmed to be conjugated bilirubinaemia
  17. Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators
  18. Presence of any surgical or traumatic metal implants at the sites of administration
  19. Unable to read and/or speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent
  20. Unlikely to comply with protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03663998


Sponsors and Collaborators
Imperial College London
Bill and Melinda Gates Foundation
Investigators
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Principal Investigator: Julie Fox, MD King's College London
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT03663998    
Other Study ID Numbers: 14SM2306
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Any publications based on the results of the Clinical Trial and originating from IC or the Investigators will be submitted for review to Ichor Medical Systems, Profectus Biosciences , UK HIV Vaccine Consortium (UK HVC) and Bill and Melinda Gates Foundation (BMGF), and will require their acceptance for further publications, according to the DNAVAC agreement
Supporting Materials: Clinical Study Report (CSR)
Time Frame: 18 Months from when the clinical trial officially closed
Access Criteria: Directly from the PI of the clinical trial

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
Antibody
Antibody-dependent cell-mediated cytotoxicity
Investigational Medicinal Product
neutralizing antibody responses