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Evaluation of Safety and Immunogenicity of a T-Cell Priming Peptide Vaccine Against Dengue (naNO-DENGUE)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04935801
Recruitment Status : Recruiting
First Posted : June 23, 2021
Last Update Posted : June 23, 2021
Sponsor:
Collaborators:
Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland
University of Lausanne Hospitals
Information provided by (Responsible Party):
Emergex Vaccines Holding Ltd.

Brief Summary:

This trial aims to test the safety of 2 doses of a T-cell priming specific cocktail of Dengue viruses peptides representing all 4 DENV serotypes and mounted on a gold nanoparticle.

NOTE: This is the master protocol of a prospective 2-stage adaptive trial, which aims to add and test a Coronavirus vaccine candidate as well, in an identical trial design.


Condition or disease Intervention/treatment Phase
Dengue Biological: LD vehicle-GNP Biological: LD PepGNP-Dengue Biological: HD vehicle-GNP Biological: HD PepGNP-Dengue Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
  • This trial is double-blinded (blinded to investigators and participants)
  • Blinding will be maintained for the duration of the study
  • All allocations will remain coded to all volunteers and investigators. An independent pharmacy team at CHUV will label the Vaccine and Comparator doses with coded participant numbers but will not have access to the identifier list linking the code to the participant identity. All Vaccine and Comparator doses will be prepared and labelled away form investigators and stored in identical conditions.
  • The appearance of the comparators and doses will be identical. The solutions of both are indistinguishable within the dosage group and this no shielding of the solution colour is needed.
Primary Purpose: Prevention
Official Title: naNO-DENGUE: A Phase I Double-blind, Randomised, Vehicle-controlled, Dose-finding, Safety Study of a Synthetic Nanoparticle-based T-Cell Priming Peptide Vaccine Against Dengue Virus in Healthy Adults in Switzerland
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dengue

Arm Intervention/treatment
Sham Comparator: LD Vehicle_GNP
Low dose (LD) comparator (2.5nmol) - gold nanoparticle (14.8ug) without peptides
Biological: LD vehicle-GNP
Two intradermal injections in the upper arm spaced 21 days apart

Experimental: LD PepGNP-Dengue
Low dose (LD) peptide vaccine (2.5nmol) - gold nanoparticle (14.8ug) plus peptides
Biological: LD PepGNP-Dengue
Two intradermal injections in the upper arm spaced 21 days apart

Sham Comparator: HD vehicle-GNP
High dose (HD) comparator (7.5nmol) - gold nanoparticle (44.5ug) without peptides
Biological: HD vehicle-GNP
Two intradermal injections in the upper arm spaced 21 days apart

Experimental: HD PepGNP-Dengue
High dose (HD) peptide vaccine (7.5nmol) - gold nanoparticle (44.5ug) plus peptides
Biological: HD PepGNP-Dengue
Two intradermal injections in the upper arm spaced 21 days apart




Primary Outcome Measures :
  1. Safety: Solicited local and systemic AEs [ Time Frame: Through 14 days after prime or boost vaccination ]
    Number of volunteers overall and in each dose group with local or systemic vaccine reactogenicity, based on evaluation of solicited adverse events (AEs) recorded on subject memory aids or during clinical assessments

  2. Safety: Unsolicited AEs [ Time Frame: Study Days 0-180 or through termination visit, if terminated early ]
    Number of volunteers overall and in each dose group with unsolicited vaccine-associated adverse events (AEs) in each dose group

  3. Safety: SAEs [ Time Frame: Study Days 0-180 or through termination visit, if terminated early ]
    Number of volunteers overall and in each dose group with vaccine-associated serious adverse events (SAEs)

  4. Safety: Adverse Events of Special Interest (AESI) [ Time Frame: Study Days 0-180 or through termination visit, if terminated early ]
    Number of volunteers overall and in each dose group with vaccine-associated adverse events of special interest (AESIs)

  5. Safety: Haemoglobin blood levels measurement [ Time Frame: Days 0 (pre-prime dose), 7, 14, 21 (pre-booster dose), 28, 35, 90 and 180 ]

    Number of volunteers overall and in each dose group with abnormal results in blood test regarding haemoglobin (Hb) measured in g/l.

    Reference range (from "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" - https://www.fda.gov/media/73679/download):

    Female 117-157 g/l / Male: 133-177 g/l)

    Anaemia reported as:

    GRADE 1: <117 - 100 g/l GRADE 2: <100 - 80 g/l GRADE 3: < 80 g/l


  6. Safety: Alkaline phosphate blood levels measurement [ Time Frame: Days 0 (pre-prime dose), 7, 14, 21 (pre-booster dose), 28, 35, 90 and 180 ]

    Number of volunteers overall and in each dose group with abnormal results in blood test regarding Alkaline phosphate measured in U/L.

    Reference ranges (from "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" - https://www.fda.gov/media/73679/download): 36-120 U/L

    Elevation in Alkaline phosphate reported as:

    GRADE 1: 121 - 300 U/L GRADE 2: >300 - 600 U/L GRADE 3: >600 U/L



Secondary Outcome Measures :
  1. Immunogenicity: Proportion of participants with CD8-T cell specific to PepGNP-Dengue [ Time Frame: Study Days 0-180 or through termination visit, if terminated early ]

    Specific CD8 T cell responses: Assessment of memory CD8 T cell response performed by primarily measuring: CCR7lo / CD62Llo / CD27- / CD45RA-

    Assessment of T and B cell responses: CD8 Activation-Induced Markers (AIM) CD8+/CD69+/CD137+ and CD8+/CD107a+

    Activation markers: The induction of cell activation by ex vivo quantification of activation markers on various cell subsets by flow cytometry.


  2. Proportion of participants becoming seropositive (antibodies against Dengue virus) [ Time Frame: Study Days 0-180 or through termination visit, if terminated early ]

    Dengue serology rapid test: Serology to detect antibodies against the four dengue serotypes by rapid test

    Anti-DENV2 Ig: Serology to detect antibodies against natural DENV (lysate or inactivated viral particles), by ELISA




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 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged 18 to 45 years on the day of inclusion
  • Participant signed informed consent
  • Residing in Switzerland

Exclusion Criteria:

  • Participant is pregnant, lactating, or of childbearing potential
  • Participation in the 4 weeks preceding the first trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
  • Receipt of any vaccine in the 4 weeks preceding the first trial vaccination (excepting influenza vaccination, which may be received up to 2 weeks before first study vaccine) or planned receipt of any vaccine in the 4 weeks following each trial vaccination.
  • Previous vaccination against Japanese encephalitis (JE), Yellow Fever (YF), or any dengue virus vaccine (monovalent or tetravalent) at any time in the past with either a trial vaccine or another vaccine (commercial or investigational) based on medical history
  • Self-reported or documented history of flavivirus (FV) infection (e.g. DENV, YF, WNV, JE, TBE), confirmed either clinically or serologically
  • Receipt of immunoglobulins, blood or blood-derived products in the past 3 months
  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy
  • Self-reported or documented seropositivity for human immunodeficiency virus (HIV), hepatitis B natural infection (HBcAb positive serology), or hepatitis C
  • Previous residence for more than 12 months in, or travel in the last 30 days to FV-endemic regions (excluding TBE and WNV)
  • At high risk for dengue infection during the trial
  • Known systemic hypersensitivity to any of the vaccine components (e.g. gold), or history of a life-threatening reaction to vaccines, or to a vaccine containing any of the same substances
  • Current alcohol abuse or drug addiction (reported or suspected)
  • Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
  • Thrombocytopenia or any coagulation disorder
  • Identified as an Investigator or employee of the Investigator or study centre with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study (i.e. in the employment of the Tropivac clinic or DFRI unit at Unisanté).
  • Refusal to be informed in the event that relevant results concerning the participant's health are revealed.

The following events constitute contraindications to the administration of the investigational product on the day of planned vaccination.

The participant must be followed until resolution of the event as with any medical event and may be considered for vaccination at a later date (maximum 14 days later) or withdrawn at the discretion of the Investigator. Delays due to these events do not constitute a protocol deviation.

  • Temperature of >37.5°C at the time of vaccination
  • Acute disease at the time of vaccination
  • If there is a clinical/epidemiological suspicion of COVID-19 (according to the clinician's judgement), the participant will be asked to first take a PCR/rapid test for SARS-CoV2, and the vaccination will be delayed until the result comes back negative and the symptoms have resolved.

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): NCT04935801


Contacts
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Contact: Blaise Genton, Prof +41785565868 blaise.genton@unisante.ch
Contact: Alix Miauton, MD +41797696551 alix.miauton@unisante.ch

Locations
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Switzerland
Center for Primary Care and Public Health, (Unisante) Recruiting
Lausanne, Vaud, Switzerland, 1004
Contact: Blaise Genton, Prof    +41785565868    blaise.genton@unisante.ch   
Contact: Alix Miauton, MD    +41797696551    alix.miauton@unisante.ch   
Sponsors and Collaborators
Emergex Vaccines Holding Ltd.
Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland
University of Lausanne Hospitals
Investigators
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Principal Investigator: Blaise Genton, Prof Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland
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Responsible Party: Emergex Vaccines Holding Ltd.
ClinicalTrials.gov Identifier: NCT04935801    
Other Study ID Numbers: naNO-DENGUE
First Posted: June 23, 2021    Key Record Dates
Last Update Posted: June 23, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

The Investigators will be involved in writing and/or reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study.

Apart from obvious flaws to the conduct of the study, which may preclude data publication, safety and efficacy data will be published under the supervision and authorization of PI and Sponsor.

Publication will include as much individual level data as possible to ensure reproducibility of results without compromising participant privacy.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Within 12 months of study completion
Access Criteria: Peer-reviewed publication

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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 Emergex Vaccines Holding Ltd.:
Dengue
peptide vaccine
T-cell
nanoparticle
Dengue vaccine
T cell vaccine
Additional relevant MeSH terms:
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Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral