A Phase-I Study of a Nanoparticle-based Peptide Vaccine Against Dengue Virus

NCT04935801 | Completed Phase 1 DMC

• 1 other identifier: naNO-DENGUE
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Dengue

Keywords

Dengue; peptide vaccine; T-cell; nanoparticle; Dengue vaccine; T cell vaccine

Outcome Measures

Primary Outcomes (6)

• Safety: Solicited local & Systemic AEs

  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

  Through 14 days after prime or boost vaccination

• Safety: Unsolicited AEs

  Number of volunteers overall and in each dose group with unsolicited vaccine-associated adverse events (AEs) in each dose group

  Study Days 0-180 or through termination visit, if terminated early

• Safety: SAEs

  Number of volunteers overall and in each dose group with vaccine-associated serious adverse events (SAEs)

  Study Days 0-180 or through termination visit, if terminated early

• Safety: Adverse Events of Special Interest (AESI)

  Number of volunteers overall and in each dose group with vaccine-associated adverse events of special interest (AESIs)

  Study Days 0-180 or through termination visit, if terminated early

• Safety: Haemoglobin blood levels measurement

  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

  Screening, Days 7, 14, 28, 35

• Safety: Alkaline Phosphate Blood levels measurement

  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

  Screening, Days 7, 14, 28, 35

Secondary Outcomes (2)

• Immunogenicity: Proportion of participants with CD8-T cell specific to PepGNP-Dengue

  Study Days 0-180 or through termination visit, if terminated early

• Proportion of participants becoming seropositive (antibodies against Dengue virus)

  Study Days 0-180 or through termination visit, if terminated early

Study Arms (4)

LD Vehicle_GNP

SHAM COMPARATOR

Low dose (LD) comparator (2.5nmol) - gold nanoparticle (14.8ug) without peptides

Biological: LD vehicle-GNP

LD PepGNP-Dengue

EXPERIMENTAL

Low dose (LD) peptide vaccine (2.5nmol) - gold nanoparticle (14.8ug) plus peptides

Biological: LD PepGNP-Dengue

HD vehicle-GNP

SHAM COMPARATOR

High dose (HD) comparator (7.5nmol) - gold nanoparticle (44.5ug) without peptides

Biological: HD vehicle-GNP

HD PepGNP-Dengue

EXPERIMENTAL

High dose (HD) peptide vaccine (7.5nmol) - gold nanoparticle (44.5ug) plus peptides

Biological: HD PepGNP-Dengue

Interventions

LD vehicle-GNP BIOLOGICAL

Two intradermal injections in the upper arm spaced 21 days apart

LD Vehicle_GNP

LD PepGNP-Dengue BIOLOGICAL

Two intradermal injections in the upper arm spaced 21 days apart

LD PepGNP-Dengue

HD vehicle-GNP BIOLOGICAL

Two intradermal injections in the upper arm spaced 21 days apart

HD vehicle-GNP

HD PepGNP-Dengue BIOLOGICAL

Two intradermal injections in the upper arm spaced 21 days apart

HD PepGNP-Dengue

Eligibility Criteria

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

You may qualify if:

• Participant signed informed consent
• Residing in Switzerland

You may not qualify if:

• 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).

Sponsors & Collaborators

• Gylden Pharma Ltd: lead
• Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland: collaborator
• University of Lausanne Hospitals: collaborator

Study Sites (1)

Center for Primary Care and Public Health, (Unisante)

Lausanne, Canton of Vaud, 1004, Switzerland

Location

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• Blaise Genton, Prof

  Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: * 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 thus no shielding of the solution colour is needed.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 23, 2021
• Study Start: August 2, 2021
• Primary Completion: March 11, 2022
• Study Completion: September 15, 2022
• Last Updated: December 5, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Within 12 months of study completion
• Access Criteria: Peer-reviewed publication

Locations

CH (1)