search
Back to results

Safety And Immunogenicity Of Novel Candidate Blood-Stage Malaria Vaccine P27A : Phase Ia/Ib (P27A)

Primary Purpose

Malaria

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CH-Alum50
CH-GLA2.5/50
TZ Ver
TZ Alum 50
TZ GLA 2.5/10
TZ GLA5/50
TZ GLA2.5/50
Sponsored by
Centre Hospitalier Universitaire Vaudois
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Malaria focused on measuring plasmodium falciparum, long synthetic peptide, antibody, T cell, cytokine, vaccine, safety, phase 1

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Phase Ia Inclusion criteria:

    1. Healthy volunteers aged 18-45 years
    2. General good health based on history and clinical examination
    3. Written informed consent obtained before any study procedure
    4. Female volunteers practicing contraception before and up to 13 weeks after the last immunisation
    5. Available to participate in follow-up for the duration of study (34 weeks)
    6. Reachable by phone during the whole study period

  • Phase Ib inclusion criteria

    1. Healthy male volunteers aged 18-45 years
    2. General good health based on history and clinical examination
    3. Written informed consent obtained before any study procedure
    4. Available to participate in follow-up for the duration of study (34 weeks)
    5. Reachable by phone during the whole study period
    6. Having always lived in an area of low malaria transmission

Exclusion Criteria:

  • Phase Ia Exclusion criteria:

    1. Positive pregnancy test for females
    2. Actively breast feeding females
    3. Previous participation in any malaria vaccine trial
    4. Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the volunteers
    5. Any clinically significant laboratory abnormalities on screened blood samples beyond the normal range, as defined at the clinical trial site
    6. Enrolment in any other clinical trial during the whole trial period
    7. Intake of chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the 13 weeks preceding the screening visit or during the trial period except topical and inhaled steroids
    8. Volunteers unable to be closely followed for social, geographic or psychological reasons
    9. Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study
    10. Known hypersensitivity to any of the vaccine components (adjuvant or peptide)
    11. Vaccination or infusion of gammaglobulin from 4 weeks prior to the first vaccination and up to 6 weeks after the third vaccination
    12. Any history of malaria
    13. History of living in a malaria endemic area for more than five (5) years OR living in a malaria endemic area in early childhood. For practical purposes, all regions for which malaria chemoprophylaxis is advised by travel clinic are considered malaria endemic (cf. www.safetravel.ch).
    14. Known exposure to malaria in the previous six (6) months, defined as a visit to a malaria endemic region
    15. P27A ELISA positive OR parasite ELISA antibody positive AND Known exposure to malaria in a malaria endemic area
    16. P27A ELISA positive AND parasite ELISA antibody positive (with or without history of stay in a malaria endemic area)
    17. Intention to travel to malaria endemic countries during the study period
    18. Positive HIV, HBV or HCV tests

  • Phase Ib exclusion criteria

    1. Previously participated in any malaria vaccine trial
    2. Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the volunteers
    3. Any clinically significant laboratory abnormalities on screened blood samples beyond the normal range, as defined at the clinical trial site
    4. Enrolment in any other clinical trial during the whole trial period
    5. Intake of chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the thirteen weeks preceding the screening visit or during the trial period except topical and inhaled steroids
    6. Volunteers unable to be closely followed for social, geographic or psychological reasons
    7. Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study
    8. Known hypersensitivity to any of the vaccine components (adjuvant or peptide) or to any of the control vaccine components
    9. Vaccination OR infusion of gammaglobulins from four (4) weeks prior to the first vaccination and up to six (6) weeks after the third vaccination
    10. Previous vaccination with the control vaccine
    11. Positive HIV, HCV test or HBVsAg positive
    12. Malaria parasite positivity by microscopy and/or RDT
    13. Having had a history of confirmed malaria episode in the last five year

Sites / Locations

  • CHUV CRC
  • Bagamoyo Clinical Trial Unit (BCTU)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Alhydrogel CH-Alum50

CH-GLA2.5/50

Control rabies vaccine Verorub TM TZ Ver

Alhydrogel TZ Alum 50

GLA-SE TZ GLA 2.5/10

GLA-SE TZ GLA5/50

GLA-SE TZ GLA2.5/50

Arm Description

intramuscular administration to Swiss volunteers of Alhydrogel and P27A antigen (50 microg)

intramuscular administration to Swiss volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)

intramuscular administration of Rabies vaccine Verorub TM to in Phase IIb only to 8 Tanzanian volunteers in three injections

intramuscular administration to Tanzanian volunteers of Alhydrogel and P27A antigen (50 microg)

intramuscular administration to Tanzanian volunteers of GLA-SE (2.5 microg ) together with the P27A antigen (10 microg)

intramuscular administration to Tanzanian volunteers of GLA-SE (5 microg) together with the P27A antigen (50 microg)

intramuscular administration to Tanzanian volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)

Outcomes

Primary Outcome Measures

To evaluate the safety of P27A with Alhydrogel or GLA-SE as adjuvant, in healthy European adults not previously exposed to the parasite Plasmodium falciparum and in healthy African adults previously exposed to the parasite
The safety profile will be assessed on the basis of immediate local and systemic reactogenicity measured from Day 0 to Day 28 after each vaccination

Secondary Outcome Measures

Assessment of the humoral immune response to the vaccine antigen
The humoral response to the vaccine antigen will be assessed in all volunteers by ELISA to measure the level of total antigen specific IgG.
Assessment of the cellular immune response to the vaccine antigen
The cellular immune response will be assessed in all volunteers by measuring the T cell proliferation and cytokine production following in vitro stimulation with the vaccine antigen (by Luminex on cell culture supernatant after in vitro stimulation of PBMC for 6 days with the P27A peptide). Proliferation of carboxyfluorescein diacetate succinimidyl ester (CFSE) loaded CD3+ CD4+ and CD3+CD8+ T cells will be assayed by using polychromatic flow cytometry.

Full Information

First Posted
August 29, 2013
Last Updated
July 16, 2018
Sponsor
Centre Hospitalier Universitaire Vaudois
Collaborators
European Vaccine Initiative, European and Developing Countries Clinical Trials Partnership (EDCTP)
search

1. Study Identification

Unique Protocol Identification Number
NCT01949909
Brief Title
Safety And Immunogenicity Of Novel Candidate Blood-Stage Malaria Vaccine P27A : Phase Ia/Ib
Acronym
P27A
Official Title
Safety And Immunogenicity Of Novel Candidate Blood-Stage Malaria Vaccine P27A With Alhydrogel® Or GLA-SE As Adjuvant: A Staggered, Antigen And Adjuvant Dose-Finding, Randomized, Multi-Centre Phase Ia/Ib Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre Hospitalier Universitaire Vaudois
Collaborators
European Vaccine Initiative, European and Developing Countries Clinical Trials Partnership (EDCTP)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
P27A study is designed as a randomized phase Ia/Ib trial to evaluate the safety and immunogenicity of the blood stage candidate vaccine P27A against P. falciparum - P27A antigen and associated adjuvant (Alhydrogel or GLA-SE) - in malaria non exposed European volunteers(Switzerland; phase Ia) and malaria exposed African volunteers (Tanzania; phase Ib).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
plasmodium falciparum, long synthetic peptide, antibody, T cell, cytokine, vaccine, safety, phase 1

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alhydrogel CH-Alum50
Arm Type
Experimental
Arm Description
intramuscular administration to Swiss volunteers of Alhydrogel and P27A antigen (50 microg)
Arm Title
CH-GLA2.5/50
Arm Type
Experimental
Arm Description
intramuscular administration to Swiss volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)
Arm Title
Control rabies vaccine Verorub TM TZ Ver
Arm Type
Placebo Comparator
Arm Description
intramuscular administration of Rabies vaccine Verorub TM to in Phase IIb only to 8 Tanzanian volunteers in three injections
Arm Title
Alhydrogel TZ Alum 50
Arm Type
Experimental
Arm Description
intramuscular administration to Tanzanian volunteers of Alhydrogel and P27A antigen (50 microg)
Arm Title
GLA-SE TZ GLA 2.5/10
Arm Type
Experimental
Arm Description
intramuscular administration to Tanzanian volunteers of GLA-SE (2.5 microg ) together with the P27A antigen (10 microg)
Arm Title
GLA-SE TZ GLA5/50
Arm Type
Experimental
Arm Description
intramuscular administration to Tanzanian volunteers of GLA-SE (5 microg) together with the P27A antigen (50 microg)
Arm Title
GLA-SE TZ GLA2.5/50
Arm Type
Experimental
Arm Description
intramuscular administration to Tanzanian volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)
Intervention Type
Biological
Intervention Name(s)
CH-Alum50
Intervention Description
intramuscular administration to Swiss volunteers of Alhydrogel and P27A antigen (50 microg)
Intervention Type
Biological
Intervention Name(s)
CH-GLA2.5/50
Intervention Description
intramuscular administration to Swiss volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)
Intervention Type
Biological
Intervention Name(s)
TZ Ver
Intervention Description
intramuscular administration of Rabies vaccine Verorub TM to in Phase IIb only to 8 Tanzanian volunteers in three injections
Intervention Type
Biological
Intervention Name(s)
TZ Alum 50
Intervention Description
intramuscular administration to Tanzanian volunteers of Alhydrogel and P27A antigen (50 microg)
Intervention Type
Biological
Intervention Name(s)
TZ GLA 2.5/10
Intervention Description
intramuscular administration to Tanzanian volunteers of GLA-SE (2.5 microg ) together with the P27A antigen (10 microg)
Intervention Type
Biological
Intervention Name(s)
TZ GLA5/50
Intervention Description
intramuscular administration to Tanzanian volunteers of GLA-SE (5 microg) together with the P27A antigen (50 microg)
Intervention Type
Biological
Intervention Name(s)
TZ GLA2.5/50
Intervention Description
intramuscular administration to Tanzanian volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)
Primary Outcome Measure Information:
Title
To evaluate the safety of P27A with Alhydrogel or GLA-SE as adjuvant, in healthy European adults not previously exposed to the parasite Plasmodium falciparum and in healthy African adults previously exposed to the parasite
Description
The safety profile will be assessed on the basis of immediate local and systemic reactogenicity measured from Day 0 to Day 28 after each vaccination
Time Frame
15 months
Secondary Outcome Measure Information:
Title
Assessment of the humoral immune response to the vaccine antigen
Description
The humoral response to the vaccine antigen will be assessed in all volunteers by ELISA to measure the level of total antigen specific IgG.
Time Frame
15 months
Title
Assessment of the cellular immune response to the vaccine antigen
Description
The cellular immune response will be assessed in all volunteers by measuring the T cell proliferation and cytokine production following in vitro stimulation with the vaccine antigen (by Luminex on cell culture supernatant after in vitro stimulation of PBMC for 6 days with the P27A peptide). Proliferation of carboxyfluorescein diacetate succinimidyl ester (CFSE) loaded CD3+ CD4+ and CD3+CD8+ T cells will be assayed by using polychromatic flow cytometry.
Time Frame
15 months
Other Pre-specified Outcome Measures:
Title
Exploratory outcome measure: humoral response
Description
The humoral immune response quality will be assessed by measuring P27A specific antibodies IgG1, IgG2, IgG3, IgG4 subclasses by ELISA on samples obtained in all volunteers at day 0, week 8, week 12, week 26 and week 34.
Time Frame
15 months
Title
Exploratory outcome measure: cytokine production (ICS)
Description
The cellular immune response quality in all volunteers will be assessed by intracellular cytokine staining (ICS) for cytokines IL-2, TNF α, IFN γ and IL-10 in proliferating Carboxyfluorescein diacetate succinimidyl ester (CFSE) loaded CD3, CD4, and CD8 cells at day 0 and week 12 and 26.
Time Frame
15 months
Title
Exploratory outcome measure : antibody dependent cell cytotoxicity (ADCI)
Description
The functional humoral immune response will by ADCI in the GLA-SE and the Alhydrogel® group with the highest response, at day 0 and at an optimal time-point post vaccination.
Time Frame
15 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Phase Ia Inclusion criteria: Healthy volunteers aged 18-45 years General good health based on history and clinical examination Written informed consent obtained before any study procedure Female volunteers practicing contraception before and up to 13 weeks after the last immunisation Available to participate in follow-up for the duration of study (34 weeks) Reachable by phone during the whole study period Phase Ib inclusion criteria Healthy male volunteers aged 18-45 years General good health based on history and clinical examination Written informed consent obtained before any study procedure Available to participate in follow-up for the duration of study (34 weeks) Reachable by phone during the whole study period Having always lived in an area of low malaria transmission Exclusion Criteria: Phase Ia Exclusion criteria: Positive pregnancy test for females Actively breast feeding females Previous participation in any malaria vaccine trial Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the volunteers Any clinically significant laboratory abnormalities on screened blood samples beyond the normal range, as defined at the clinical trial site Enrolment in any other clinical trial during the whole trial period Intake of chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the 13 weeks preceding the screening visit or during the trial period except topical and inhaled steroids Volunteers unable to be closely followed for social, geographic or psychological reasons Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study Known hypersensitivity to any of the vaccine components (adjuvant or peptide) Vaccination or infusion of gammaglobulin from 4 weeks prior to the first vaccination and up to 6 weeks after the third vaccination Any history of malaria History of living in a malaria endemic area for more than five (5) years OR living in a malaria endemic area in early childhood. For practical purposes, all regions for which malaria chemoprophylaxis is advised by travel clinic are considered malaria endemic (cf. www.safetravel.ch). Known exposure to malaria in the previous six (6) months, defined as a visit to a malaria endemic region P27A ELISA positive OR parasite ELISA antibody positive AND Known exposure to malaria in a malaria endemic area P27A ELISA positive AND parasite ELISA antibody positive (with or without history of stay in a malaria endemic area) Intention to travel to malaria endemic countries during the study period Positive HIV, HBV or HCV tests Phase Ib exclusion criteria Previously participated in any malaria vaccine trial Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the volunteers Any clinically significant laboratory abnormalities on screened blood samples beyond the normal range, as defined at the clinical trial site Enrolment in any other clinical trial during the whole trial period Intake of chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the thirteen weeks preceding the screening visit or during the trial period except topical and inhaled steroids Volunteers unable to be closely followed for social, geographic or psychological reasons Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study Known hypersensitivity to any of the vaccine components (adjuvant or peptide) or to any of the control vaccine components Vaccination OR infusion of gammaglobulins from four (4) weeks prior to the first vaccination and up to six (6) weeks after the third vaccination Previous vaccination with the control vaccine Positive HIV, HCV test or HBVsAg positive Malaria parasite positivity by microscopy and/or RDT Having had a history of confirmed malaria episode in the last five year
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
François Spertini, MD
Organizational Affiliation
Centre Hospitalier Universitaire Vaudois (CHUV)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Salim Abdulla, MD
Organizational Affiliation
Bagamoyo Research and Training Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHUV CRC
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Facility Name
Bagamoyo Clinical Trial Unit (BCTU)
City
Bagamoyo
Country
Tanzania

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
29945169
Citation
Steiner-Monard V, Kamaka K, Karoui O, Roethlisberger S, Audran R, Daubenberger C, Fayet-Mello A, Erdmann-Voisin A, Felger I, Geiger K, Govender L, Houard S, Huber E, Mayor C, Mkindi C, Portevin D, Rusch S, Schmidlin S, Tiendrebeogo RW, Theisen M, Thierry AC, Vallotton L, Corradin G, Leroy O, Abdulla S, Shekalaghe S, Genton B, Spertini F, Jongo SA. The Candidate Blood-stage Malaria Vaccine P27A Induces a Robust Humoral Response in a Fast Track to the Field Phase 1 Trial in Exposed and Nonexposed Volunteers. Clin Infect Dis. 2019 Jan 18;68(3):466-474. doi: 10.1093/cid/ciy514.
Results Reference
derived
Links:
URL
http://www.euvaccine.eu
Description
European Vaccine Initiative

Learn more about this trial

Safety And Immunogenicity Of Novel Candidate Blood-Stage Malaria Vaccine P27A : Phase Ia/Ib

We'll reach out to this number within 24 hrs