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

July 16, 2018 updated by: François Spertini, Centre Hospitalier Universitaire Vaudois

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Lausanne, Switzerland, 1011
        • CHUV CRC
  • Tanzania
      • Bagamoyo, Tanzania
        • Bagamoyo Clinical Trial Unit (BCTU)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Alhydrogel CH-Alum50
intramuscular administration to Swiss volunteers of Alhydrogel and P27A antigen (50 microg)
Biological: CH-Alum50
intramuscular administration to Swiss volunteers of Alhydrogel and P27A antigen (50 microg)
Experimental: CH-GLA2.5/50
intramuscular administration to Swiss volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)
Biological: CH-GLA2.5/50
intramuscular administration to Swiss volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)
Placebo Comparator: Control rabies vaccine Verorub TM TZ Ver
intramuscular administration of Rabies vaccine Verorub TM to in Phase IIb only to 8 Tanzanian volunteers in three injections
Biological: TZ Ver
intramuscular administration of Rabies vaccine Verorub TM to in Phase IIb only to 8 Tanzanian volunteers in three injections
Experimental: Alhydrogel TZ Alum 50
intramuscular administration to Tanzanian volunteers of Alhydrogel and P27A antigen (50 microg)
Biological: TZ Alum 50
intramuscular administration to Tanzanian volunteers of Alhydrogel and P27A antigen (50 microg)
Experimental: GLA-SE TZ GLA 2.5/10
intramuscular administration to Tanzanian volunteers of GLA-SE (2.5 microg ) together with the P27A antigen (10 microg)
Biological: TZ GLA 2.5/10
intramuscular administration to Tanzanian volunteers of GLA-SE (2.5 microg ) together with the P27A antigen (10 microg)
Experimental: GLA-SE TZ GLA5/50
intramuscular administration to Tanzanian volunteers of GLA-SE (5 microg) together with the P27A antigen (50 microg)
Biological: TZ GLA5/50
intramuscular administration to Tanzanian volunteers of GLA-SE (5 microg) together with the P27A antigen (50 microg)
Experimental: GLA-SE TZ GLA2.5/50
intramuscular administration to Tanzanian volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)
Biological: TZ GLA2.5/50
intramuscular administration to Tanzanian volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: 15 months
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
15 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assessment of the humoral immune response to the vaccine antigen
Time Frame: 15 months
The humoral response to the vaccine antigen will be assessed in all volunteers by ELISA to measure the level of total antigen specific IgG.
15 months
Assessment of the cellular immune response to the vaccine antigen
Time Frame: 15 months
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.
15 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Exploratory outcome measure: humoral response
Time Frame: 15 months
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.
15 months
Exploratory outcome measure: cytokine production (ICS)
Time Frame: 15 months
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.
15 months
Exploratory outcome measure : antibody dependent cell cytotoxicity (ADCI)
Time Frame: 15 months
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.
15 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre Hospitalier Universitaire Vaudois

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
European and Developing Countries Clinical Trials Partnership (EDCTP)
European Vaccine Initiative

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Francois Spertini, MD, Centre Hospitalier Universitaire Vaudois (CHUV)
  • Principal Investigator: Salim Abdulla, MD, Bagamoyo Research and Training Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 29, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 18, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P27A_1_13

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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