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

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: NCT01949909
Recruitment Status : Completed
First Posted : September 25, 2013
Last Update Posted : July 18, 2018
Sponsor:
Collaborators:
European Vaccine Initiative (EVI), Heidelberg, Germany
European & Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
François Spertini, Centre Hospitalier Universitaire Vaudois

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).

Condition or disease Intervention/treatment Phase
Malaria Biological: CH-Alum50 Biological: CH-GLA2.5/50 Biological: TZ Ver Biological: TZ Alum 50 Biological: TZ GLA 2.5/10 Biological: TZ GLA5/50 Biological: TZ GLA2.5/50 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
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 Start Date : March 2014
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
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)




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.



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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:

  • 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

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): NCT01949909


Locations
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Switzerland
CHUV CRC
Lausanne, Switzerland, 1011
Tanzania
Bagamoyo Clinical Trial Unit (BCTU)
Bagamoyo, Tanzania
Sponsors and Collaborators
Centre Hospitalier Universitaire Vaudois
European Vaccine Initiative (EVI), Heidelberg, Germany
European & Developing Countries Clinical Trials Partnership (EDCTP)
Investigators
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Principal Investigator: François Spertini, MD Centre Hospitalier Universitaire Vaudois (CHUV)
Principal Investigator: Salim Abdulla, MD Bagamoyo Research and Training Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: François Spertini, Dr, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT01949909    
Other Study ID Numbers: P27A_1_13
First Posted: September 25, 2013    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Keywords provided by François Spertini, Centre Hospitalier Universitaire Vaudois:
plasmodium falciparum
long synthetic peptide
antibody
T cell
cytokine
vaccine
safety
phase 1
Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Aluminum Hydroxide
Vaccines
Aluminum sulfate
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antacids
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents