Clinical trial NCT01949909: Safety And Immunogenicity Of Novel Candidate Blood-Stage Malaria Vaccine P27A : Phase Ia/Ib
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Keywords: plasmodium falciparum
long synthetic peptide
antibody
T cell
cytokine
vaccine
safety
phase 1
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
Collaborators: name: European Vaccine Initiative
name: European and Developing Countries Clinical Trials Partnership (EDCTP)
First posted: 2013-09-25
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 15 months
Secondary outcomes:
measure: Assessment of the humoral immune response to the vaccine antigen
timeFrame: 15 months
measure: Assessment of the cellular immune response to the vaccine antigen
timeFrame: 15 months
Other outcomes:
measure: Exploratory outcome measure: humoral response
timeFrame: 15 months
measure: Exploratory outcome measure: cytokine production (ICS)
timeFrame: 15 months
measure: Exploratory outcome measure : antibody dependent cell cytotoxicity (ADCI)
timeFrame: 15 months
Locations:
city: Lausanne
country: Switzerland
facility: CHUV CRC
city: Bagamoyo
country: Tanzania
facility: Bagamoyo Clinical Trial Unit (BCTU)
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois (CHUV)
name: François Spertini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bagamoyo Research and Training Center
name: Salim Abdulla, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.