Safety and Immunogenicity of Recombinant Pichia Pastoris AMA1-DiCo Candidate Malaria Vaccine With GLA-SE and Alhydrogel ® as Adjuvant in Healthy Malaria Non-Exposed European and Malaria Exposed African Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Institut National de la Santé Et de la Recherche Médicale, France
Sponsor:
Collaborators:
EVI
BPRC
CIC COCHIN
CNRFP
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier:
NCT02014727
First received: December 12, 2013
Last updated: July 25, 2014
Last verified: January 2014
  Purpose

The primary objective is to evaluate the safety of 3 doses given at D0, W4, and W26 of 50 µg dosage of AMA1-DiCo adjuvanted either with GLA-SE or Alhydrogel® in healthy European adults not previously exposed to the parasite P.falciparum and in healthy African adults exposed to the parasite. The safety and the tolerability of the vaccine will be assessed on the rate of solicited and unsolicited events/reactions. The safety profile will include local and systemic reactions/events as well as the biological safety, based on a clinically significant change of the baseline value of the main biological criteria.


Condition Intervention Phase
Safety of Candidate Malaria Vaccine
Biological: Group A1 : 50µg AMA1-DiCo + Alhydrogel
Biological: Group A2 : 50 µg AMA1-DiCo+ GLA-SE
Biological: Group B2 : Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Safety and Immunogenicity of Recombinant Pichia Pastoris AMA1-DiCo Candidate Malaria Vaccine With GLA-SE and Alhydrogel ® as Adjuvant in Healthy Malaria Non-Exposed European and Malaria Exposed African Adults:a Staggered Phase Ia/Ib, Randomised, Double-blind, Multi-Centre Trial

Resource links provided by NLM:


Further study details as provided by Institut National de la Santé Et de la Recherche Médicale, France:

Primary Outcome Measures:
  • Number of Adverse events [ Time Frame: Up to four weeks after the third vaccination. ] [ Designated as safety issue: Yes ]

    The safety profile will be assessed in all volunteers on the following criteria:

    • Immediate reactogenicity (reactions within 60 minutes after each vaccination).
    • Local and systemic reactogenicity measured from Day 0 to Week 2 after each vaccination.
    • Any unsolicited adverse event between the first vaccination and four weeks after the third vaccination.
    • Any SAE occurring from the inclusion throughout the trial.


Secondary Outcome Measures:
  • The humoral and cellular responses [ Time Frame: 6 months after the last vaccination ] [ Designated as safety issue: No ]

    The humoral response to the vaccine antigens (DiCo1, DiCo2 and DiCo3) will be assessed by measuring the level of IgG by ELISA on samples obtained at screening visit Day 0, Week 4, 5, 8, 26, 27, 30 and 52.

    The cellular immune response will be assessed by measuring the T cell cytokine IL-5, and IFNg production by ELISpot following in vitro stimulation with the vaccine antigens on samples obtained at Day 0, Week 26, 30 and 52.



Other Outcome Measures:
  • The quality of the cellular and humoral immune responses [ Time Frame: Up to 6 months after the last vaccination ] [ Designated as safety issue: No ]

    The quality of the humoral immune response will be assessed by measuring:

    IgG1 and IgG3 subclasses by ELISA on samples obtained at Day 0 and Week 30. IgG responses to four natural allelic variants by ELISA on samples obtained at Days 0 and Week 30.

    An IFA will be employed to verify that the antibodies elicited by the vaccine recognize the native protein on merozoites on samples obtained Day 0 and Week 30.

    Competition ELISA with AMA1 antigen added as competitor at Week 30. The ability to inhibit parasite growth in vitro by a Growth Inhibition Assay (GIA) against at least 3 parasite strains on samples obtained at Day 0, Week 30 and 52.

    IgG avidity by ELISA on a panel of AMA1 alleles at Week 30.

    The quality of the cellular immune response will be assessed by measuring the production of a panel of T cell cytokines in the ELISpot supernatants by multiplex cytokine assay on samples obtained at Day 0, Week 26, 30 and 52.



Estimated Enrollment: 66
Study Start Date: January 2014
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AMA1-DiCo + Alhydrogel

Group A1 (15): European volunteer : AMA1-DiCo + Alhydrogel

AMA1-DiCo: 50µg

Alhydrogel® : 0.85 mg Al3+ per dose

Route : Intramuscular Vaccination schedule : Do, W4, W26

Biological: Group A1 : 50µg AMA1-DiCo + Alhydrogel
Experimental: AMA1-DiCo+ GLA-SE

Group A2 (15) : European volunteer : AMA1-DiCo + GLA-SE

AMA1-DiCo: 50µg

GLA-SE 2.5 µg GLA per dose

Route : Intramuscular Vaccination schedule : Do, W4, W26

Biological: Group A2 : 50 µg AMA1-DiCo+ GLA-SE
Experimental: AMA1-DiCo + GLA-SE

Group B1 (18) : African volunteer : AMA1-DiCo + GLA-SE

AMA1-DiCo: 50µg

GLA-SE 2.5 µg GLA per dose

Route : Intramuscular Vaccination schedule : Do, W4, W26

Biological: Group A2 : 50 µg AMA1-DiCo+ GLA-SE
Placebo Comparator: Placebo

Group B2 (18) : African volunteer : Placebo

Placebo : isotonic saline solution

Route : Intramuscular Vaccination schedule : Do, W4, W26

Biological: Group B2 : Placebo

Detailed Description:

The project aims are :

-To evaluate the safety of 50 µg AMA1-DiCo malaria vaccine candidate with GLA-SE and Alhydrogel® as adjuvant, in healthy European adults not previously exposed to the parasite Plasmodium falciparum and in healthy African adults exposed to the parasite.

T-o assess the humoral immune response to the vaccine antigens by measuring the level of IgG in all volunteers.

To assess the cellular immune response by measuring the T cell cytokines IL-5 and IFNγ production following in vitro stimulation with the vaccine antigens in all volunteers.

Design :

This trial is a staggered Phase Ia/Ib, Randomised, Double-blind, Multi-center Centre trial.

Two different adjuvants will be assessed, Alhydrogel® and GLA-SE. One dosage of 50 µg/3 injections of AMA1-DiCo will be evaluated for each adjuvant.

Sixty six (66) healthy volunteers will be included into the 2 following cohorts (A and B):

Cohort A: 30 Non-exposed European Volunteers (France) Cohort B: 36 Malaria Exposed African Volunteers (Burkina Faso)

The non-exposed European volunteers (cohort A) will be randomised in a 1:1 ratio into two groups of 15 volunteers per group.

The malaria exposed African volunteers (cohort B) will be randomised in a 1:1 ratio, into two groups of 18 volunteers per group.

European Volunteers: Cohort A (30):

Group A1 (15): 50µg AMA1-DiCo + Alhydrogel® Group A2 (15): 50 µg AMA1-DiCo+ GLA-SE

African Volunteers Cohort B (36) :

Group B1 (18): 50 µg AMA1-DiCo + GLA-SE Group B2 (18): Placebo (isotonic saline solution)

In order to start recruitment in cohort B (Africa), the safety will be evaluated on the data of all European volunteers until Day 7 after 1st immunisation of the last European volunteer Data will be presented to an Independent Data safety Monitoring Board (DSMB) that will be appointed for this trial

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age > 20 and < 45 years healthy female and male
  2. General good health based on history and clinical examination.
  3. Written informed consent obtained before any trial procedure.
  4. Female and male volunteers practicing contraception before and up to four (4) weeks after the third vaccination.
  5. Available to participate in follow-up for the duration of trial.
  6. Reachable by phone during the whole trial period.
  7. Volunteers should be affiliated to a social security regimen

Exclusion Criteria:

  1. Positive pregnancy test
  2. Active breast feeding
  3. Previous participation in any malaria vaccine trial
  4. History of blood transfusion within the last 6 months
  5. 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.
  6. Any clinically significant laboratory abnormalities on screened blood samples outside the normal range, as defined at the clinical trial site.
  7. Enrolment in any other clinical trial during the whole trial period
  8. 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 steroid use including intranasal.
  9. Any confirmed or suspected immunosuppressive or immunodeficiency condition during the whole trial period
  10. Volunteers unable to be closely followed for social, geographic or psychological reasons.
  11. Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the trial.
  12. History of anaphylaxis or Known severe hypersensitivity to any of the vaccine components (adjuvant or antigen or excipient)
  13. Vaccination or gamma globulin: 4 weeks prior and after each vaccination if a vaccination is necessary during this period, the volunteer will be withdrawn from the study.
  14. Positive HIV, HBV (Ag HBS) and HCV tests.
  15. History of malaria or travel in malaria endemic areas within the past twenty-six weeks.
  16. Positive serology for malaria antigen PfAMA-1
  17. Intention to travel to malaria endemic countries during the trial period.

    -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02014727

Contacts
Contact: Odile Launay 0033 158412860 odile.launay@cch.aphp.fr

Locations
Burkina Faso
CNRFP Recruiting
Ouagadougou, Burkina Faso
Contact: Sodiomon Sirima    Tel : + 226 50 32 46 95/6    s.sirima.cnlp@fasonet.bf;   
Contact: Adama Gansane    (00226)50-32-46-95 / 96    agansane.cnrfp@fasonet.bf   
Principal Investigator: Sodiomon Sirima         
France
CIC BT 505 de vaccinologie Cochin Pasteur Recruiting
Hôpital Cochin Bâtiment Lavoisier 27 rue du faubourg St Jacqu, Paris, France, 75014
Contact: Odile Launay, Professor    331 58 41 28 60    odile.launay@cch.aphp.fr   
Contact: Leila Kara    331 58 41 23 11    leila.kara@cch.aphp.fr   
Principal Investigator: Odile Launay         
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
EVI
BPRC
CIC COCHIN
CNRFP
Investigators
Principal Investigator: Odile Launay, Professor CIC BT505 Cochin Pasteur Groupe Hospitalier Cochin Broca Hotel Dieu. Bâtiment Lavoisier 27, rue du Faubourg Saint-Jacques 75679 PARIS Cedex 14, France odile.launay@cch.aphp.fr
Principal Investigator: Sodiomon Sirima, Doctor Centre National de Recherche et de Formation sur le Paludisme (CNRFP 01 BP 2208 Ouagadougou 01 1487, Avenue KumdaYonré, Burkina Faso s.sirima.cnlp@fasonet.bf
  More Information

No publications provided

Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT02014727     History of Changes
Other Study ID Numbers: C12-18 AMA-DiCo, 2013-001920-20
Study First Received: December 12, 2013
Last Updated: July 25, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
Burkina Faso : Direction Générale de la Pharmacie, du Médicament et des Laboratoires

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
Malaria vaccine
phase 1,
AMA1-DiCO

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Aluminum Hydroxide
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014