Clinical trial NCT02014727: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria, Falciparum
Keywords: Malaria vaccine
phase 1,
AMA1-DiCO
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: EVI Industries, Inc.
name: BPRC
name: Recherche Clinique Paris Descartes Necker Cochin Sainte Anne
name: Centre national de recherche et de formation sur le paludisme
First posted: 2013-12-18
Enrollment: 66
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

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Primary outcomes:
measure: Number of Adverse events
timeFrame: Up to four weeks after the third vaccination.
Secondary outcomes:
measure: The humoral and cellular responses
timeFrame: 6 months after the last vaccination
Other outcomes:
measure: The quality of the cellular and humoral immune responses
timeFrame: Up to 6 months after the last vaccination
Locations:
city: Ouagadougou
country: Burkina Faso
facility: CNRFP
city: Hôpital Cochin Bâtiment Lavoisier 27 rue du faubourg St Jacqu
country: France
facility: CIC BT 505 de vaccinologie Cochin Pasteur
state: Paris
Study officials:
affiliation: 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
name: Odile Launay, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: 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
name: Sodiomon Sirima, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sirima SB, Durier C, Kara L, Houard S, Gansane A, Loulergue P, Bahuaud M, Benhamouda N, Nebie I, Faber B, Remarque E, Launay O; AMA1-DiCo Study Group. Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel(R) in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial. Vaccine. 2017 Oct 27;35(45):6218-6227. doi: 10.1016/j.vaccine.2017.09.027. Epub 2017 Sep 22.