Clinical trial NCT02658253: Trial to Evaluate the Safety and Immunogenicity of a Placental Malaria Vaccine Candidate (PRIMVAC ) in Healthy Adults
Official title: Phase Ia/Ib, Randomized, Double Blinded, Dose Escalation Trial to Evaluate the Safety and Immunogenicity in Healthy European and Burkinabe Adults of a Placental Malaria Vaccine Candidate (PRIMVAC) Formulated With Alhydrogel ® or GLA-SE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Keywords: Placental malaria vaccine
Plasmodium
PRIMALVAC
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: European Vaccine Initiative
name: Recherche Clinique Paris Descartes Necker Cochin Sainte Anne
name: Centre national de recherche et de formation sur le paludisme
name: EUCLID Clinical Trial Platform
First posted: 2016-01-18
Enrollment: 68
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective of the study is to evaluate the safety of 3 different dosages (20µg - 50µg and 100µg) of a placental malaria vaccine candidate (PRIMVAC vaccine) adjuvanted either with Alhydrogel® or GLA-SE, and administered at D0, D28 and D56 in healthy European and Burkinabe adults.

The safety and the tolerability of the vaccine will be assessed on the rate of solicited and unsolicited events/reactions The safety profile will included 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:

* Primary objective is to evaluate the safety of 3 different dosages (20µg - 50µg and 100µg) of the PRIMVAC vaccine adjuvanted either with Alhydrogel® or GLA-SE, and administered at D0, D28 and D56 in healthy European and Burkinabe adults.
* Secondary objectives are to assess:

  * the humoral immune response to the PRIMVAC vaccine antigen (VAR2CSA) by measuring the variation in the level of total IgG and the level of the isotypic subtypes capable of recognizing the native antigen.
  * the cellular immune response by measuring:

    * the number of T cell secreting IL5 and IFNg following an ex-vivo stimulation with the vaccine antigen
    * the B lymphocyte phenotypes isolated from PBMC
* Exploratory objectives are:

  * To explore the quality of the humoral immune response by the measure of the capability of the antibodies specific to the vaccine antigen to:

    * Cross-react with different VAR2CSA variants expressed on the surface of erythrocytes infected by various strains of Plasmodium falciparum,
    * Inhibit interactions between parasitized erythrocytes expressing different VAR2CSA variants and Chondroitin Sulfate A (receptor involved in placental sequestration),
    * Promote opsonic phagocytosis of parasitized erythrocytes with various strains of Plasmodium falciparum expressing different VAR2CSA variants
  * To explore the quality of the cellular immune response induced by the vaccine antigen by the quantitation of a large panel of cytokines in the ELISpot supernatants.

Eligibility criteria: Inclusion criteria (FRANCE):

* Written informed consent (must be obtained prior initiation of any study related intervention)
* Female of age ≥18 years to ≤35 years
* Healthy as a result of review of medical history and/or clinical examination at the time of screening and clinical judgment of the investigator
* Available for the duration of the trial (15 months)
* Willingness to use reliable contraceptive methods such as: birth control pills or birth control patches or vaginal ring, diaphragm, IUD (intrauterine device), condom, progestin implant or injection, or surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation) prior to enrollment at V0 and up to 4 weeks after last vaccination (V6)
* Volunteer reachable by phone during the entire study duration
* Individuals affiliated to a social security regimen
* Volunteer registered in the French Health ministry computerized file and authorized to participate in a clinical trial

Exclusion criteria (FRANCE):

* Pregnancy ongoing as determined by a positive blood test or breastfeeding or lactation.
* Intention to become pregnant during the trial
* Volunteers who are not able to understand and to follow all required study procedures for the whole period of the study in the opinion of the investigator.
* Volunteers with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
* Volunteers participating in any clinical trial with another investigational product 28 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.
* History of psychiatric condition that may affect participation in the study (i.e. depression, anti-depressant treatment).
* Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the study data based on investigator's judgment.
* Any history of malaria infection.
* Travel to a malaria endemic region during the study period or within the six months preceding enrolment in the study.
* Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
* History of a serious adverse reaction to any vaccine, including Guillain-Barre Syndrome.
* Administration or planned administration of a vaccine or gammaglobulin not foreseen by the clinical trial protocol within 30 days prior to the first immunization and up to 4 weeks after the last immunization.
* Volunteers with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
* Administration of immunoglobulins and/or any blood products within the three months preceding the inclusion.
* Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 3 months (inhaled and topical steroids are allowed)
* Seropositive for hepatitis B virus surface antigen (HBsAg)
* Seropositive for hepatitis C virus (antibodies to HCV)
* Seropositive for human immunodeficiency virus (antibodies to HIV 1-2)
* Any other serious chronic illness requiring hospital specialist supervision.
* Any clinically significant abnormal finding on screening biochemistry or hematology blood tests or urinalysis
* Symptoms, physical signs or laboratory values suggestive of systemic disorders, including infectious renal, hepatic, cardiovascular, pulmonary, cutaneous, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the volunteers.
* Volunteer under guardianship or legal incapacitation.

Inclusion criteria (BURKINA FASO):

* Written informed consent (must be obtained prior initiation of any study related intervention)
* Nulligest Female of age ≥18 years to ≤35 years
* Healthy as a result of review of medical history and/or clinical examination at the time of screening and clinical judgment of the investigator
* Available for the duration of the trial (15 months)
* Willingness to use reliable contraceptive methods such as: birth control pills or birth control patches or vaginal ring, diaphragm, IUD (intrauterine device), condom, progestin implant or injection, or surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation) prior to enrollment at V0 and up to 4 weeks after last vaccination (V6)

Exclusion criteria (BURKINA FASO):

* Pregnancy ongoing as determined by a positive urinary test
* Intention to become pregnant during the trial
* Volunteers who are not able to understand and to follow all required study procedures for the whole period of the study in the opinion of the investigator.
* Volunteers with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
* Volunteers participating in any clinical trial with another investigational product 28 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.
* History of psychiatric condition that may affect participation in the study (i.e. depression, anti-depressant treatment).
* Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data, based on investigator's judgment.
* Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
* History of a serious adverse reaction to any vaccine, including Guillain-Barre syndrome.
* Administration or planned administration of a vaccine or gammaglobulin not foreseen by the clinical trial protocol within 30 days prior to the first immunization and up to 4 weeks after the last immunization.
* Volunteers with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
* Administration of immunoglobulins and/or any blood products within the three months preceding the inclusion.
* Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 3 months (inhaled and topical steroids are allowed).
* Seropositive for hepatitis B virus surface antigen (HBsAg).
* Seropositive for hepatitis C virus (antibodies to HCV).
* Seropositive for human immunodeficiency virus (antibodies to HIV 1-2).
* Any other serious chronic illness requiring hospital specialist supervision.
* Any clinically significant abnormal finding on screening biochemistry or hematology blood tests or urinalysis
* Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, cutaneous, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the volunteers.
* Volunteer under guardianship or legal incapacitation.

Primary outcomes:
measure: Proportion of volunteers with treatment-related adverse events as assessed by FDA scale and the INYVAX EC FP7 Brighton Collaboration Foundation
timeFrame: 35 days
Secondary outcomes:
measure: Proportion of volunteer with at least one Serious Adverse Event Following Immunization (SAEFI) for the entire duration of the study
timeFrame: 14 months
measure: Proportion of volunteer with at least one of Adverse Event Following Immunization (AEFI) measured until 1 month post-dose 3
timeFrame: 3 months
measure: Proportion of volunteer with at least one Adverse Event Following Immunization (AEFI) measured between M3 and the end of the study (only phase Ia)
timeFrame: 11 months
measure: Variation in humoral immune response to the vaccine antigen assessed by ELISA
timeFrame: 14 months
measure: Variation in humoral immune response to the vaccine antigen assessed by ELISA
timeFrame: 3 months
measure: Cellular immune responses to the vaccine antigen by Elispot
timeFrame: 63 days
measure: Cellular immune responses to the vaccine antigen by FACS
timeFrame: 63 days
Other outcomes:
measure: Quality of the humoral immune responses
timeFrame: 3 months
measure: Quality of the cellular immune response by the Multiplex technology
timeFrame: 63 days
Locations:
city: Ouagadougou
country: Burkina Faso
facility: CNRFP
city: Paris
country: France
facility: CIC 1417
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Odile Launay, Professor
role: STUDY_CHAIR
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Benoit GAMAIN, Dr
role: STUDY_DIRECTOR
affiliation: Centre national de recherche et de formation sur le paludisme
name: Sodiomon SIRIMA, Dr
role: STUDY_CHAIR
References:
citation: Sirima SB, Richert L, Chene A, Konate AT, Campion C, Dechavanne S, Semblat JP, Benhamouda N, Bahuaud M, Loulergue P, Ouedraogo A, Nebie I, Kabore M, Kargougou D, Barry A, Ouattara SM, Boilet V, Allais F, Roguet G, Havelange N, Lopez-Perez E, Kuppers A, Konate E, Roussillon C, Kante M, Belarbi L, Diarra A, Henry N, Soulama I, Ouedraogo A, Esperou H, Leroy O, Batteux F, Tartour E, Viebig NK, Thiebaut R, Launay O, Gamain B. PRIMVAC vaccine adjuvanted with Alhydrogel or GLA-SE to prevent placental malaria: a first-in-human, randomised, double-blind, placebo-controlled study. Lancet Infect Dis. 2020 May;20(5):585-597. doi: 10.1016/S1473-3099(19)30739-X. Epub 2020 Feb 4.
citation: Gamain B, Chene A, Viebig NK, Tuikue Ndam N, Nielsen MA. Progress and Insights Toward an Effective Placental Malaria Vaccine. Front Immunol. 2021 Feb 25;12:634508. doi: 10.3389/fimmu.2021.634508. eCollection 2021.