Trial to Evaluate the Safety and Immunogenicity of a Placental Malaria Vaccine Candidate (PRIMVAC ) in Healthy Adults
- Conditions
- Malaria
- Interventions
- Registration Number
- NCT02658253
- Lead Sponsor
- Institut National de la Santé Et de la Recherche Médicale, France
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 68
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B2:Primvac 50 µg +GLA-SE GLA-SE Group B2: 6 European volunteers 0.5 ml intramuscular injection:50 µg Primvac+ 2.5 µg GLA-SE Vaccination schedule: D0, D28 and D56 Group A2:Primvac 20 µg +GLA-SE GLA-SE Group A2: 3 European volunteers 0.5 ml intramuscular injection:20 µg Primvac+ 2.5 µg GLA-SE Vaccination schedule: D0, D28 and D56 Group A1:Primvac 20 µg +alhydrogel Alhydrogel Group A1: 3 European volunteers 0.5 ml intramuscular injection: 20 µg Primvac+ 0.85 mg Alhydrogel® Vaccination schedule: D0, D28 and D56 Group C1:Primvac 50 µg +alhydrogel Alhydrogel Group C1: 10 African volunteers 0.5 ml intramuscular injection: 50 µg Primvac+ 0.85 mg Alhydrogel® Vaccination schedule: D0, D28 and D56 Group A1:Primvac 20 µg +alhydrogel PRIMVAC Group A1: 3 European volunteers 0.5 ml intramuscular injection: 20 µg Primvac+ 0.85 mg Alhydrogel® Vaccination schedule: D0, D28 and D56 Group B1:Primvac 50 µg +alhydrogel PRIMVAC Group B1: 6 European volunteers 0.5 ml intramuscular injection: 50 µg Primvac+ 0.85 mg Alhydrogel® Vaccination schedule: D0, D28 and D56 Group D1:Primvac 100 µg +alhydrogel Alhydrogel Group D1: 10 African volunteers 0.6 ml intramuscular injection: 100µg Primvac+ 0.85 mg Alhydrogel® Vaccination schedule: D0, D28 and D56 Group D3: placebo Placebo Group D3: 5 African volunteers 0.6 ml intramuscular injection: NaCl 0.9% (placebo) Vaccination schedule: D0, D28 and D56 Group A2:Primvac 20 µg +GLA-SE PRIMVAC Group A2: 3 European volunteers 0.5 ml intramuscular injection:20 µg Primvac+ 2.5 µg GLA-SE Vaccination schedule: D0, D28 and D56 Group D1:Primvac 100 µg +alhydrogel PRIMVAC Group D1: 10 African volunteers 0.6 ml intramuscular injection: 100µg Primvac+ 0.85 mg Alhydrogel® Vaccination schedule: D0, D28 and D56 Group D2: Primvac 100 µg +GLA-SE PRIMVAC Group D2: 10 African volunteers 0.6 ml intramuscular injection: 100 µg Primvac+ 2.56 µg GLA-SE Vaccination schedule: D0, D28 and D56 Group D2: Primvac 100 µg +GLA-SE GLA-SE Group D2: 10 African volunteers 0.6 ml intramuscular injection: 100 µg Primvac+ 2.56 µg GLA-SE Vaccination schedule: D0, D28 and D56 Group C2: Primvac 50 µg +GLA-SE GLA-SE Group C2: 10 African volunteers 0.5 ml intramuscular injection: 50 µg Primvac+ 2.5 µg GLA-SE Vaccination schedule: D0, D28 and D56 Group C3: Placebo Placebo Group C3: 5 African volunteers 0.5 ml intramuscular injection: NaCl 0.9% (placebo) Vaccination schedule: D0, D28 and D56 Group B2:Primvac 50 µg +GLA-SE PRIMVAC Group B2: 6 European volunteers 0.5 ml intramuscular injection:50 µg Primvac+ 2.5 µg GLA-SE Vaccination schedule: D0, D28 and D56 Group C1:Primvac 50 µg +alhydrogel PRIMVAC Group C1: 10 African volunteers 0.5 ml intramuscular injection: 50 µg Primvac+ 0.85 mg Alhydrogel® Vaccination schedule: D0, D28 and D56 Group C2: Primvac 50 µg +GLA-SE PRIMVAC Group C2: 10 African volunteers 0.5 ml intramuscular injection: 50 µg Primvac+ 2.5 µg GLA-SE Vaccination schedule: D0, D28 and D56 Group B1:Primvac 50 µg +alhydrogel Alhydrogel Group B1: 6 European volunteers 0.5 ml intramuscular injection: 50 µg Primvac+ 0.85 mg Alhydrogel® Vaccination schedule: D0, D28 and D56
- Primary Outcome Measures
Name Time Method Proportion of volunteers with treatment-related adverse events as assessed by FDA scale and the INYVAX EC FP7 Brighton Collaboration Foundation 35 days Grade 3 or higher clinical or laboratory ARI and persisting at Grade 3 for \> 48 hours between D0 and D35.
- Secondary Outcome Measures
Name Time Method Proportion of volunteer with at least one Serious Adverse Event Following Immunization (SAEFI) for the entire duration of the study 14 months clinical and biological SAEFI and SARI (Serious Adverse Reaction following Immunization (SARI) measured at any time during the volunteer follow-up
Proportion of volunteer with at least one Adverse Event Following Immunization (AEFI) measured between M3 and the end of the study (only phase Ia) 11 months Immediate AEFI (within 1h following vaccination) as well as unrelated, Related or possibly related solicited and unsolicited AEFI
Variation in humoral immune response to the vaccine antigen assessed by ELISA 3 months The level (g/l) of the isotypic subtypes (IgG1, IgG2, IgG3, IgG4) between D0 and the post-vaccination time point M3
Proportion of volunteer with at least one of Adverse Event Following Immunization (AEFI) measured until 1 month post-dose 3 3 months Immediate AEFI (within 1h following vaccination) as well as unrelated, Related or possibly related solicited and unsolicited AEFI
Cellular immune responses to the vaccine antigen by Elispot 63 days The median number of spots by ELISpot assay, allowing the counting of IL5 and IFNg secreting cells following an ex-vivo stimulation of PBMC with the vaccine antigen at V0, and 7 days post-dose 1 and 3 (D0- D7 and M2+7D)
Cellular immune responses to the vaccine antigen by FACS 63 days CD19, IgD, CD27, CD38, CD24 and CD43 B lymphocytes subpopulations will be isolated from PBMC at D0 and M2+7D. The data will be expressed for each phenotype as the median percentage of subpopulations among total CD19 B lymphocytes
Trial Locations
- Locations (2)
CNRFP
🇧🇫Ouagadougou, Burkina Faso
CIC 1417
🇫🇷Paris, France