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Trial to Evaluate the Safety and Immunogenicity of a Placental Malaria Vaccine Candidate (PRIMVAC ) in Healthy Adults (PRIMALVAC)

This study is currently recruiting participants.
Verified January 2016 by Institut National de la Santé Et de la Recherche Médicale, France
Sponsor:
ClinicalTrials.gov Identifier:
NCT02658253
First Posted: January 18, 2016
Last Update Posted: March 24, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
EVI
CIC COCHIN
CNRFP
EUCLID
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France
  Purpose

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


Condition Intervention Phase
Malaria Biological: PRIMVAC Biological: GLA-SE Biological: Alhydrogel Biological: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
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

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:
  • Proportion of volunteers with treatment-related adverse events as assessed by FDA scale and the INYVAX EC FP7 Brighton Collaboration Foundation [ Time Frame: 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:
  • Proportion of volunteer with at least one Serious Adverse Event Following Immunization (SAEFI) for the entire duration of the study [ Time Frame: 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 of Adverse Event Following Immunization (AEFI) measured until 1 month post-dose 3 [ Time Frame: 3 months ]
    Immediate AEFI (within 1h following vaccination) as well as unrelated, Related or possibly related solicited and unsolicited AEFI

  • Proportion of volunteer with at least one Adverse Event Following Immunization (AEFI) measured between M3 and the end of the study (only phase Ia) [ Time Frame: 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 [ Time Frame: 14 months ]
    The level of total IgG (g/l): between D0 and the post-vaccination time points M1, M1+7D, M2, M2+7D, M3, M6 and M14

  • Variation in humoral immune response to the vaccine antigen assessed by ELISA [ Time Frame: 3 months ]
    The level (g/l) of the isotypic subtypes (IgG1, IgG2, IgG3, IgG4) between D0 and the post-vaccination time point M3

  • Cellular immune responses to the vaccine antigen by Elispot [ Time Frame: 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 [ Time Frame: 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


Other Outcome Measures:
  • Quality of the humoral immune responses [ Time Frame: 3 months ]

    Will be assessed by measuring the capability of the specific vaccine antigen plasma IgGs to:

    • Cross-react with different VAR2CSA variants expressed on the surface of erythrocytes parasitized by various strains of Plasmodium falciparum by flow cytometry.
    • Inhibit interactions between parasitized erythrocytes expressing different VAR2CSA variants and Chondroitin Sulfate A in static and flow conditions
    • Promote opsonic phagocytosis of parasitized erythrocytes with various strains of Plasmodium falciparum expressing different VAR2CSA variants, using the THP1 cell line. Ingestion of fluorescently labeled parasitized erythrocytes by THP1 cells will be assessed by flow cytometry.

  • Quality of the cellular immune response by the Multiplex technology [ Time Frame: 63 days ]
    Will be assessed by measuring the quantitation of a large panel of cytokines in ELISpot supernatants will be performed at D0- D7 and M2+7D. The difference of the cytokines concentrations (expressed as MFI) between the pre-vaccination samples and the samples collected at D7 and M2+7D will be calculated.


Estimated Enrollment: 68
Study Start Date: January 2016
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A1:Primvac 20 µg +alhydrogel

Group A1: 3 European volunteers 0.5 ml intramuscular injection: 20 µg Primvac+ 0.85 mg Alhydrogel®

Vaccination schedule: D0, D28 and D56

Biological: PRIMVAC
3 different dosages of VAR2CSA protein (20µg - 50µg and 100µg)
Biological: Alhydrogel
0.85 mg og Aluminium content
Experimental: Group A2:Primvac 20 µg +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
Biological: PRIMVAC
3 different dosages of VAR2CSA protein (20µg - 50µg and 100µg)
Biological: GLA-SE
2.56 µg of GLA content
Experimental: Group B1:Primvac 50 µg +alhydrogel

Group B1: 6 European volunteers 0.5 ml intramuscular injection: 50 µg Primvac+ 0.85 mg Alhydrogel®

Vaccination schedule: D0, D28 and D56

Biological: PRIMVAC
3 different dosages of VAR2CSA protein (20µg - 50µg and 100µg)
Biological: Alhydrogel
0.85 mg og Aluminium content
Experimental: Group B2:Primvac 50 µg +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
Biological: PRIMVAC
3 different dosages of VAR2CSA protein (20µg - 50µg and 100µg)
Biological: GLA-SE
2.56 µg of GLA content
Experimental: Group C1:Primvac 50 µg +alhydrogel

Group C1: 10 African volunteers 0.5 ml intramuscular injection: 50 µg Primvac+ 0.85 mg Alhydrogel®

Vaccination schedule: D0, D28 and D56

Biological: PRIMVAC
3 different dosages of VAR2CSA protein (20µg - 50µg and 100µg)
Biological: Alhydrogel
0.85 mg og Aluminium content
Experimental: Group C2: Primvac 50 µg +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

Biological: PRIMVAC
3 different dosages of VAR2CSA protein (20µg - 50µg and 100µg)
Biological: GLA-SE
2.56 µg of GLA content
Placebo Comparator: Group C3: Placebo

Group C3: 5 African volunteers 0.5 ml intramuscular injection: NaCl 0.9% (placebo)

Vaccination schedule: D0, D28 and D56

Biological: Placebo
0.9% Na cl
Experimental: Group D1:Primvac 100 µg +alhydrogel

Group D1: 10 African volunteers 0.6 ml intramuscular injection: 100µg Primvac+ 0.85 mg Alhydrogel®

Vaccination schedule: D0, D28 and D56

Biological: PRIMVAC
3 different dosages of VAR2CSA protein (20µg - 50µg and 100µg)
Biological: Alhydrogel
0.85 mg og Aluminium content
Experimental: Group D2: Primvac 100 µg +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

Biological: PRIMVAC
3 different dosages of VAR2CSA protein (20µg - 50µg and 100µg)
Biological: GLA-SE
2.56 µg of GLA content
Placebo Comparator: Group D3: placebo

Group D3: 5 African volunteers 0.6 ml intramuscular injection: NaCl 0.9% (placebo)

Vaccination schedule: D0, D28 and D56

Biological: Placebo
0.9% Na cl

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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02658253


Contacts
Contact: Odile LAUNAY, Professor +33 (0)158412858 odile.launay@cch.aphp.fr
Contact: Benoit GAMAIN, Dr +33 (0)1 44 49 31 47 benoit.gamain@inserm.fr

Locations
Burkina Faso
CNRFP Not yet recruiting
Ouagadougou, Burkina Faso, BP 2208
Contact: Sodiomon Sirima, Dr    +22650324695    s.sirima.cnlp@fasonet.bf   
Contact: Amadou KONATE, Dr    +22670262965    a.konate.cnlp@fasonet.bf   
France
CIC 1417 Recruiting
Paris, France, 75679
Contact: Odile LAUNAY, Pr    +33(0)158412858    odile.launay@cch.aphp.fr   
Principal Investigator: Pierre Loulergue, Dr         
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
EVI
CIC COCHIN
CNRFP
EUCLID
Investigators
Study Chair: Odile Launay, Professor Institut National de la Santé Et de la Recherche Médicale, France
Study Director: Benoit GAMAIN, Dr Institut National de la Santé Et de la Recherche Médicale, France
Study Chair: Sodiomon SIRIMA, Dr CNRFP
  More Information

Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT02658253     History of Changes
Other Study ID Numbers: C14-60
2015-002246-31 ( EudraCT Number )
First Submitted: January 7, 2016
First Posted: January 18, 2016
Last Update Posted: March 24, 2016
Last Verified: January 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
Placental malaria vaccine
Plasmodium
PRIMALVAC

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