Safety and Immunogenicity of the Placental Malaria Vaccine Candidate PAMVAC Variously Adjuvanted (PAMVAC)

Study Description

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

Despite having developed robust acquired immunity against complications of malaria, women can return to a susceptible state during their first pregnancies and contribute significantly to the burden of severe malaria in highly endemic areas. Naturally acquired protection against placental malaria correlates with the presence of high concentration of immunoglobulin G molecules (IgGs) against VAR2CSA, a parasite protein of the var gene family that is essential for the binding of infected erythrocytes to CSA in the placenta.

To induce high concentrations of specific IgGs, subjects will receive escalating doses of PAMVAC vaccine antigen adjuvanted with Alhydrogel, Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE) or Glucopyranosyl Lipid Adjuvant-Liposome-QS-21 Formulation (GLA-LSQ). Three injections with the same dosage and adjuvant will be done, each 28 days apart (Day 0, 28 and 56). Control subjects will receive physiological saline instead of the vaccine and dose escalation will be staggered to ensure safety during the trial.

Condition or disease	Intervention/treatment	Phase
Malaria, Antepartum	Biological: PAMVAC; Biological: Alhydrogel; Biological: GLA-SE; Biological: GLA-LSQ; Other: Placebo	Phase 1

  Show Detailed Description

Study Design

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	66 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	Safety and Immunogenicity of the Placental Malaria Vaccine Candidate PAMVAC Adjuvanted With Alhydrogel, GLA-SE or GLA-LSQ in Healthy Malaria-Naïve Adults and Healthy, Lifelong Malaria-Exposed, Nulligravid Adult Women
Study Start Date :	May 2016
Actual Primary Completion Date :	November 10, 2017
Actual Study Completion Date :	November 10, 2017

Arms and Interventions

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: 1A - 20 µg PAMVAC + Alhydrogel; The study participant will get 20 µg of PAMVAC adjuvanted with Alhydrogel administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: Alhydrogel
Experimental: 2A - 20 µg PAMVAC + GLA-SE; The study participant will get 20 µg of PAMVAC adjuvanted with GLA-SE administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: GLA-SE
Experimental: 3A - 20 µg PAMVAC + GLA-LSQ; The study participant will get 20 µg of PAMVAC adjuvanted with GLA-LSQ administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: GLA-LSQ
Experimental: 4A - 50 µg PAMVAC + Alhydrogel; The study participant will get 50 µg of PAMVAC adjuvanted with Alhydrogel administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: Alhydrogel
Experimental: 5A - 50 µg PAMVAC + GLA-SE; The study participant will get 50 µg of PAMVAC adjuvanted with GLA-SE administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: GLA-SE
Experimental: 6A - 50 µg PAMVAC + GLA-LSQ; The study participant will get 50 µg of PAMVAC adjuvanted with GLA-LSQ administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: GLA-LSQ
Experimental: 1B - 50 µg PAMVAC + Alhydrogel; The study participant will get 50 µg of PAMVAC adjuvanted with Alhydrogel administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: Alhydrogel
Experimental: 2B - 50 µg PAMVAC + GLA-SE; The study participant will get 50 µg of PAMVAC adjuvanted with GLA-SE administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: GLA-SE
Experimental: 3B - 100 µg PAMVAC + Alhydrogel; The study participant will get 100 µg of PAMVAC adjuvanted with Alhydrogel administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: Alhydrogel
Experimental: 4B - 100 µg PAMVAC + GLA-SE; The study participant will get 100 µg of PAMVAC adjuvanted with GLA-SE administrated three times with each time 28 days interval (day 0-28-56)	Biological: PAMVAC; Biological: GLA-SE
Placebo Comparator: 5B - Placebo; The study participant will get Placebo (physiological saline solution) administrated three times with each time 28 days interval (day 0-28-56)	Other: Placebo

Outcome Measures

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Number and grade of adverse events (Grade 1-3 and serious adverse events) possibly, likely and definitely related to vaccination [ Time Frame: From the first administration of the interventions through study completion, an average of 1 and a half years ]

Secondary Outcome Measures :

1. Area under the curve of anti-PAMVAC IgG concentration [ Time Frame: Before first administration, 1, 4, 5, 8, 9, 12, 24 and 36 weeks after first administration ]

Eligibility Criteria

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 45 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• Healthy male and female volunteers aged 18-45 years.
• Able and willing (in the investigator's opinion) to comply with all trial requirements.
• General good health based on history and clinical examination
• Written informed consent
• Women only: Must agree to practice continuous effective contraception for the duration of the trial (a method which results in a low failure rate; i.e. less than 1% per year). Women will be counseled about effective contraception methods and, if required, can be provided with adequate contraceptives by the investigator team.
• Available to participate in follow up for the duration of trial (36 weeks following first injection)
• Reachable by phone during the whole trial period

Exclusion Criteria:

• Pregnancy, lactation or intention to become pregnant during the trial
• Previous participation in a malaria vaccine trial
• HIV infection
• Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
• Presence of autoimmune diseases requiring systemic treatment (e.g. rheumatic diseases)
• Use of immunoglobulins or blood products within 3 months prior to enrolment
• Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the trial period
• History of malaria or travel in malaria-endemic areas within the past 6 months
• Intention to travel to malaria endemic countries during the trial period
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
• History of serious psychiatric condition that may affect participation in the trial
• Any other serious chronic illness requiring hospital specialist supervision
• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 60 g (men) or 40 g (women) per day or a carbohydrate deficient transferrin (CDT) level ≥2.5%
• Suspected or known injecting drug abuse in the 5 years preceding enrolment
• Positive for hepatitis B surface antigen (HBs-antigen)
• Seropositive for hepatitis C virus (antibodies to HCV)
• Volunteers unable to be closely followed for social, geographic or psychological reasons
• Known hypersensitivity to any of the vaccine components (adjuvant or peptide)
• Any clinically significant abnormal finding on biochemistry or hematology blood tests, urine analysis or clinical examination
• History of seizure, except for sporadic febrile convulsions in childhood
• Any other significant disease, disorder or finding which, in the opinion of the investigator, may significantly increase the risk to the volunteer because of participation in the trial; affect the ability of the volunteer to participate in the trial or impair interpretation of the trial data.

Contacts and Locations

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Benin
Institut de Recherche Clinique du Benin (IRCB)
Abomey-Calavi, Benin

Sponsors and Collaborators

University Hospital Tuebingen

University of Copenhagen

Université d'Abomey-Calavi

European Malaria Vaccine Initiative

Institut de Recherche pour le Developpement

Expres2ion Biotechnologies APS

Investigators

Principal Investigator:	Benjamin G Mordmüller, MD	University Hospital Tübingen
Principal Investigator:	Saadou Issifou, MD	Université d'Abomey-Calavi

More Information

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	University Hospital Tuebingen
ClinicalTrials.gov Identifier:	NCT02647489 History of Changes
Other Study ID Numbers:	PAMVAC1_15
First Posted:	January 6, 2016
Last Update Posted:	June 25, 2018
Last Verified:	October 2016

Additional relevant MeSH terms:

Malaria; Protozoan Infections; Parasitic Diseases; Aluminum Hydroxide; Adjuvants, Immunologic	Immunologic Factors; Physiological Effects of Drugs; Antacids; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents