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

NCT02647489 | Completed Phase 1 DMC

• 1 other identifier: PAMVAC1_15
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria, Antepartum

Outcome Measures

Primary Outcomes (1)

• Number and grade of adverse events (Grade 1-3 and serious adverse events) possibly, likely and definitely related to vaccination

  From the first administration of the interventions through study completion, an average of 1 and a half years

Secondary Outcomes (1)

• Area under the curve of anti-PAMVAC IgG concentration

  Before first administration, 1, 4, 5, 8, 9, 12, 24 and 36 weeks after first administration

Study Arms (11)

1A - 20 µg PAMVAC + Alhydrogel

EXPERIMENTAL

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

2A - 20 µg PAMVAC + GLA-SE

EXPERIMENTAL

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

3A - 20 µg PAMVAC + GLA-LSQ

EXPERIMENTAL

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

4A - 50 µg PAMVAC + Alhydrogel

EXPERIMENTAL

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

5A - 50 µg PAMVAC + GLA-SE

EXPERIMENTAL

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

6A - 50 µg PAMVAC + GLA-LSQ

EXPERIMENTAL

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

1B - 50 µg PAMVAC + Alhydrogel

EXPERIMENTAL

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

2B - 50 µg PAMVAC + GLA-SE

EXPERIMENTAL

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

3B - 100 µg PAMVAC + Alhydrogel

EXPERIMENTAL

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

4B - 100 µg PAMVAC + GLA-SE

EXPERIMENTAL

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

5B - Placebo

PLACEBO COMPARATOR

The study participant will get Placebo (physiological saline solution) administrated three times with each time 28 days interval (day 0-28-56)

Other: Placebo

Interventions

PAMVAC BIOLOGICAL

1A - 20 µg PAMVAC + Alhydrogel; 1B - 50 µg PAMVAC + Alhydrogel; 2A - 20 µg PAMVAC + GLA-SE; 2B - 50 µg PAMVAC + GLA-SE; 3A - 20 µg PAMVAC + GLA-LSQ; 3B - 100 µg PAMVAC + Alhydrogel; 4A - 50 µg PAMVAC + Alhydrogel; 4B - 100 µg PAMVAC + GLA-SE; 5A - 50 µg PAMVAC + GLA-SE; 6A - 50 µg PAMVAC + GLA-LSQ

Alhydrogel BIOLOGICAL

1A - 20 µg PAMVAC + Alhydrogel; 1B - 50 µg PAMVAC + Alhydrogel; 3B - 100 µg PAMVAC + Alhydrogel; 4A - 50 µg PAMVAC + Alhydrogel

GLA-SE BIOLOGICAL

2A - 20 µg PAMVAC + GLA-SE; 2B - 50 µg PAMVAC + GLA-SE; 4B - 100 µg PAMVAC + GLA-SE; 5A - 50 µg PAMVAC + GLA-SE

GLA-LSQ BIOLOGICAL

3A - 20 µg PAMVAC + GLA-LSQ; 6A - 50 µg PAMVAC + GLA-LSQ

Placebo OTHER

5B - Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• University of Copenhagen: collaborator
• Université d'Abomey-Calavi: collaborator
• European Vaccine Initiative: collaborator
• Institut de Recherche pour le Developpement: collaborator
• ExpreS2ion Biotechnologies: collaborator

Study Sites (1)

Institut de Recherche Clinique du Benin (IRCB)

Abomey-Calavi, Benin

Location

Related Publications (3)

• Larsen MD, Lopez-Perez M, Dickson EK, Ampomah P, Tuikue Ndam N, Nouta J, Koeleman CAM, Ederveen ALH, Mordmuller B, Salanti A, Nielsen MA, Massougbodji A, van der Schoot CE, Ofori MF, Wuhrer M, Hviid L, Vidarsson G. Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination. Nat Commun. 2021 Oct 5;12(1):5838. doi: 10.1038/s41467-021-26118-w.

  PMID: 34611164 DERIVED

• 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.

  PMID: 33717176 DERIVED

• Mordmuller B, Sulyok M, Egger-Adam D, Resende M, de Jongh WA, Jensen MH, Smedegaard HH, Ditlev SB, Soegaard M, Poulsen L, Dyring C, Calle CL, Knoblich A, Ibanez J, Esen M, Deloron P, Ndam N, Issifou S, Houard S, Howard RF, Reed SG, Leroy O, Luty AJF, Theander TG, Kremsner PG, Salanti A, Nielsen MA. First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria. Clin Infect Dis. 2019 Oct 15;69(9):1509-1516. doi: 10.1093/cid/ciy1140.

  PMID: 30629148 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Aluminum Hydroxide; glucopyranosyl lipid-A

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes

Study Officials

• Benjamin G Mordmüller, MD

  University Hospital Tübingen

  PRINCIPAL INVESTIGATOR

• Saadou Issifou, MD

  Université d'Abomey-Calavi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 6, 2016
• Study Start: May 1, 2016
• Primary Completion: November 10, 2017
• Study Completion: November 10, 2017
• Last Updated: June 26, 2018

Record last verified: 2016-10

Locations

BE (1)