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Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults

ConditionMalaria Falciparum
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-45
SponsorSanaria Inc.

About this trial

This is a randomized, double-blind, placebo-controlled Phase 1 trial of Plasmodium falciparum (Pf) sporozoite (SPZ) late-arresting replication-competent (LARC) malaria vaccine (PfSPZ-LARC2 Vaccine) administered to healthy, malaria-naive study participants in Germany by direct venous inoculation (DVI) to determine safety, tolerability, and vaccine efficacy (VE) against controlled human malaria infection (CHMI). PfSPZ-LARC2 Vaccine contains a deletion of two genes, the Mei2 and LINUP genes, and undergoes developmental arrest in the late liver stages without releasing merozoites into the blood stream (blood stage parasites).

The primary objective of the study is to assess the safety and tolerability of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation, in the intention-to-treat (ITT) population.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Healthy adults (male or non-pregnant female) 18 to 45 years of age.

Able and willing to participate for the duration of the study.

Able and willing to provide written informed consent.

Physical examination and laboratory results without clinically significant findings.

Disqualifiers

Unable to provide informed consent including inability to pass the test of understanding.

Receipt of a malaria vaccine in a prior clinical trial.

History of a splenectomy or sickle cell disease.

History of a neurologic disorder (including non-febrile seizures or complex febrile seizures) or formal history of migraine headache.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Normal Saline (Placebo)

    Other intervention

    The blinded control group (n = 6) of the main cohort will receive normal saline as placebo, also by DVI.

  • PfSPZ-LARC2 Vaccine

    Biological/Vaccine

    Plasmodium falciparum (Pf) sporozoite (SPZ) late-arresting replication-competent (LARC) malaria vaccine (PfSPZ-LARC2 Vaccine) contains a deletion of two genes, the Mei2 and LINUP genes, and undergoes developmental arrest in the late liver stages without releasing merozoites into the blood stream (blood stage parasites).

  • PfSPZ Challenge (NF54)

    Biological/Vaccine

    Main cohort participants will undergo homologous CHMI using DVI of 3.2x10\^3 PfSPZ of PfSPZ Challenge (NF54), which are infectious cryopreserved Pf sporozoites.

Treatment groups

58 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Part A Sentinel Group PfSPZ-LARC2Experimental treatment 1 intervention
Group B: Part A Main Cohort PfSPZ-LARC2 verum groupExperimental treatment 2 interventions
Group C: Part A Main Cohort Normal Saline control groupPlacebo comparator 2 interventions
Group D: Part B Sentinel Group PfSPZ-LARC2Experimental treatment 1 intervention
Group E: Part B Main Cohort PfSPZ-LARC2 verum groupExperimental treatment 2 interventions
Group F: Part B Main Cohort Normal Saline control groupPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

Safety and tolerability of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation, in the intention-to-treat (ITT) population: infection

Number of trial participants with blood stage infection during the first 28 days after immunization.

Time frame
28 days after immunization
2

Safety and tolerability of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation, in the intention-to-treat (ITT) population: related AEs

Incidence of at least possibly related grade 3 solicited adverse events (AE) and grade 3 abnormal laboratory values occurring in the 7 days after injection of PfSPZ-LARC2 Vaccine .

Time frame
7 days after injection of PfSPZ-LARC2 Vaccine
3

Safety and tolerability of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation, in the intention-to-treat (ITT) population: related SAEs

Incidence of related serious adverse events (SAEs)

Time frame
Time of first immunization to the end of the study

Secondary outcomes

1

Vaccine Efficacy (VE) (1 minus the risk ratio) against homologous CHMI with PfSPZ Challeng(NF54) conducted 12 weeks after 3rd immunization in the modified ITT (mITT) population

Proportion of protected volunteers following CHMI. Protection is defined as the absence of parasitemia in the peripheral blood for +21 days following CHMI with PfSPZ Challenge (NF54) in volunteers who received PfSPZ-LARC2 Vaccine.

Time frame
21 days following CHMI
2

Humoral immune responses to PfCSP and their relationship to VE.

Antibody responses as measured by PfCSP ELISA.

Time frame
The day before immunization until 21 days post CHMI

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sanaria Inc.

Lead sponsor

Universitätsklinikum Tübingen, Institut für Tropenmedizin Wilhelmstrasse

Collaborator

UCLA David Geffen School of Medicine and Fielding School of Public Health

Collaborator

Stanford University

Collaborator

Leiden University

Collaborator

Source ClinicalTrials.gov
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