Health Trials

Challenge Trial of PfSPZ-LARC2 Vaccine in Burkina Faso

ConditionMalaria (Plasmodium Falciparum)
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-50
SponsorSanaria Inc.

About this trial

This is a randomized, double-blind, placebo-controlled, Phase 1 trial of Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) malaria vaccine (Sanaria® PfSPZ-LARC2 Vaccine) administered to healthy, malaria-exposed adults by direct venous inoculation (DVI) to determine safety, immunogenicity, and efficacy against controlled human malaria infection (CHMI).

The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double deletion of the genes encoding the Mei2 and LINUP proteins, both of which are required for transition from liver to blood stage malaria. As a result, mei2-/linup- parasites undergo developmental arrest in the late liver stages without releasing merozoites into the blood stream. No blood stage parasites are produced, either asexual or sexual, and the parasite life cycle does not progress.

CHMI will be performed using PfSPZ Challenge (NF54), composed of PfSPZ that are genetically intact and fully infectious. Because PfSPZ-LARC2 vaccine is also based on the Pf strain NF54, CHMI using PfSPZ Challenge (NF54) is considered homologous to the vaccine. It will be performed 6 weeks after the single administration of PfSPZ-LARC2 Vaccine or normal saline placebo (with an option to shorten the interval to 4 weeks if logistical issues arise, such as a risk that CHMI follow-up will overlap with the rainy season).

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Healthy males and females, based on clinical and laboratory findings (note: an effort will be made to recruit roughly equal numbers of males and females, although a balanced sex ratio is not required)

From 18 to 50 years of age

Adults with a Body Mass Index (BMI) 18 to 30 Kg/m²

Residence in the study area for the duration of the study

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

Parallel

Treatments tested in this trial

  • PfSPZ-LARC2 Vaccine

    Biological/Vaccine

    PfSPZ-LARC2 Vaccine is composed of aseptic, purified, vialed, cryopreserved, genetically altered PfNF54 sporozoites (SPZ) that are stored in liquid nitrogen vapor phase (LNVP).

  • PfSPZ Challenge

    Biological/Vaccine

    PfSPZ Challenge (NF54) is composed of PfSPZ that are genetically intact and fully infectious. The aseptic, purified, vialed, cryopreserved PfNF54 sporozoites (SPZ) are stored in liquid nitrogen vapor phase (LNVP).

  • Normal Saline

    Other intervention

    saline control comparator

Treatment groups

45 Participants
are divided into 3 treatment groups
Group A: Group 1 Low dose Vaccine groupExperimental treatment 2 interventions
Group B: Group 2 High Dose Vaccine groupExperimental treatment 2 interventions
Group C: Group 3 controlPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

Efficacy of PfSPZ-LARC2 Vaccine against infection with Plasmodium falciparum malaria (defined as asexual parasitemia) after Controlled Human Malaria Infection (CHMI)

Frequency of P. falciparum asexual parasitemia in each vaccine group relative to controls after controlled human malaria infection (CHMI). Participants will be followed as outpatients for malaria diagnosis, treatment, and follow-up for four weeks after CHMI until day CHMI+28. Malaria positivity will be determined in real time by TBS microscopy read immediately and with qPCR diagnostics based on concurrent DBS completed retrospectively.

Time frame
Study day 43 (day of CHMI) to Study day 71 (28 days after CHMI)
2

Safety and tolerability of PfSPZ-LARC2 Vaccine administration in malaria-exposed Burkinabe adults- grade 3 solicited AEs

Incidence of grade 3 solicited adverse events (AEs) in the 14 days after PfSPZ-LARC2 Vaccine administration

Time frame
Study day 1 (day of immunization) to study day 15
3

Safety and tolerability of PfSPZ-LARC2 Vaccine administration in malaria-exposed Burkinabe adults- grade 3 unsolicited AEs

Incidence of grade 3 unsolicited AEs in the 28 days after PfSPZ-LARC2 Vaccine administration

Time frame
study day 1 (day of immunization) to study day 29
4

Safety and tolerability of PfSPZ-LARC2 Vaccine administration in malaria-exposed Burkinabe adults- grade 3 laboratory AEs

Incidence of grade 3 abnormal laboratory values one week after PfSPZ-LARC2 Vaccine administration

Time frame
study day 1 (day of immunization) to study day 8

Secondary outcomes

1

Humoral immune responses to PfCSP (circumsporozoite protein) after vaccination

Anti-P. falciparum circumsporozoite protein antibody levels measured by ELISA two weeks after vaccination.

Time frame
study day 1 to study day 71
2

Correlation of humoral immune responses to PfCSP (anti-PfCSP antibody levels 2 weeks after immunization) with protection (frequency of Pf asexual parasitemia in vaccinees relative to controls after CHMI)

Statistical assessment of associations of humoral responses (level of anti-PfCSP antibodies) with protection (frequency of Pf asexual parasitemia) - specifically, the correlation between anti-PfCSP antibody levels, as measured by ELISA two weeks after vaccination, with vaccine efficacy, as measured by frequency of P. falciparum asexual parasitemia in each vaccine group relative to controls after CHMI. Participants will be followed as outpatients for malaria diagnosis, treatment, and follow-up for four weeks after CHMI until day CHMI+28. Malaria positivity will be determined in real time by TBS microscopy read immediately and with qPCR diagnostics based on concurrent DBS completed retrospectively.

Time frame
Study day 1 to Study day 71

Other outcomes

Sponsors and contacts

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

Sanaria Inc.

Lead sponsor

University of Maryland, Baltimore

Collaborator

Seattle Children's Hospital

Collaborator

University of California, Los Angeles

Collaborator

Groupe de Recherche Action en Sante

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: