Field Trial of PfSPZ-LARC2 Vaccine in Burkinabe Adults
ConditionMalaria (Plasmodium Falciparum)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-50
SponsorSanaria Inc.
About this trial
This is a phase 2 clinical trial of a Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) vaccine (Sanaria® PfSPZ-LARC2 Vaccine) that will assess field efficacy in Africa.
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. Because Pf parasites with the LARC phenotype replicate in the liver before disintegrating, they amplify and diversify parasite protein expression and are expected to be a potent immunogen to induce anti-malarial immunity, equaling or exceeding the potency and efficacy of the replication-competent chemo-attenuated Sanaria® PfSPZ-CVac (chloroquine) vaccine approach. Because the parasites are intrinsically attenuated, they are expected to be safe and well tolerated, similar to radiation-attenuated Sanaria® PfSPZ Vaccine, to the replication deficient, early arresting PfSPZ-GA1 Vaccine, and to the single-gene(mei2)-deleted GA2 (LARC1) parasites tested at the Leiden University Medical Center that provided 90% protection against CHMI after a single dose.
The active treatments to be assessed for efficacy are one immunization of 6.0x10\^5 PfSPZ or two immunizations with 4.0x10\^5 PfSPZ of PfSPZ-LARC2 Vaccine four weeks apart, timed so that the immunization of the one dose regimen coincides with the second immunization of the two dose regimen.
The alternative treatment is immunization with normal saline (placebo group), which is indistinguishable from the test article.
The primary variable of interest is whether and when trial participants develop Pf malaria parasitemia during surveillance. Malaria parasitemia will be detected by thick blood smear (TBS), which will be performed every two weeks starting two weeks after the second vaccination (to allow time for the vaccine to work) and extending to week 26 after the second vaccination (24-week surveillance period). Surveillance will continue for 40 weeks but the primary outcome will be determined at 24 weeks of surveillance so the data are comparable to other studies of PfSPZ vaccines.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Healthy males and females, based on clinical and laboratory findings
From the age 18 to 50 years
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
Genetically attenuated PfSPZ Vaccine
Biological/VaccinePfSPZ-LARC2 Vaccine is composed of aseptic, purified, vialed, cryopreserved, genetically altered PfNF54 sporozoites (SPZ).
Normal Saline (0.9% Sodium Chloride)
Other interventionThe placebo control is normal saline solution (0.9% sodium chloride) and is also administered by DVI.
Treatment groups
180 Participants
are divided into 3 treatment groupsGroup A: Group 2 SIngle Dose Vaccine GroupExperimental treatment 2 interventions
Group B: Group 1 Double Dose Vaccine GroupExperimental treatment 1 intervention
Group C: Group 3 PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Vaccine efficacy of PfSPZ-LARC2 Vaccine as compared to normal saline, placebo against first Pf infection as detected by thick blood smear (TBS).
TBS positive for asexual Pf at any parasite density collected every 2 weeks and at any time participants present with symptoms of malaria, starting 2 weeks after last dose of vaccine or placebo and extending 24 additional weeks.
Time frame
2-24 weeks after last dose of vaccine or placeboSecondary outcomes
1
Safety and tolerability of PfSPZ-LARC2 Vaccine - solicited AEs
Incidence of grade 3 solicited adverse events (AEs) in the 14 days post each administration of vaccine or placebo
Time frame
14 days post each administration of vaccine or placebo2
Safety and tolerability of PfSPZ-LARC2 Vaccine- laboratory abnormalities
Incidence of laboratory abnormalities at 1 week post each administration of vaccine or placebo
Time frame
1 week post each administration of vaccine or placebo3
Safety and tolerability of PfSPZ-LARC2 Vaccine- unsolicited AEs
Incidence of related grade 3 unsolicited AEs in the 28 days post each administration of vaccine or placebo
Time frame
28 days post each administration of vaccine or placebo4
Safety and tolerability of PfSPZ-LARC2 Vaccine- SAEs
Incidence of related serious adverse events (SAEs) after the first administration of vaccine or placebo until the end of the study
Time frame
After the first administration of vaccine or placebo until the end of the studySponsors 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
Fred Hutchinson Cancer Center
Collaborator
Source ClinicalTrials.gov