Trial for Malaria Vaccine Candidate, PfPEBS (P. Falciparum Pre-Erythrocytic and Blood Stage) (PEBS-POC1)
|ClinicalTrials.gov Identifier: NCT01605786|
Recruitment Status : Unknown
Verified May 2012 by Vac4All.
Recruitment status was: Recruiting
First Posted : May 25, 2012
Last Update Posted : May 25, 2012
|Condition or disease||Intervention/treatment||Phase|
|Malaria||Biological: Lyophilised PEBS synthetic protein (PfPEBS) Other: Rehydragel™ HPA||Phase 1 Phase 2|
The study will enroll 36 healthy adult subjects (18-45 years) and randomize them in a double-blind manner into 3 arms of 12 subjects each; 2 of the arms will receive either 5μg or 30μg, both adjuvanted with aluminium hydroxide, given as a 2-dose schedule with a 28 day interval. The third arm of 12 subjects will act as controls, and they will receive aluminium hydroxide only injections.
If the safety and immunogenicity results permit, the subjects will be challenged with live mosquito challenge delivering P falciparum sporozoites to assess pre-erythrocytic vaccine efficacy.
The PfPEBS molecule has been found to have in vivo and in vitro functional activity against the two stages that are clinically significant for malaria namely the pre-erythrocytic stages (sporozoite and liver stages) and the erythrocytic stages.
The formulation is a simple combination of a synthetic protein of 131 amino acids adjuvanted with aluminum hydroxide, the adjuvant with the widest safety records.
The combined Phase 1/2a study is designed in order to achieve 3 co-primary objectives
- Phase 1: To demonstrate safety and tolerability
- Phase 1: To measure the activity against the asexual blood stage of the parasite which is only indirectly estimated by the functional activity of elicited antibodies in ADCI under in-vitro conditions
- Phase 2: To demonstrate efficacy against liver stages by measuring the proportion of subject that are protected following a live sporozoite challenge.
The mechanisms of defenses differ for "liver stages" and "erythrocytic stages". Defenses against "liver stages" are strongly related to the secretion of interferon γ by CD4+Th1 cells, whereas for blood stages the defences depend on antibodies.
Preliminary studies have demonstrated that low antigen doses such as 5 or 2μg produce strong CD4+Th1- interferon γ secreting cells with low antibody titers, whereas higher antigen doses such as 30 or 50μg induce lower CD4 Th1 cell response and markedly higher antibody responses.
Therefore the choice of the two dose ranges for the Pf-PEBS clinical trial protocol is aimed at testing the two main efficacy objectives, one against "liver stages" with a low dose, the other against "the blood stages" with the higher dose.
The Sponsor for the two Phases is Vac4all. The funder for the Phase Ia is the EMVDA programme of the European Commission. The funder for the Phase IIa is Vac4all
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Phase I and IIa Trial for Assessment of Safety, Immunogenicity (Phase Ia) and Efficacy (Phase IIa) Against Sporozoite Challenge of P. Falciparum Pre-Erythrocytic and Blood Stage (PfPEBS-LSP) Malaria Vaccine Candidate|
|Study Start Date :||May 2012|
|Estimated Primary Completion Date :||May 2013|
|Estimated Study Completion Date :||August 2013|
|Experimental: PEBS Low dose||
Biological: Lyophilised PEBS synthetic protein (PfPEBS)
PfPEBS, is a synthetic polypeptide corresponding to amino acids 3112 to 3244 (131 aa) from the Pf 11.1 antigen in 3D7 parasite sequence. It is presented as lyophilised product in multi-dose vials (containing 105 μg for 3 doses of 30 μg ), looking like amorphous white powder. The vaccine is produced by SYNPROSIS in France.
The 5μg dose vaccine will be formulated extemporaneously in aluminium hydroxide adjuvant and given as a 2-dose schedule with a 28 day interval.
|Experimental: PEBS High dose||
Biological: Lyophilised PEBS synthetic protein (PfPEBS)
PfPEBS-LSP, is a synthetic polypeptide corresponding to amino acids 3112 to 3244 (131aa) from the Pf 11.1 antigen in 3D7 parasite sequence. It is presented as lyophilised product in multi-dose vials (containing 105 μg for 3 doses of 30 μg ), looking like amorphous white powder. The vaccine is produced by SYNPROSIS in France.
The 30 μg dose vaccine will be formulated extemporaneously in aluminium hydroxide adjuvant and given as a 2-dose schedule with a 28 day interval.
|Active Comparator: Control||
Other: Rehydragel™ HPA
Aluminium hydroxide adjuvant is being used as the adjuvant for the vaccine and will be used as the comparator in the control group. Vac4all is using Rehydragel™ (Manufacturer Reheis Inc.) which is a highly active protein adsorbent specially compounded for use as a fluid adjuvant. It has low oxide content and is carefully controlled for Al2O3 content and protein binding capacity. It has a lower viscosity than competing adjuvants, which makes it easier to process and handle.
Subjects in the control group will be administered a 0.5 ml injection in a 2-dose schedule at 28 days interval. Each injection will contain approximately 600 µg of Al(OH)3 per injected dose corresponding to 200 µg equivalent of Al3+, similar to the amount being administered in the vaccine group.
- Adverse events following vaccination [ Time Frame: Up to one year following first vaccination ]The safety and reactogenicity of the vaccine will be assessed by comparing the proportion and severity of expected and unexpected adverse events as well as serious adverse events (SAE) between groups.
- Change from baseline of antibodies active in the ADCI assay [ Time Frame: Within one year following first vaccination ]The vaccine antigen should induce adequate antibodies that are active in the ADCI assay, which measures parasite killing of erythrocytic stages of the malaria parasite by antibodies in Monocyte-dependant manner and is hypothesized to be able to provide protection against clinical malaria disease.
- Parasitemia following mosquito challenge [ Time Frame: From Day 4 up to Day 21 post challenge ]Subjects will be monitored for emergence of malaria parasites in the blood, using the gold standard of thick film slide microscopy, and rapid diagnostic testing, RT-PCR and LAMP. Treatment will be initiated as soon as subjects are parasitemic, defined as >1 parasites per 400 fields in a thick blood film, OR a positive RDT OR two positive RT-PCR OR one positive result with RT-PCR AND one positive result with LAMP OR two positive results with two different methods.
- Antibodies against synthetic PEBS [ Time Frame: Within one year following first vaccination ]This will be measured by ELISA
- Antibodies against parasite antigen [ Time Frame: Within one year following first vaccination ]This will be measured by the following methods: whole parasite extract, ELISA, Western Blot, IFAT
- PEBS Interferon-Gamma [ Time Frame: Within one year following first vaccination ]This will be measured by ELISPOT
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01605786
|Contact: Pierre Druilhe, MDfirstname.lastname@example.org|
|Contact: Blaise Genton, MD||+41 21 556 58 68||Blaise.Genton@chuv.ch|
|Centre Hospitalier Universitaire Vaudois (CHUV)||Recruiting|
|Lausanne, Vaud, Switzerland, 1011|
|Sub-Investigator: Blaise Genton, MD|
|Sub-Investigator: Reza Chakour, MD|
|Sub-Investigator: Voumard Rachel, MD|
|Sub-Investigator: Valerie D'Acremont, MD|
|Sub-Investigator: Regine Audran, Phd|
|Sub-Investigator: Robert Sauerwein, MD|
|Sub-Investigator: Ing GJ van Gemert, Phd|
|Study Director:||Pierre L Druilhe, MD||Vac4All|
|Principal Investigator:||Francois Spertini, MD||Centre Hospitalier Universitaire Vaudois (CHUV)|