Trial for Malaria Vaccine Candidate, PfPEBS (P. Falciparum Pre-Erythrocytic and Blood Stage)

NCT01605786 | Unknown Phase 1 DMC

• 2 other identifiers: Pf PEBS-Ia-IIa2012-002294-54
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study intends to test the hypothesis that the malaria antigen PfPEBS, manufactured as a synthetic protein and adjuvanted with aluminium hydroxide will be well-tolerated and immunogenic (Phase 1), functionally active against the erythrocytic stages (Phase 1) and efficacious (Phase 2) against the pre-erythrocytic stages in protecting against an artificial malaria challenge using Pf sporozoites in a healthy adult population.

Conditions

Malaria

Keywords

Malaria; Plasmodium falciparum; vaccine; ADCI; sporozoite challenge; pre-erythrocytic; erythrocytic

Outcome Measures

Primary Outcomes (3)

• Adverse events following 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.

  Up to one year following first vaccination

• Change from baseline of antibodies active in the ADCI assay

  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.

  Within one year following first vaccination

• Parasitemia following mosquito 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.

  From Day 4 up to Day 21 post challenge

Secondary Outcomes (3)

• Antibodies against synthetic PEBS

  Within one year following first vaccination

• Antibodies against parasite antigen

  Within one year following first vaccination

• PEBS Interferon-Gamma

  Within one year following first vaccination

Study Arms (3)

PEBS Low dose

EXPERIMENTAL

Biological: Lyophilised PEBS synthetic protein (PfPEBS)

PEBS High dose

EXPERIMENTAL

Biological: Lyophilised PEBS synthetic protein (PfPEBS)

Control

ACTIVE COMPARATOR

Other: Rehydragel™ HPA

Interventions

Lyophilised PEBS synthetic protein (PfPEBS) BIOLOGICAL

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.

PEBS Low dose

Rehydragel™ HPA OTHER

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.

Control

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female age \> 18 and \< 45 years
• Good general health based on history, physical en laboratory examination
• Available for and willingness to undergo a P. falciparum sporozoite infected mosquito challenge following the immunization course
• Resident in or near Lausanne for the duration of the study having 24h access to a mobile telephone
• Willingness to stay in special accommodation (hotel or equivalent) from day 5 up to one day after parasite positivity , or up to day 15 post EHMI
• Agreement to refrain from blood donation during the course of the study and afterwards
• Negative pregnancy test and the use of effective contraception during the whole study period if deemed appropriate
• Willingness to undergo an HIV test and other serologies
• Willingness to allow investigators to notify their general practitioner, if any, of participation in this trial
• Willingness to allow investigators to request medical information, relevant for participation in this trial, from their general practitioner, if any
• Written informed consent following proper understanding of the meaning and procedures of the Phase I and IIa parts of the trial
• Agreement to inform study doctor and to release medical information concerning contra-indications for participation in the study
• Willingness to undergo screening for drugs such as amphetamines, opiates and cocaine

You may not qualify if:

• Any history of malaria
• Known exposure to malaria in the previous 6 months, defined as a visit to a malaria endemic region. For practical purposes, all regions for which malaria chemoprophylaxis is advised by travel clinic are considered malaria endemic
• Planned to travel to endemic malaria areas during the study period
• Prior administration of an investigational malaria vaccine
• Administration of a vaccine or gammaglobulin not foreseen by the clinical trial protocol within 30 days prior to the first immunization and up to six months after the last immunization.
• Participation in any other clinical trial within 90 days prior to the onset of the trial or more than four clinical trials in the past year
• The use of chronic medication (defined as more than 14 days), especially immunosuppressive agents or antibiotics during the study period
• The use of chronic immunosuppressive drugs or other immune modifying drugs within three months of vaccination (inhaled and topical corticosteroids are allowed)
• Positive serological tests for P. falciparum (PEBS) ELISA and/or a positive P. falciparum whole parasite ELISA
• Known hypersensitivity to vaccine components
• History of severe reactions or allergy to mosquito bites
• Contra indications to Malarone® including treatment taken by the volunteers that interfere with Malarone® (e.g. concurrent use of medicines that prolong QT interval)
• History of allergic disease to or reactions likely to be exacerbated by any component of the vaccine
• Any confirmed or suspected immunosuppressive or immunodeficiency condition, including asplenia.
• History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)

Sponsors & Collaborators

• Vac4All: lead
• Centre Hospitalier Universitaire Vaudois: collaborator
• Radboud University Medical Center: collaborator
• European Commission: collaborator

Study Sites (1)

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

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

Study Officials

• Pierre L Druilhe, MD

  Vac4All

  STUDY DIRECTOR

• Francois Spertini, MD

  Centre Hospitalier Universitaire Vaudois (CHUV)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pierre Druilhe, MD

CONTACT

+33142733541; druilhe@vac4all.org

Blaise Genton, MD

CONTACT

+41 21 556 58 68; Blaise.Genton@chuv.ch

Study Design

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

Study Record Dates

• First Submitted: May 18, 2012
• First Posted: May 25, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: August 1, 2013
• Last Updated: May 25, 2012

Record last verified: 2012-05

Locations

CH (1)