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Safety and Protective Efficacy of IV Immunization With Cryopreserved PfSPZ Under A/P Chemoprophylaxis

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Disease Information

Descriptive Information
Brief Title † Safety and Protective Efficacy of IV Immunization With Cryopreserved PfSPZ Under A/P Chemoprophylaxis
Official Title † Safety and Protective Efficacy of Intravenous Immunization With Cryopreserved Plasmodium Falciparum Sporozoites Under Atovaquone/Proguanil Chemoprophylaxis
Brief Summary Single center, randomized, placebo-controlled, double-blinded trial using PfSPZ Challenge (NF54) under A/P chemoprophylaxis for immunization and PfSPZ Challenge (NF54) for repeat CHMI. A total of 30 adult, healthy, malaria naïve volunteers will receive three injections by Direct Venous Inoculation (DVI) of either placebo (n = 10), 51,200 PfSPZ Challenge (NF54) (n = 10), or 150,000 PfSPZ Challenge (NF54) (n = 10) under chemoprophylaxis with A/P at 4 week intervals. The placebo will be NaCl 0.9%. Ten weeks after the last dose of PfSPZ Challenge (NF54) for immunization, volunteers will undergo first CHMI and followed until asexual blood stage parasitemia, detected by quantitative real time PCR (qPCR) or thick blood smear microscopy. If parasitemic, they will be treated with A/P (used in this case as a standard treatment regimen). In the event of no parasitemia, volunteers will be followed until Day 28 post-CHMI and will not receive A/P. Forty-four weeks after the last immunization, a second CHMI will be administered to assess longevity of protection. All volunteers will be followed up to 28 days post-inoculation. Those developing parasitemia will be treated with A/P.
Detailed Description
Study Phase Phase 1
Study Type † Interventional
Study Design †
Primary Outcome Measure † Number or occurrence of related Grade 3 and 4 adverse events (AEs) and serious adverse events (SAEs)
Secondary Outcome Measure † Occurrence of any related AE
Condition † Malaria
Intervention † Drugatovaquone/proguanil 250mg/100mg (A/P)
Study Arms / Comparison Groups 51,200 PfSPZ Three injections of 51,200 PfSPZ Challenge (P. falciparum strain: NF54) under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals 150,000 PfSPZ Three injections of 150,000 PfSPZ Challenge (P. falciparum strain: NF54) under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals Placebo Three injections of NaCl 0,9% solution under chemoprophylaxis with atovaquone/proguanil 250mg/100mg (A/P) at 4 week intervals
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 30
Start Date † November 28, 2016
Completion Date March 2018
Primary Completion Date March 2018
Eligibility Criteria † Inclusion Criteria: - Healthy adults aged 18 to 45 years. - Able and willing (in the Investigator's opinion) to comply with all study requirements. - Willing to allow the investigators to discuss the volunteer's medical history with their general practitioner if required. - Residence in Tübingen or surroundings for the period of the trial. - Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a low failure rate; i.e. less than 1% per year). - Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local and national blood banking eligibility criteria (currently four years in Germany). - Provision of written informed consent to receive PfSPZ Challenge for immunization and subsequently for CHMI. - Reachable (24/7) by mobile phone during the immunization and CHMI period. - Willingness to take A/P during immunization and a curative antimalarial regimen following CHMI. - Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required. - Answer all questions on the informed consent quiz correctly. - A body mass index 18-35. Exclusion Criteria: - History of P.falciparum malaria. - Planned travel to malaria endemic areas during the study period. - Use of systemic antibiotics with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin,erythromycin, fluoroquinolones, or azithromycin). - Receipt of an investigational product in the 90 days preceding enrollment, or planned receipt during the study period. - HIV infection. - Any confirmed or suspected immunosuppressive or immunodeficient state (e.g. repeated and/or unusual infections),history of infection caused by opportunistic organisms any infection or combination of infections that suggest underlying immunodeficiency, history of meningitis, encephalitis, septic shock, life-threatening soft tissue infection, more than one pneumonia, asplenia and/or chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)). - Use of immunoglobulins or blood products within 3 months prior to enrolment. - Known (or signs consistent with) sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait, glucose-6-phosphate dehydrogenase deficiency. - Pregnancy, lactation or intention to become pregnant during the study. - Contraindications to the use of the following antimalarial medications: A/P, artemether-lumefantrine - History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). - History of serious psychiatric condition that may affect participation in the study - Any other serious chronic illness requiring hospital specialist supervision. - Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 60 g (men) or 40 g (women) per day or a carbohydrate deficient transferrin (CDT) level ≥2.5%. - Suspected or known injected drug abuse in the 5 years preceding enrollment. - Positive for hepatitis B surface antigen (HBs-antigen). - Seropositive for hepatitis C virus (antibodies to HCV). - Falling in moderate risk or higher categories for fatal or non-fatal cardiovascular event within 5 years (>10%) determined by non-invasive criteria for cardiac risk 84. - Abnormal electrocardiogram on screening: pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, clinically significant arrythmias, left bundle branch block, secondary or tertiary AV block - A QT/QTcB interval >450 ms. - Volunteers unable to be closely followed for social, geographic or psychological reasons. - CrCL
Gender All
Ages 18 Years - 45 Years
Accepts Healthy Volunteers Accepts Healthy Volunteers
Contacts ††
Location Countries †
Administrative Information
NCT ID † NCT02858817
Organization ID MALACHITE
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † University Hospital Tuebingen
Collaborators †† Sanaria Inc.
Investigators † Principal Investigator: Peter G Kremsner, Prof, University Hospital Tübingen, Tübingen, Germany
Information Provided By
Verification Date July 2016
First Received Date † July 28, 2016
Last Updated Date March 29, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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