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PfSPZ Challenge With Prophylaxis in Mali

2016-12-19 20:38:22 | BioPortfolio

Summary

Single site, double-blinded, randomized, placebo-controlled clinical trial of PfSPZ-CVac safety, tolerability, immunogenicity and efficacy against naturally occurring malaria in malaria-exposed Malian adults. The overall goal of the study is to evaluate if a regimen of PfSPZ-CVac (PfSPZ Challenge under chemoprophylaxis) is safe, well-tolerated, and provides sterile protection against naturally-occurring malaria in malaria-experienced adults. The study population includes 62 healthy, malaria-experienced adults aged 18-45 years, inclusive, residing in Bougoula Hameau and surrounding villages, Mali.

Description

The proposed study is a single site, double-blinded, randomized, placebo-controlled clinical trial of PfSPZ-CVac safety, tolerability, immunogenicity and efficacy against naturally occurring malaria in malaria-exposed Malian adults. The overall goal of the study is to evaluate if a regimen of PfSPZ-CVac (PfSPZ Challenge under chemoprophylaxis) is safe, well-tolerated, and provides sterile protection against naturally-occurring malaria in malaria-experienced adults. Participants will receive three immunizing PfSPZ Challenge injections via direct venous inoculation (DVI) four weeks apart under chloroquine chemoprophylaxis. The PfSPZ Challenge dose will be 204,800 PfSPZ. This is based on results of studies in Europe and in Africa. In Tübingen, Germany, 100% of malaria-naïve adults who received three doses of 51,200 PfSPZ every four weeks under chloroquine chemoprophylaxis were protected against homologous controlled human malaria infection (CHMI). At the same time, studies of PfSPZ Vaccine in malaria-experienced adults in Mali and in Tanzania demonstrate that higher doses of PfSPZ are required to demonstrate immunogenicity and high grade protection in malaria-experienced adults that is comparable to that achieved in malaria-naïve adults studied in the USA. For this reason, the dose selected for this study is four-fold higher than the dose used for Tübingen, Germany. Controls will receive 0.9% sodium chloride (NaCl) as placebo. All participants will receive a standard chemoprophylactic regimen of chloroquine (CQ) for 10 weeks. Chloroquine will be given as a loading dose (600mg chloroquine base) two days before the first administration of PfSPZ Challenge, followed by weekly doses of chloroquine (300mg chloroquine base weekly). Participants will also be treated with a 7-day regimen of artesunate (200 mg per day) after the last PfSPZ Challenge dose of 204,800 sporozoites for malaria parasite clearance, one week after the last CQ dose is given.

A total of 62 participants will be randomized in a 1:1 ratio to one of two groups and will be inoculated with PfSPZ Challenge or 0.9% NaCl by DVI so that a total of 62 adults will participate in the study. Participants will be recruited from the MRTC's Bougoula-Hameau site. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected. Volunteers, clinical and laboratory investigators will be blinded to group allocation. Participants will be followed every four weeks after the last vaccination as outpatients for active malaria diagnosis and treatment. Passive follow-up will be accomplished by continuous availability of study staff onsite to diagnose and treat malaria and other medical issues that arise.

The primary objective of this study is to assess the safety and tolerability of PfSPZ Challenge compared to placebo among malaria-experienced adults taking chloroquine prophylaxis (PfSPZ-CVac). The secondary objectives are: 1. to assess the protective efficacy of PfSPZ-CVac against naturally transmitted P. falciparum malaria infection as diagnosed by thick blood smear microscopy, 2. To assess protective efficacy of PfSPZ-CVac against naturally transmitted P. falciparum malaria infection as diagnosed by qPCR, 3. to assess the expanded efficacy of PfSPZ-CVac compared to placebo, and 4. to examine the immune response to P. falciparum malaria infection.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Conditions

Plasmodium Falciparum Infection

Intervention

Artesunate, Chloroquine, PfSPZ (NF54), Placebo

Location

University of Bamako - Epidemiology of Parasitic Diseases - Malaria Research and Training Center
Sikasso
Mali

Status

Not yet recruiting

Source

National Institute of Allergy and Infectious Diseases (NIAID)

Results (where available)

View Results

Links

Published on BioPortfolio: 2016-12-19T20:38:22-0500

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Medical and Biotech [MESH] Definitions

A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are PLASMODIUM FALCIPARUM; PLASMODIUM MALARIAE; PLASMODIUM OVALE, and PLASMODIUM VIVAX. Species causing infection in vertebrates other than man include: PLASMODIUM BERGHEI; PLASMODIUM CHABAUDI; P. vinckei, and PLASMODIUM YOELII in rodents; P. brasilianum, PLASMODIUM CYNOMOLGI; and PLASMODIUM KNOWLESI in monkeys; and PLASMODIUM GALLINACEUM in chickens.

A surface protein found on Plasmodium species which induces a T-cell response. The antigen is polymorphic, sharing amino acid sequence homology among PLASMODIUM FALCIPARUM; PLASMODIUM CHABAUDI; PLASMODIUM VIVAX; and PLASMODIUM YOELII.

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A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.

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