Topics

Effect of Plasmodium Falciparum Exposure and Sickle Cell Trait on Infection Rates and Kinetics After IV Administration of PfSPZ Challenge

2014-09-29 15:57:12 | BioPortfolio

Summary

The study is designed to establish infectivity of Plasmodium falciparum sporozoites (PfSPZ) via intravenous (IV) administration in three groups with different malaria immunity-status:

1. Adults with a history of lifelong malaria exposure without sickle cell trait

2. Adults with a history of lifelong malaria exposure with sickle cell trait

3. Adults without previous malaria episodes without sickle cell trait

Initially a dose of 3,200 PfSPZ will be given and the time until thick blood smear positivity after challenge will be assessed. If in any of the groups with a history of lifelong malaria exposure, 50% or less of individuals become thick blood smear positive during the 28 days post injection of PfSPZ Challenge, the dose will be increased 4-fold to 12,800 PfSPZ in this group.

Description

LACHMI-001 is a partially-blinded, human pilot trial to study immunity against P. falciparum malaria in a controlled infection setting. The main objective is to characterise the role of sickle cell trait and naturally acquired immunity in development of malaria, defined by positive smear for P. falciparum and signs or symptoms associated with malaria. Three groups of volunteers will receive radical cure treatment and subsequently PfSPZ Challenge by IV administration. The groups are:

1. Adults with naturally acquired immunity and HbAA (Group IA, n=10-20)

2. Adults with naturally acquired immunity and HbAS (Group IS, n=10-20)

3. Adults without previous exposure to malaria and HbAA (Group NI, n=5)

The initial challenge dose of 3,200 PfSPZ administered once intravenously leads to consistent infection in naïve adults (15/15 in prior studies) and thus should infect all volunteers in Group 3. However, volunteers with naturally acquired immunity or sickle cell trait might require a higher dose. Thus if 50% or less of volunteers become parasitemic in Groups IA or IS, 10 additional volunteers will be enrolled and challenged with 12,800 PfSPZ. All volunteers will be healthy adults aged 18 to 30 years. Safety and infectivity data will be collected for each of the regimens and dose-levels. Effective treatment is initiated immediately upon development of parasitemia together with the presence of symptoms associated with malaria.

Laboratory staff reading blood films and processing samples will be blinded to group allocation. Volunteers and clinical investigators will be blinded to group allocation among the IA and IS groups.

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Conditions

Plasmodium Falciparum Malaria

Intervention

PfSPZ Challenge, clindamycin

Location

Centre de Recherches Médicales de Lambaréné
Lambaréné
Gabon
BP 118

Status

Recruiting

Source

Sanaria Inc.

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-09-29T15:57:12-0400

Clinical Trials [849 Associated Clinical Trials listed on BioPortfolio]

Clinical Trial of the PfSPZ Vaccine

The purpose of this study is to determine the safety and tolerability of a non-replicating, metabolically active Plasmodium falciparum sporozoite (PfSPZ) vaccine in malaria-naïve healthy ...

PfSPZ Challenge in Non-immune Adults in Baltimore, USA

This is a single center, randomized and controlled human study to optimize controlled human malaria infection (CHMI) administered by direct venous inoculation (DVI). 36 healthy adults aged...

PfSPZ Challenge With Prophylaxis in Mali

Single site, double-blinded, randomized, placebo-controlled clinical trial of PfSPZ-CVac safety, tolerability, immunogenicity and efficacy against naturally occurring malaria in malaria-ex...

A Study to Determine if New Types of Malaria Vaccines Are Safe, Effective and Lead to Immunity in Kenyan Adults

This is a phase IIb clinical trial in malaria-exposed individuals to assess the immunogenicity, safety and efficacy of the two vaccines in the context of controlled human malaria infection...

PfSPZ Challenge in Healthy Malaria-Naïve Adults in the United States

This phase 1, double-blinded, randomized, placebo-controlled study will enroll 36 healthy volunteers to receive 1 of 3 regimens of PfSPZ or placebo, randomized 3:1. They will also receive ...

PubMed Articles [3849 Associated PubMed Articles listed on BioPortfolio]

Severity of Plasmodium falciparum and non-falciparum malaria in travelers and migrants: a nationwide observational study over two decades in Sweden.

The aim was to assess factors affecting disease severity in imported P. falciparum and non-falciparum malaria.

Plasmodium vivax relapse rates following falciparum malaria reflect previous transmission intensity.

Between 2003 and 2010, 687 (23.8%) of 2885 patients treated for falciparum malaria in clinical studies in Myanmar or on the Thailand-Myanmar border had recurrent Plasmodium vivax malaria within 63 day...

Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria.

The World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum (P falciparum) malaria. Concerns about artemisinin resistance...

Plasmodium knowlesi malaria in Sabah, Malaysia, 2015-2017: ongoing increase in incidence despite near-elimination of the human-only Plasmodium species.

Malaysia aims to eliminate malaria by 2020. However, while cases of Plasmodium falciparum and P. vivax have fallen substantially, the incidence of zoonotic malaria from P. knowlesi continues to increa...

Identifying the components of acidosis in patients with severe P. falciparum malaria using metabolomics.

Acidosis in severe Plasmodium falciparum malaria is associated with high mortality yet the pathogenesis remains incompletely understood. The aim of this study was to determine the nature and source of...

Medical and Biotech [MESH] Definitions

A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.

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.

Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.

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.

Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.

More From BioPortfolio on "Effect of Plasmodium Falciparum Exposure and Sickle Cell Trait on Infection Rates and Kinetics After IV Administration of PfSPZ Challenge"

Quick Search

Relevant Topics

Malaria
Malaria is a serious tropical disease spread by mosquitoes. If malaria is not diagnosed and treated promptly, it can be fatal. What causes malaria? Malaria is caused by a type of parasite known as Plasmodium. There are many different types of Plasmod...

Immunology
Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...


Searches Linking to this Trial