A Pilot Study to Optimise Controlled Human Malaria Infections Using Plasmodium Falciparum Sporozoites Administered by Needle and Syringe
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Malaria
- Sponsor
- University of Oxford
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Number of Participants Infected
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This is an open label, human pilot study to optimise controlled human malaria infection (CHMI) administered by Plasmodium falciparum sporozoites (PfSPZ. Volunteers will be inoculated with PfSPZ Challenge. The route of administration and dose will vary in order to identify the optimal regimen that achieves the greatest infection rate in volunteers with Plasmodium falciparum. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected for each of the regimens.
Detailed Description
Studies involving CHMI are a powerful tool for investigating malaria vaccine and prophylactic drug efficacy.CHMI has now become established as a key tool to assess the efficacy of novel malaria vaccines and drugs. As CHMI trials are carried out in a controlled environment, they allow unprecedented detailed evaluation of parasite growth and immunological responses, providing essential information for vaccine and drug development. Out of three currently available methods of performing experimental human malaria infections (blood stage infection, mosquito bites and sporozoite infection), experimental injection directly by needle and syringe using aseptic, purified, cryopreserved sporozoites is, in principle, the most accurate and practical way of dosing sporozoites for challenge studies. Recently, Sanaria Inc have been able to overcome the technical issues associated with the production of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. As a result, an Investigational New Drug application (IND) was submitted to the U.S. Food and Drug Administration in February 2009, and a Phase 1 clinical trial with experimental challenge of volunteers was initiated in April 2009. Another trial sponsored by Sanaria to find the dose of aseptic, purified, cryopreserved sporozoites that should be used for experimental human malaria infections is currently ongoing with collaboration with the Radboud University Nijmegen Medical Center, The Netherlands. This trial will be the first time aseptic, purified, cryopreserved P. falciparum sporozoites have been administered intramuscularly to humans.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Women only: Must practice continuous effective contraception for the duration of the study.
- •Agreement to refrain from blood donation during the course of the study and for at least 3 years after the end of their involvement in the study.
- •Written informed consent to undergo CHMI.
- •Reachable (24/7) by mobile phone during the whole study period.
- •Willingness to take a curative anti-malaria regimen.
- •For volunteers not living in Oxford: agreement to stay in a hotel room close to the trial centre during a part of the study (At least Day 6.5 post inoculation until 2 days after treatment commenced).
- •Answer all questions on the informed consent quiz correctly.
Exclusion Criteria
- •History of clinical P. falciparum malaria.
- •Travel to a malaria endemic region during the study period or within the preceding six months with positive P. falciparum serology at screening.
- •Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
- •Receipt of an investigational product in the 30 days preceding enrollment, or planned receipt during the study period.
- •Prior receipt of an investigational malaria vaccine.
- •Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and 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 enrollment.
- •History of sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait.
- •Pregnancy, lactation or intention to become pregnant during the study
- •A history of allergic disease or reactions likely to be exacerbated by malaria infection.
Outcomes
Primary Outcomes
Number of Participants Infected
Time Frame: 21 days post administration of PfSPZ Challenge
To determine the infectivity rates of PfSPZ Challenge administered in various regimens by thick film microscopy and highly sensitive PCR for Plasmodium falciparum DNA.
Secondary Outcomes
- Frequency, Incidence and Nature of Adverse Events and Serious Adverse Events Arising.(Participants will be followed for the duration of the study, an expected average of 3 months)
- Dynamics of Plasmodium Falciparum Parasite Growth Following PfSPZ Challenge Administered in Various Regimens(21 days post administration of PfSPZ Challenge)