Malaria, Plasmodium Falciparum
Conditions
Keywords
Malaria, Protozoan Infections, Parasitic Diseases, Malaria Challenge
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.
Interventions
BIOLOGICALPlasmodium falciparum sporozoites 2sites
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intradermal injection sites
BIOLOGICALPlasmodium falciparum sporozoites 1 site
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intramuscular injection sites
BIOLOGICALPlasmodium falciparum sporozoites 1site
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 25,000 sporozoites, 50ulx2, 2 intramuscular injection sites
Sponsors
Sanaria Inc.
University of Oxford
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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. * Contraindications to the use of all three proposed anti-malarial medications; Malarone, Riamet and Chloroquine. * 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 42 units every week. * Suspected or known injecting drug abuse in the 5 years preceding enrollment. * Seropositive for hepatitis B surface antigen (HBsAg). * Seropositive for hepatitis C virus (antibodies to HCV). * An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.39 * Positive family history in 1st and 2nd degree relatives \< 50 years old for cardiac disease. * Volunteers unable to be closely followed for social, geographic or psychological reasons. * Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. * Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Infected | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | To assess the safety of PfSPZ Challenge administered in various regimens by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements, including lab reports and adverse events. |
| Dynamics of Plasmodium Falciparum Parasite Growth Following PfSPZ Challenge Administered in Various Regimens | 21 days post administration of PfSPZ Challenge | To determine the parasite growth dynamics of PfSPZ Challenge administered in various regimens using highly sensitive PCR for Plasmodium falciparum DNA. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PfSPZ Challenge 2,500 ID | 6 |
| PfSPZ Challenge 2,500 IM | 6 |
| PfSPZ Challenge 25,000 IM | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | Total | PfSPZ Challenge 2,500 ID | PfSPZ Challenge 2,500 IM | PfSPZ Challenge 25,000 IM |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 6 Participants | 6 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 18 participants | 6 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 8 Participants | 3 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 3 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 2 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants Infected
To determine the infectivity rates of PfSPZ Challenge administered in various regimens by thick film microscopy and highly sensitive PCR for Plasmodium falciparum DNA.
Time frame: 21 days post administration of PfSPZ Challenge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PfSPZ Challenge 2,500 ID | Number of Participants Infected | 5 Participants |
| PfSPZ Challenge 2,500 IM | Number of Participants Infected | 3 Participants |
| PfSPZ Challenge 25,000 IM | Number of Participants Infected | 6 Participants |
Secondary
Dynamics of Plasmodium Falciparum Parasite Growth Following PfSPZ Challenge Administered in Various Regimens
To determine the parasite growth dynamics of PfSPZ Challenge administered in various regimens using highly sensitive PCR for Plasmodium falciparum DNA.
Time frame: 21 days post administration of PfSPZ Challenge
Secondary
Frequency, Incidence and Nature of Adverse Events and Serious Adverse Events Arising.
To assess the safety of PfSPZ Challenge administered in various regimens by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements, including lab reports and adverse events.
Time frame: Participants will be followed for the duration of the study, an expected average of 3 months