Clinical trial NCT01465048: Optimisation of Controlled Human Malaria Infection Using Sporozoites Administered by Needle and Syringe
Official title: A Pilot Study to Optimise Controlled Human Malaria Infections Using Plasmodium Falciparum Sporozoites Administered by Needle and Syringe
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Plasmodium Falciparum
Keywords: Malaria
Protozoan Infections
Parasitic Diseases
Malaria Challenge
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Sanaria Inc.
First posted: 2011-11-04
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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.

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.
* 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.

Primary outcomes:
measure: Number of Participants Infected
timeFrame: 21 days post administration of PfSPZ Challenge
Secondary outcomes:
measure: Frequency, Incidence and Nature of Adverse Events and Serious Adverse Events Arising.
timeFrame: Participants will be followed for the duration of the study, an expected average of 3 months
measure: Dynamics of Plasmodium Falciparum Parasite Growth Following PfSPZ Challenge Administered in Various Regimens
timeFrame: 21 days post administration of PfSPZ Challenge
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Study officials:
affiliation: University of Oxford
name: Adrian VS Hill, DPhil FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Longley RJ, Halbroth BR, Salman AM, Ewer KJ, Hodgson SH, Janse CJ, Khan SM, Hill AVS, Spencer AJ. Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine. Infect Immun. 2017 Feb 23;85(3):e00641-16. doi: 10.1128/IAI.00641-16. Print 2017 Mar.
citation: Hodgson SH, Llewellyn D, Silk SE, Milne KH, Elias SC, Miura K, Kamuyu G, Juma EA, Magiri C, Muia A, Jin J, Spencer AJ, Longley RJ, Mercier T, Decosterd L, Long CA, Osier FH, Hoffman SL, Ogutu B, Hill AV, Marsh K, Draper SJ. Changes in Serological Immunology Measures in UK and Kenyan Adults Post-controlled Human Malaria Infection. Front Microbiol. 2016 Oct 13;7:1604. doi: 10.3389/fmicb.2016.01604. eCollection 2016.
citation: Sheehy SH, Spencer AJ, Douglas AD, Sim BK, Longley RJ, Edwards NJ, Poulton ID, Kimani D, Williams AR, Anagnostou NA, Roberts R, Kerridge S, Voysey M, James ER, Billingsley PF, Gunasekera A, Lawrie AM, Hoffman SL, Hill AV. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe. PLoS One. 2013 Jun 18;8(6):e65960. doi: 10.1371/journal.pone.0065960. Print 2013.