Optimisation of Controlled Human Malaria Infection Using Sporozoites Administered by Needle and Syringe

Malaria Clinical Trial

Official title:

A Pilot Study to Optimise Controlled Human Malaria Infections Using Plasmodium Falciparum Sporozoites Administered by Needle and Syringe

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01465048
• Other study ID #: VAC049
• Status: Completed
• Phase: N/A
• First received: October 27, 2011
• Last updated: June 18, 2013
• Start date: October 2011
• Est. completion date: February 2013

Study information

• Verified date: June 2013
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 2013
• Est. primary completion date: February 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Malaria
• Plasmodium Falciparum

Intervention

Biological:
• Plasmodium falciparum sporozoites 2sites
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intradermal injection sites
• Plasmodium falciparum sporozoites 1 site
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intramuscular injection sites
• Plasmodium falciparum sporozoites 1site
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 25,000 sporozoites, 50ulx2, 2 intramuscular injection sites

Locations

Country	Name	City	State
United Kingdom	Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital	Oxford

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	Sanaria Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	21 days post administration of PfSPZ Challenge	No
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.	Participants will be followed for the duration of the study, an expected average of 3 months	Yes
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.	21 days post administration of PfSPZ Challenge	No