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

This study has been completed.
Sponsor:
Collaborator:
Sanaria Inc.
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01465048
First received: October 27, 2011
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention
Malaria
Plasmodium Falciparum
Biological: Plasmodium falciparum sporozoites 2sites
Biological: Plasmodium falciparum sporozoites 1 site
Biological: Plasmodium falciparum sporozoites 1site

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Pilot Study to Optimise Controlled Human Malaria Infections Using Plasmodium Falciparum Sporozoites Administered by Needle and Syringe

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Number of Participants Infected [ Time Frame: 21 days post administration of PfSPZ Challenge ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Frequency, Incidence and Nature of Adverse Events and Serious Adverse Events Arising. [ Time Frame: Participants will be followed for the duration of the study, an expected average of 3 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 21 days post administration of PfSPZ Challenge ] [ Designated as safety issue: No ]
    To determine the parasite growth dynamics of PfSPZ Challenge administered in various regimens using highly sensitive PCR for Plasmodium falciparum DNA.


Enrollment: 18
Study Start Date: October 2011
Study Completion Date: February 2013
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Plasmodium falciparum sporozoites 2sites
2,500 sporozoites intradermally
Biological: Plasmodium falciparum sporozoites 2sites
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intradermal injection sites
Experimental: Plasmodium falciparum sporozoites 1 site
2,500 sporozoites intramuscularly
Biological: Plasmodium falciparum sporozoites 1 site
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intramuscular injection sites
Experimental: Plasmodium falciparum sporozoites 1site
25,000 sporozoites intramuscularly
Biological: Plasmodium falciparum sporozoites 1site
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 25,000 sporozoites, 50ulx2, 2 intramuscular injection sites

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01465048

Locations
United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Sanaria Inc.
Investigators
Principal Investigator: Adrian VS Hill, DPhil FRCP University of Oxford
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01465048     History of Changes
Other Study ID Numbers: VAC049
Study First Received: October 27, 2011
Results First Received: April 8, 2013
Last Updated: June 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Oxford:
Malaria
Protozoan Infections
Parasitic Diseases
Malaria Challenge

Additional relevant MeSH terms:
Infection
Malaria
Parasitic Diseases
Protozoan Infections

ClinicalTrials.gov processed this record on October 20, 2014