Controlled Human Malarial Infection by Intravenous Injection of Plasmodium Falciparum Sporozoites in Non-Immune Adults

This study has been completed.
Sponsor:
Collaborator:
Institute of Tropical Medicine, University of Tuebingen
Information provided by (Responsible Party):
Sanaria Inc.
ClinicalTrials.gov Identifier:
NCT01624961
First received: June 19, 2012
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

The study is designed to establish the best dose to safely infect healthy individuals with Plasmodium falciparum sporozoites (PfSPZ) via intravenous (IV) injection.


Condition Intervention Phase
Malaria
Biological: PfSPZ Challenge
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Controlled Human Malarial Infection by Intravenous Injection of Plasmodium Falciparum Sporozoites in Non-Immune Adults

Resource links provided by NLM:


Further study details as provided by Sanaria Inc.:

Primary Outcome Measures:
  • The infectivity of the administration regimens will be assessed by thick film microscopy and PCR for P. falciparum DNA. [ Time Frame: Day 5 until day 21 or until treatment ] [ Designated as safety issue: No ]
    Parasitology and parasite molecular biology tests: These tests are used to determine malaria parasites (thick blood smear and PCR). Both tests are performed at screening and then approximately every 12 hours during the period of intense observation from day 5 until day 21 or until treatment. Thereafter, these tests are performed during safety follow-ups at Days 28, 84, and 168. Turn over time for thick blood smear microscopy is < 2 hours to ensure timely treatment in case of a positive result. PCR results are available only after study completion.


Secondary Outcome Measures:
  • The time from parasite inoculation to first detection of blood stage parasitemia will be assessed by thick blood film microscopy. [ Time Frame: Day 5 until day 21 or until treatment ] [ Designated as safety issue: No ]
  • The safety of PfSPZ Challenge administered ID or IV and the resultant P. falciparum infection will be assessed by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements [ Time Frame: Screening to Day 168 ] [ Designated as safety issue: Yes ]
    These tests include full blood picture (complete blood count), liver enzymes and creatinine. All of these will be performed once at screening, Day -1 (day before challenge), Day 21 when no parasitemia occurs until then and day of malaria diagnosis. Lastly, these tests will also be performed during safety follow up at Days 28, 84 and 168.


Enrollment: 30
Study Start Date: June 2012
Study Completion Date: February 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 50 PfSPZ IV Biological: PfSPZ Challenge
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
  • PfSPZ Challenge
  • Aseptic, cryopreserved P. falciparum sporozoites
Experimental: 200 PfSPZ IV Biological: PfSPZ Challenge
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
  • PfSPZ Challenge
  • Aseptic, cryopreserved P. falciparum sporozoites
Experimental: 800 PfSPZ IV Biological: PfSPZ Challenge
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
  • PfSPZ Challenge
  • Aseptic, cryopreserved P. falciparum sporozoites
Experimental: 3200 PfSPZ IV Biological: PfSPZ Challenge
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
  • PfSPZ Challenge
  • Aseptic, cryopreserved P. falciparum sporozoites
Experimental: 2500 PfSPZ ID Biological: PfSPZ Challenge
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
  • PfSPZ Challenge
  • Aseptic, cryopreserved P. falciparum sporozoites

Detailed Description:

TÜCHMI-001 is a single center, open label, randomized and controlled human pilot study to optimize controlled human malaria infection(CHMI) administered by PfSPZ Challenge. Volunteers will be inoculated with PfSPZ Challenge. Controls will receive the PfSPZ Challenge by ID administration. The remaining volunteers will receive the PfSPZ Challenge by IV administration. 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 and dose-levels.

Volunteers and clinical investigators will not be blinded to group allocation, however laboratory investigators processing blood films and samples for PCR analysis will be blinded to group allocation.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adults aged 18 to 45 years
  • Able and willing (in the Investigator's opinion) to comply with all study requirements
  • Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner if required
  • Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a low failure rate; i.e. less than 1% per year)
  • Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local blood banking eligibility criteria
  • Written informed consent to undergo CHMI
  • Reachable (24/7) by mobile phone during the whole study period
  • Willingness to take a curative anti-malarial regimen
  • Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required
  • Answer all questions on the informed consent quiz correctly
  • A body mass index <35
  • A haemoglobin concentration ≥12 g/dl for women and ≥14 g/dl for men

Exclusion Criteria:

  • History of P. falciparum malaria
  • History of long term residence (>5 years) in area known to have significant transmission of P. falciparum
  • Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin)
  • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
  • Prior receipt of an investigational malaria vaccine
  • HIV infection
  • Any confirmed or suspected immunosuppressive or immunodeficient state, 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 enrolment
  • Presence 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
  • Contraindications to the use of the first-line anti-malarial medications: Atovaquone/Proguanil, Artemether/Lumefantrine, 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 60g (men) or 40g (women) per day
  • Suspected or known injecting drug abuse in the 5 years preceding enrolment
  • Seropositive for hepatitis B surface antigen (HBsAg)
  • Seropositive for hepatitis C virus (antibodies to HCV)
  • Falling in moderate risk or higher categories for fatal or non-fatal cardiovascular event within 5 years (>10%) determined by non-invasive criteria for cardiac risk
  • Abnormal electrocardiogram on screening: pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, non-sinus rhythm except isolated premature atrial contractions, right of left bundle branch block, advanced A-V heart block (secondary or tertiary)
  • A QT/QTc interval >450 ms
  • 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, in the opinion of the Investigator, 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: NCT01624961

Locations
Germany
Eberhard Karls University of Tübingen, Germany
Tübingen, Germany, D-72074
Sponsors and Collaborators
Sanaria Inc.
Institute of Tropical Medicine, University of Tuebingen
Investigators
Principal Investigator: Benjamin G Mordmüller, MD Eberhard Karls University of Tübingen, Germany
  More Information

No publications provided

Responsible Party: Sanaria Inc.
ClinicalTrials.gov Identifier: NCT01624961     History of Changes
Other Study ID Numbers: TUCHMI-001
Study First Received: June 19, 2012
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanaria Inc.:
Controlled human malaria infection (CHMI)
Malaria challenge
Plasmodium falciparum
PfSPZ Challenge

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on July 23, 2014