- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01624961
Controlled Human Malarial Infection by Intravenous Injection of Plasmodium Falciparum Sporozoites in Non-Immune Adults
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Tübingen, Germany, D-72074
- Eberhard Karls University of Tübingen, Germany
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 50 PfSPZ IV
PfSPZ Challenge
|
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
|
Experimental: 200 PfSPZ IV
PfSPZ Challenge
|
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
|
Experimental: 800 PfSPZ IV
PfSPZ Challenge
|
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
|
Experimental: 3200 PfSPZ IV
PfSPZ Challenge
|
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
|
Experimental: 2500 PfSPZ ID
PfSPZ Challenge
|
PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
|
Day 5 until day 21 or until treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Day 5 until day 21 or until treatment
|
|
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
|
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.
|
Screening to Day 168
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Benjamin G Mordmüller, MD, Eberhard Karls University of Tübingen, Germany
Publications and helpful links
General Publications
- Gomez-Perez GP, Legarda A, Munoz J, Sim BK, Ballester MR, Dobano C, Moncunill G, Campo JJ, Cistero P, Jimenez A, Barrios D, Mordmuller B, Pardos J, Navarro M, Zita CJ, Nhamuave CA, Garcia-Basteiro AL, Sanz A, Aldea M, Manoj A, Gunasekera A, Billingsley PF, Aponte JJ, James ER, Guinovart C, Antonijoan RM, Kremsner PG, Hoffman SL, Alonso PL. Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naive volunteers: effect of injection volume and dose on infectivity rates. Malar J. 2015 Aug 7;14:306. doi: 10.1186/s12936-015-0817-x.
- Mordmuller B, Supan C, Sim KL, Gomez-Perez GP, Ospina Salazar CL, Held J, Bolte S, Esen M, Tschan S, Joanny F, Lamsfus Calle C, Lohr SJ, Lalremruata A, Gunasekera A, James ER, Billingsley PF, Richman A, Chakravarty S, Legarda A, Munoz J, Antonijoan RM, Ballester MR, Hoffman SL, Alonso PL, Kremsner PG. Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection: a dose-finding trial in two centres. Malar J. 2015 Mar 18;14:117. doi: 10.1186/s12936-015-0628-0.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TUCHMI-001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
Clinical Trials on PfSPZ Challenge
-
National Institute of Allergy and Infectious Diseases...CompletedPlasmodium Falciparum InfectionUnited States
-
Sanaria Inc.Barcelona Centre for International Health ResearchCompleted
-
Sanaria Inc.German Federal Ministry of Education and Research; German Center for Infection... and other collaboratorsCompleted
-
London School of Hygiene and Tropical MedicineRadboud University Medical Center; Sanaria Inc.Completed
-
Sanaria Inc.Swiss Tropical & Public Health Institute; Ifakara Health Institute; Government... and other collaboratorsCompleted
-
Sanaria Inc.Swiss Tropical & Public Health Institute; Ifakara Health Institute; Medical Care... and other collaboratorsCompleted
-
Sanaria Inc.Fred Hutchinson Cancer CenterCompleted
-
Sanaria Inc.Swiss Tropical & Public Health Institute; Ifakara Health Research and Development...Completed
-
Sanaria Inc.Swiss Tropical & Public Health Institute; Ifakara Health Institute; Government... and other collaboratorsCompleted
-
Sanaria Inc.Swiss Tropical & Public Health Institute; Ifakara Health Institute; Medical Care...CompletedMalaria | Malaria,FalciparumTanzania