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

NCT ID: NCT01624961

Last Updated: 2016-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2013-02-28

Brief Summary

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

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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

50 PfSPZ IV

PfSPZ Challenge

Group Type: EXPERIMENTAL

PfSPZ Challenge

Intervention Type: BIOLOGICAL

PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.

200 PfSPZ IV

PfSPZ Challenge

Group Type: EXPERIMENTAL

PfSPZ Challenge

Intervention Type: BIOLOGICAL

PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.

800 PfSPZ IV

PfSPZ Challenge

Group Type: EXPERIMENTAL

PfSPZ Challenge

Intervention Type: BIOLOGICAL

PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.

3200 PfSPZ IV

PfSPZ Challenge

Group Type: EXPERIMENTAL

PfSPZ Challenge

Intervention Type: BIOLOGICAL

PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.

2500 PfSPZ ID

PfSPZ Challenge

Group Type: EXPERIMENTAL

PfSPZ Challenge

Intervention Type: BIOLOGICAL

PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.

Interventions

PfSPZ Challenge

PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.

Intervention Type: BIOLOGICAL

Other Intervention Names

Aseptic, cryopreserved P. falciparum sporozoites

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institute of Tropical Medicine, University of Tuebingen

OTHER

Sponsor Role: collaborator

Sanaria Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benjamin G Mordmüller, MD

Role: PRINCIPAL_INVESTIGATOR

Eberhard Karls University of Tübingen, Germany

Locations

Eberhard Karls University of Tübingen, Germany

Tübingen, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 26245196 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25889522 (View on PubMed)

Requena P, Gomez-Perez GP, McCall MBB, Barrios D, Aguilar R, Fernandez-Morata J, Vidal M, Campo JJ, Sanchez C, Yazdabankhsh M, Sim BKL, Hoffman SL, Kremsner P, Lell B, Mordmuller B, Dobano C, Moncunill G. Effect of controlled human Plasmodium falciparum infection on B cell subsets in individuals with different levels of malaria immunity. Med Microbiol Immunol. 2025 Sep 27;214(1):47. doi: 10.1007/s00430-025-00847-x.

Reference Type: DERIVED

PMID: 41014333 (View on PubMed)

Related Links

http://www.malariajournal.com/content/14/1/117

Publication of trials results

Other Identifiers

TUCHMI-001

Identifier Type: -

Identifier Source: org_study_id