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

NCT01624961 | Completed Phase 1 DMC

• 1 other identifier: TUCHMI-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

Controlled human malaria infection (CHMI); Malaria challenge; Plasmodium falciparum; PfSPZ Challenge

Outcome Measures

Primary Outcomes (1)

• The infectivity of the administration regimens will be assessed by thick film microscopy and PCR for P. falciparum DNA.

  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 Outcomes (2)

• The time from parasite inoculation to first detection of blood stage parasitemia will be assessed by thick blood film microscopy.

  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

  Screening to Day 168

Study Arms (5)

50 PfSPZ IV

EXPERIMENTAL

PfSPZ Challenge

Biological: PfSPZ Challenge

200 PfSPZ IV

EXPERIMENTAL

PfSPZ Challenge

Biological: PfSPZ Challenge

800 PfSPZ IV

EXPERIMENTAL

PfSPZ Challenge

Biological: PfSPZ Challenge

3200 PfSPZ IV

EXPERIMENTAL

PfSPZ Challenge

Biological: PfSPZ Challenge

2500 PfSPZ ID

EXPERIMENTAL

PfSPZ Challenge

Biological: PfSPZ Challenge

Interventions

PfSPZ Challenge BIOLOGICAL

PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites.

Also known as: Aseptic, cryopreserved P. falciparum sporozoites

200 PfSPZ IV; 2500 PfSPZ ID; 3200 PfSPZ IV; 50 PfSPZ IV; 800 PfSPZ IV

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanaria Inc.: lead
• Institute of Tropical Medicine, University of Tuebingen: collaborator

Study Sites (1)

Eberhard Karls University of Tübingen, Germany

Tübingen, D-72074, Germany

Location

Related Publications (3)

• 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.

  PMID: 26245196 BACKGROUND

• 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.

  PMID: 25889522 RESULT

• 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.

  PMID: 41014333 DERIVED

Related Links

• Publication of trials results

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Benjamin G Mordmüller, MD

  Eberhard Karls University of Tübingen, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2012
• First Posted: June 21, 2012
• Study Start: June 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: February 1, 2013
• Last Updated: April 4, 2016

Record last verified: 2016-03

Locations

DE (1)