Effect of Plasmodium Falciparum Exposure and Sickle Cell Trait on Infection Rates and Kinetics After IV Administration of PfSPZ Challenge

NCT02237586 | Completed Phase 1 DMC

• 1 other identifier: LACHMI-001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed to establish infectivity of Plasmodium falciparum sporozoites (PfSPZ) via intravenous (IV) administration in three groups with different malaria immunity-status:

1. 1.Adults with a history of lifelong malaria exposure without sickle cell trait (HbAA)
2. 2.Adults with a history of lifelong malaria exposure with sickle cell trait (HbAS)
3. 3.Adults without previous malaria episodes without sickle cell trait (HbAA)

Conditions

Plasmodium Falciparum Malaria; Malaria

Keywords

Plasmodium falciparum malaria; Malaria; PfSPZ Challenge; Controlled Human Malaria Infection (CHMI); Sickle Cell Trait; Sporozoites

Outcome Measures

Primary Outcomes (2)

• Days from inoculation to start of malaria episode

  The time from parasite inoculation to first detection of malaria will be assessed by thick blood film microscopy and a clinical questionnaire. Malaria is defined as both parasitemia and clinical symptoms suggestive of malaria.

  From day of injection until day 28

• Frequency, incidence and nature of adverse events

  The safety of PfSPZ Challenge administered 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.

  From day of injection until day 28

Secondary Outcomes (1)

• Dynamics of P. falciparum parasite growth

  From day 6 after injection until approximately day 28

Other Outcomes (2)

• Cellular and humoral immune responses against parasites

  From screening until 6 months

• Stage specific expression patterns of parasite genes

  From screening until 6 months

Study Arms (3)

Group IA

EXPERIMENTAL

Adults with naturally acquired immunity and HbAA (Group IA, n=10) As any parasitemia other than PfSPZ will interfere with results, volunteers will undergo a treatment course against P. falciparum with a five-day course of 12-hourly 5 mg/kg clindamycin (corresponds to a 300 mg tablet of clindamycin base administered twice daily). This will be completed no less than three days prior to CHMI. The initial challenge dose of 3,200 PfSPZ Challenge will be administered once intravenously. If 50% or less of volunteers become parasitemic in Groups IA or IS, 10 additional volunteers will be enrolled and challenged with 12,800 PfSPZ. Effective treatment will be initiated immediately upon development of parasitemia together with the presence of symptoms associated with malaria.

Biological: PfSPZ Challenge

Group IS

EXPERIMENTAL

Adults with naturally acquired immunity and HbAS (Group IS, n=10) As any parasitemia other than PfSPZ will interfere with results, volunteers will undergo a treatment course against P. falciparum with a five-day course of 12-hourly 5 mg/kg clindamycin (corresponds to a 300 mg tablet of clindamycin base administered twice daily). This will be completed no less than three days prior to CHMI. The initial challenge dose of 3,200 PfSPZ Challenge will be administered once intravenously. If 50% or less of volunteers become parasitemic in Groups IA or IS, 10 additional volunteers will be enrolled and challenged with 12,800 PfSPZ. Effective treatment will be initiated immediately upon development of parasitemia together with the presence of symptoms associated with malaria.

Biological: PfSPZ Challenge

Group NI

EXPERIMENTAL

Adults without previous exposure to malaria and HbAA (Group NI, n=5) As any parasitemia other than PfSPZ will interfere with results, volunteers will undergo a treatment course against P. falciparum with a five-day course of 12-hourly 5 mg/kg clindamycin (corresponds to a 300 mg tablet of clindamycin base administered twice daily). This will be completed no less than three days prior to CHMI. The initial challenge dose of 3,200 PfSPZ Challenge administered once intravenously should lead to consistent infection in naïve adults (15/15 in prior studies) and thus should infect all volunteers in Group NI. Effective treatment will be initiated immediately upon development of parasitemia together with the presence of symptoms associated with malaria.

Biological: PfSPZ Challenge

Interventions

PfSPZ Challenge BIOLOGICAL

live, aseptic, cryopreserved P. falciparum sporozoites

Group IA; Group IS; Group NI

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult aged 18 to 30 years
• Able and willing (in the investigator's opinion) to comply with all study requirements
• 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 two curative anti-malarial regimens
• 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 ≥10 g/dl for women and ≥12 g/dl for men
• \- History of long term residence (\>10 years) in area known to have significant transmission of P. falciparum -

You may not qualify if:

• Use of anti-malarials within 30 days of study enrolment
• 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
• Immunization with more than 1 other vaccines within the past month.
• HIV infection
• Hemoglobin SS
• 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
• 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: artemether/lumefantrine or atovaquone/proguanil.
• 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
• History of epileptic seizures

Sponsors & Collaborators

• Sanaria Inc.: lead
• Centre de Recherche Médicale de Lambaréné: collaborator
• Institute of Tropical Medicine, University of Tuebingen: collaborator

Study Sites (1)

Centre de Recherches Médicales de Lambaréné

Lambaréné, BP 118, Gabon

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Malaria, Falciparum; Malaria; Sickle Cell Trait

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Anemia, Sickle Cell; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Bertrand Lell, MD

  Centre de Recherche Médicale de Lambaréné

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: September 11, 2014
• Study Start: July 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: February 1, 2015
• Last Updated: April 23, 2015

Record last verified: 2015-04

Locations

GA (1)