Controlled Human Malaria Infection Transmission Model - Phase A

NCT04280692 | Suspended Phase 1 DMC

• 2 other identifiers: KEMRI/SERU/CGMR-C/117/3759OxTREC 48-18
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This is to develop a model to test the efficacy of vaccines and/or drugs designed to block transmission of malaria to mosquitoes and to identify the targets of transmission-blocking immunity to malaria.

Conditions

Malaria,Falciparum

Keywords

PfSPZ; Kenya; Gametocytes; Transmission; CHMI; Challenge; semi-immune adults

Outcome Measures

Primary Outcomes (2)

• Safety and optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure

  Magnitude and frequency of adverse events in the study groups

  Up to 42 days post infection with PfSPZ challenge

• Prevalence of gametocytes

  Prevalence of gametocytes as determined by qRT-PCR

  Up to 42 days post infection with PfSPZ challenge

Secondary Outcomes (2)

• Use of sub-curative anti-malaria treatment for induction of gametocytes

  Up to 42 days post infection with PfSPZ challenge

• Peak density and time point of gametocytaemia

  Up to 42 days post infection with PfSPZ challenge

Study Arms (3)

Group 1: PfSPZ 6,400

EXPERIMENTAL

Group 1 will receive a malaria infection by direct venous inoculation (DVI) with PfSPZ Challenge at a dose of 6,400 sporozoites. Group 1 will be randomised (1:1) to receive either sub-curative Sulfadoxine-Pyrimethamine (SP) (500mg/25mg) or Piperaquine (PIP) (480mg). Group 1 will receive a final curative treatment of Artemether-Lumefantrine (AL) with single low dose Primaquine (SLDPQ)

Biological: PfSPZ Challenge; Drug: Sulfadoxine-Pyrimethamine; Drug: Piperaquine; Drug: Artemether lumefantrine; Drug: Primaquine

Group 1: PfSPZ 12,800

EXPERIMENTAL

Group 2 will receive a malaria infection by direct venous inoculation (DVI) with PfSPZ Challenge at a dose of 12,800 sporozoites Group 2 will be randomised (1:1) to receive either sub-curative Sulfadoxine-Pyrimethamine (SP) (500mg/25mg) or Piperaquine (PIP) (480mg). Group 2 will receive a final curative treatment of Artemether-Lumefantrine (AL) with single low dose Primaquine (SLDPQ)

Biological: PfSPZ Challenge; Drug: Sulfadoxine-Pyrimethamine; Drug: Piperaquine; Drug: Artemether lumefantrine; Drug: Primaquine

Group 3: PfSPZ 25,600

EXPERIMENTAL

Group 3 will receive a malaria infection by direct venous inoculation (DVI) with PfSPZ Challenge at a dose of 25,600 sporozoites Group 3 will be randomised (1:1) to receive either sub-curative Sulfadoxine-Pyrimethamine (SP) (500mg/25mg) or Piperaquine (PIP) (480mg). Group 3 will receive a final curative treatment of Artemether-Lumefantrine (AL) with single low dose Primaquine (SLDPQ)

Biological: PfSPZ Challenge; Drug: Sulfadoxine-Pyrimethamine; Drug: Piperaquine; Drug: Artemether lumefantrine; Drug: Primaquine

Interventions

PfSPZ Challenge BIOLOGICAL

Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites

Also known as: NF54 Plasmodium falciparum malaria challenge

Group 1: PfSPZ 12,800; Group 1: PfSPZ 6,400; Group 3: PfSPZ 25,600

Sulfadoxine-Pyrimethamine DRUG

Sub-curative 500mg/25mg single dose regimen

Also known as: Fansidar

Group 1: PfSPZ 12,800; Group 1: PfSPZ 6,400; Group 3: PfSPZ 25,600

Piperaquine DRUG

Sub-curative 480mg single dose regimen

Also known as: Piperaquine Phosphate

Group 1: PfSPZ 12,800; Group 1: PfSPZ 6,400; Group 3: PfSPZ 25,600

Artemether lumefantrine DRUG

Three day curative regimen 20mg/120mg

Also known as: Coartem

Group 1: PfSPZ 12,800; Group 1: PfSPZ 6,400; Group 3: PfSPZ 25,600

Primaquine DRUG

Single low dose regimen 0.25 mg base/kg

Group 1: PfSPZ 12,800; Group 1: PfSPZ 6,400; Group 3: PfSPZ 25,600

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.
• Informed consent.
• Use of effective method of contraception for duration of study (women only). We will ask the female volunteers to come with their family planning records to verify. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject's entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).

You may not qualify if:

• Body weight of less than 50kg or body mass index (BMI) less than 18 or greater than 25 kg/m2 at screening.
• Use of systemic antibiotics with known antimalarial activity within 30 days of administration of PfSPZ Challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).
• Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
• Current participation in another clinical trial or recent participation within 12 weeks of enrolment.
• Prior receipt of an investigational malaria vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed). This will also include Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) positivity.
• Use of immunoglobulins or blood products within 3 months prior to enrolment.
• Any serious medical condition reported or identified during screening that increases the risk of CHMI.
• Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.
• Women only; pregnancy, or an intention to become pregnant during the duration of the study.
• Sickle cell trait or disease.
• History of drug or alcohol abuse.
• Known hypersensitivity to or contraindications for use of artemether-lumefantrine, chloroquine, piperaquine, primaquine, sulfadoxine-pyrimethamine, or history of severe (allergic) reactions to mosquito bites.
• Confirmed gametocyte positivity at screening and/or a day before challenge
• Acute disease, defined as moderate or severe illness with or without fever (temperature \>37.5 degrees Celcius).

Sponsors & Collaborators

• University of Oxford: lead
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator
• Sanaria Inc.: collaborator
• Kenya Medical Research Institute: collaborator

Study Sites (1)

KEMRI-Wellcome Trust Research Programme

Kilifi, 80108, Kenya

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

fanasil, pyrimethamine drug combination; piperaquine; Artemether, Lumefantrine Drug Combination; Primaquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2020
• First Posted: February 21, 2020
• Study Start: August 22, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 23, 2024

Record last verified: 2024-05

Locations

KE (1)