Controlled Human Malaria Infection Transmission Model - Phase A (CHMI-TransMod)

May 22, 2024 updated by: University of Oxford

Safety and Feasibility of a Malaria Transmission Model in Semi-immune Kenyan Adults Using Plasmodium Falciparum Sporozoites

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Malaria is a disease of major public health importance. The only vaccine available is partially effective and targets the pre-erythrocytic stages of the life cycle. Thus, there is a need to identify other potential vaccine targets as well as to develop models to test vaccine efficacy, especially that of transmission-blocking vaccines. Controlled human malaria infection (CHMI) has been shown to be an important tool for the assessment of the efficacy of novel malaria vaccines and drugs. CHMI also allows for the evaluation of immunity to malaria and monitoring of parasite growth rates in vivo. This is particularly useful in individuals from endemic areas with varying levels of exposure and immunity to malaria. Thus, CHMI in individuals with prior exposure to malaria has potential to accelerate malaria vaccine development. In this study, the aim is to use CHMI in semi-immune adults to develop a model to assess transmissibility of malaria infection to mosquitoes, to study immune responses that are directed against sexual stages that might block transmission, and as a platform to test vaccines. To achieve this, the study will be carried out in two phases A (N=45 participants) and B (N=60 participants) over a period of 4-6months. Parasite dose will be varied in individuals enrolled for CHMI and use of low-doses of anti-malarial drugs to promote the production of gametocytes in vivo (Phase A) and demonstrate transmissibility in mosquito feeding assays (Phase B). Thus, the main outcomes of the study will be: (1) optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure; (2) use of sub-curative anti-malaria treatment for induction of gametocytes; and (3) infection of mosquitoes in mosquito feeding assays by induced gametocytes. To achieve this, up to 250 semi-immune adults will be recruited from known areas of malaria endemicity in Kenya with varying exposure to malaria undergo screening procedures after informed consent to enrol 105 individuals to conduct CHMI studies with serial quantitative polymerase chain reaction (PCR) to measure asexual parasite growth and induction of transmission stages in vivo. In addition, comprehensively characterize immunity and identify targets in relation to function assessed by various laboratory assays.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Mainga Hamaluba, MD
  • Phone Number: +254709983946

Study Locations

  • Kenya
      • Kilifi, Kenya, 80108
        • KEMRI-Wellcome Trust Research Programme

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Healthy adults aged 18 to 45 years.
  2. Able and willing (in the Investigator's opinion) to comply with all study requirements.
  3. Informed consent.
  4. 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).

Exclusion Criteria:

  1. Body weight of less than 50kg or body mass index (BMI) less than 18 or greater than 25 kg/m2 at screening.
  2. 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).
  3. Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
  4. Current participation in another clinical trial or recent participation within 12 weeks of enrolment.
  5. Prior receipt of an investigational malaria vaccine.
  6. 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.
  7. Use of immunoglobulins or blood products within 3 months prior to enrolment.
  8. Any serious medical condition reported or identified during screening that increases the risk of CHMI.
  9. Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.
  10. Women only; pregnancy, or an intention to become pregnant during the duration of the study.
  11. Sickle cell trait or disease.
  12. History of drug or alcohol abuse.
  13. Known hypersensitivity to or contraindications for use of artemether-lumefantrine, chloroquine, piperaquine, primaquine, sulfadoxine-pyrimethamine, or history of severe (allergic) reactions to mosquito bites.
  14. Confirmed gametocyte positivity at screening and/or a day before challenge

  15. Confirmed parasite positive by PCR a day before challenge i.e. at C-1. Exclusion Criterion on Day of Challenge

    • Acute disease, defined as moderate or severe illness with or without fever (temperature >37.5 degrees Celcius).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group 1: PfSPZ 6,400

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
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites
Other Names:
  • NF54 Plasmodium falciparum malaria challenge
Drug: Sulfadoxine-Pyrimethamine
Sub-curative 500mg/25mg single dose regimen
Other Names:
  • Fansidar
Drug: Piperaquine
Sub-curative 480mg single dose regimen
Other Names:
  • Piperaquine Phosphate
Drug: Artemether lumefantrine
Three day curative regimen 20mg/120mg
Other Names:
  • Coartem
Drug: Primaquine
Single low dose regimen 0.25 mg base/kg
Experimental: Group 1: PfSPZ 12,800

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
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites
Other Names:
  • NF54 Plasmodium falciparum malaria challenge
Drug: Sulfadoxine-Pyrimethamine
Sub-curative 500mg/25mg single dose regimen
Other Names:
  • Fansidar
Drug: Piperaquine
Sub-curative 480mg single dose regimen
Other Names:
  • Piperaquine Phosphate
Drug: Artemether lumefantrine
Three day curative regimen 20mg/120mg
Other Names:
  • Coartem
Drug: Primaquine
Single low dose regimen 0.25 mg base/kg
Experimental: Group 3: PfSPZ 25,600

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
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites
Other Names:
  • NF54 Plasmodium falciparum malaria challenge
Drug: Sulfadoxine-Pyrimethamine
Sub-curative 500mg/25mg single dose regimen
Other Names:
  • Fansidar
Drug: Piperaquine
Sub-curative 480mg single dose regimen
Other Names:
  • Piperaquine Phosphate
Drug: Artemether lumefantrine
Three day curative regimen 20mg/120mg
Other Names:
  • Coartem
Drug: Primaquine
Single low dose regimen 0.25 mg base/kg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure
Time Frame: Up to 42 days post infection with PfSPZ challenge
Magnitude and frequency of adverse events in the study groups
Up to 42 days post infection with PfSPZ challenge
Prevalence of gametocytes
Time Frame: Up to 42 days post infection with PfSPZ challenge
Prevalence of gametocytes as determined by qRT-PCR
Up to 42 days post infection with PfSPZ challenge

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Use of sub-curative anti-malaria treatment for induction of gametocytes
Time Frame: Up to 42 days post infection with PfSPZ challenge
Density of gametocytes as measured by qRT-PCR
Up to 42 days post infection with PfSPZ challenge
Peak density and time point of gametocytaemia
Time Frame: Up to 42 days post infection with PfSPZ challenge
Peak density and peak time point of gametocytes by drug-regimen and determine the area under the curve of density over time
Up to 42 days post infection with PfSPZ challenge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Oxford

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sanaria Inc.
KEMRI-Wellcome Trust Collaborative Research Program
Kenya Medical Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 22, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 19, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 21, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KEMRI/SERU/CGMR-C/117/3759
  • OxTREC 48-18 (Other Identifier: Oxford Tropica Research Ethics Committee)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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