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

Primary Purpose

Malaria,Falciparum

Status

Active

Phase

Phase 1

Locations

Kenya

Study Type

Interventional

Intervention

PfSPZ Challenge

Sulfadoxine-Pyrimethamine

Piperaquine

Artemether lumefantrine

Primaquine

About this trial

This is an interventional basic science trial for Malaria,Falciparum focused on measuring PfSPZ, Kenya, Gametocytes, Transmission, CHMI, Challenge, semi-immune adults

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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).

Exclusion Criteria:

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
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).

Sites / Locations

KEMRI-Wellcome Trust Research Programme

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Group 1: PfSPZ 6,400

Group 1: PfSPZ 12,800

Group 3: PfSPZ 25,600

Arm Description

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)

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)

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)

Outcomes

Primary Outcome Measures

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

Prevalence of gametocytes

Prevalence of gametocytes as determined by qRT-PCR

Secondary Outcome Measures

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

Density of gametocytes as measured by qRT-PCR

Peak density and time point of gametocytaemia

Peak density and peak time point of gametocytes by drug-regimen and determine the area under the curve of density over time

Full Information

NCT ID

NCT04280692

First Posted

February 19, 2020

Last Updated

March 9, 2023

Sponsor

University of Oxford

Collaborators

KEMRI-Wellcome Trust Collaborative Research Program, Sanaria Inc., Kenya Medical Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT04280692

Brief Title

Controlled Human Malaria Infection Transmission Model - Phase A

Acronym

CHMI-TransMod

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 22, 2022 (Actual)

Primary Completion Date

April 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Oxford

Collaborators

KEMRI-Wellcome Trust Collaborative Research Program, Sanaria Inc., Kenya Medical Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malaria,Falciparum

Keywords

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: PfSPZ 6,400

Arm Type

Experimental

Arm Description

Arm Title

Group 1: PfSPZ 12,800

Arm Type

Experimental

Arm Description

Arm Title

Group 3: PfSPZ 25,600

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

PfSPZ Challenge

Other Intervention Name(s)

NF54 Plasmodium falciparum malaria challenge

Intervention Description

Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites

Intervention Type

Drug

Intervention Name(s)

Sulfadoxine-Pyrimethamine

Other Intervention Name(s)

Fansidar

Intervention Description

Sub-curative 500mg/25mg single dose regimen

Intervention Type

Drug

Intervention Name(s)

Piperaquine

Other Intervention Name(s)

Piperaquine Phosphate

Intervention Description

Sub-curative 480mg single dose regimen

Intervention Type

Drug

Intervention Name(s)

Artemether lumefantrine

Other Intervention Name(s)

Coartem

Intervention Description

Three day curative regimen 20mg/120mg

Intervention Type

Drug

Intervention Name(s)

Primaquine

Intervention Description

Single low dose regimen 0.25 mg base/kg

Primary Outcome Measure Information:

Title

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

Description

Magnitude and frequency of adverse events in the study groups

Time Frame

Up to 42 days post infection with PfSPZ challenge

Title

Prevalence of gametocytes

Description

Prevalence of gametocytes as determined by qRT-PCR

Time Frame

Up to 42 days post infection with PfSPZ challenge

Secondary Outcome Measure Information:

Title

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

Description

Density of gametocytes as measured by qRT-PCR

Time Frame

Up to 42 days post infection with PfSPZ challenge

Title

Peak density and time point of gametocytaemia

Description

Peak density and peak time point of gametocytes by drug-regimen and determine the area under the curve of density over time

Time Frame

Up to 42 days post infection with PfSPZ challenge

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

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. 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). Exclusion Criteria: 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 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).

Facility Information:

Facility Name

KEMRI-Wellcome Trust Research Programme

City

Kilifi

ZIP/Postal Code

80108

Country

Kenya

12. IPD Sharing Statement

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Controlled Human Malaria Infection Transmission Model - Phase A

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