MalariaNCT04788862
A Study of Blood-stage Controlled Human Plasmodium Falciparum Malaria Infection in Tanzania
A study testing P. falciparum infected erythrocytes in people with Malaria and Plasmodium Falciparum, run by University of Oxford at 1 site in Tanzania.
Trial summary
This will be a single-centre, open label trial to determine the safety and feasibility of CHMI model using Plasmodium falciparum-infected cryopreserved erythrocytes administered to healthy Tanzanian adults with varying prior exposure to P. falciparum. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Malaria, Plasmodium Falciparum
- What is being tested?
- P. falciparum infected erythrocytes
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteTanzania
- Study dates
- 18 Jul 2022to 24 Feb 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Volunteer being adult male aged ≥ 18 and ≤ 35 years, and in good health.
- Volunteer a resident in Bagamoyo town or rural areas of Bagamoyo district for the past 6 months
- Able and willing to complete the informed consent process conducted in English
- Volunteer has adequate understanding of the procedures of the study and is able and willing (in the investigator's opinion) to comply with all study requirements.
- Volunteer is willing to complete an informed consent questionnaire and is able to answer all questions correctly in a maximum of two attempts.
- Volunteer is able to communicate well with the investigator and is willing to be monitored in an inpatient setting for 28 days after challenge with infected erythrocytes.
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- The volunteer agrees to refrain from blood donation throughout the study period.
- Volunteer agrees to refrain from intensive physical exercise (disproportionate to the volunteer's usual daily activity or exercise routine) during the malaria challenge period.
- Volunteer has signed written informed consent to participate in the trial.
Who cannot join
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, gastrointestinal, renal, hepatic, neurological, dermatological (e.g. psoriasis, contact dermatitis etc.), allergy, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results.
- A heightened risk of cardiovascular disease, as determined by: an estimated ten-year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.
- Body mass index (BMI) of <18 or >30 Kg/m2
- A medical history of functional asplenia.
- History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
- Confirmed parasite positive by PCR a day before challenge i.e., at C-1.
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- Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)
- Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral antihistamines exempted) or expected use of such during the study period
- Any recent or current systemic therapy with an antibiotic or drug with potential antimalarial activity (chloroquine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (allowable time frame for use at the Investigator's discretion).
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
- Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
- History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.
- Previous participation in any malaria investigational product study (allowable time frame for use at the Investigator's discretion)
- Known hypersensitivity to or contra-indications (including co-medication) for use of chloroquine, artemether-lumefantrine, Primaquine or history of severe (allergic) reactions to blood transfusion.
- Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
- Being an employee or relative of an employee of Ifakara Health Institute.
- Any other condition or situation that would, in the opinion of the investigator, place the volunteer at an unacceptable risk of injury or render the volunteer unable to meet the requirements of the protocol.
- Acute disease, defined as moderate or severe illness with or without fever
- 2. Current COVID-19 infection, defined as ongoing symptoms with positive COVID-19 PCR or rapid antigen test taken during current illness or positive COVID-19 PCR or rapid antigen test within preceding 7 days without symptoms.
- History of close contact with COVID-19 confirmed case within preceding 14 days
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open Label Trial to Establish a Blood-stage Controlled Human Malaria Infection Model and Determine Its Safety in Healthy Tanzanian Adults With Varying Prior Exposure to P. Falciparum
This will be a single-centre, open label trial to determine the safety and feasibility of CHMI model using Plasmodium falciparum-infected cryopreserved erythrocytes administered to healthy Tanzanian adults with varying prior exposure to P. falciparum.
Read the detailed description
This study will be a single-centre controlled human malaria infection study using adults with varying degrees of prior exposure to P. falciparum. The study will take place at Bagamoyo Clinical Trail Facility of the Ifakara Health Institute, located in Bagamoyo town (about 60 km north of Dar es Salaam).
Twelve healthy male adults aged 18 to 35 years will be recruited into two cohorts of high and low previous exposure consisting of 6 volunteers each as determined by anti-schizont antibody levels. Up to 5 back-up volunteers will be also be recruited and may take the place of another volunteer should they withdraw or become ineligible prior to challenge.
Participants will be infected via IV administration of Plasmodium falciparum-infected human erythrocytes of the chloroquine-susceptible 3D7 strain. Participants will then be closely monitored in a clinical trial facility for a maximum of 31 (28 days plus 3 days of treatment with anti-malarial drugs) days while undergoing frequent clinical and laboratory assessment. Volunteers who do not reach malaria treatment criteria as per protocol at day 28 (C+28) will be treated presumptively with antimalarial medications (ALU + a single low dose primaquine) under direct observation and will be discharged upon completion of treatment and on discretion of the study clinician.
Identifying data will not be included on any trial documentation (other than signed consent) and participants will be referred to by the trial study ID number. The study will be funded primarily by EDCTP grant supporting the evaluation of Multi-Stage Malaria Vaccine.
- Conditions
- Malaria, Plasmodium Falciparum
- Being tested
- P. falciparum infected erythrocytes
- Keywords
- Malaria Challenge, Controlled Human Malaria Challenge
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P. falciparum infected erythrocytesBiological
Chloroquine sensitive P. falciparum 3D7-infected red blood cells, thawed and prepared under strict aseptic conditions, will be used as a challenge agent.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: High prior P. falciparum exposure | Experimental | 6 participants with high previous malaria exposure will be infected via IV administration of Plasmodium falciparum-infected human erythrocytes (planned dose of 1000 iRBCs) of the chloroquine-susceptible 3D7 strain. Receives: Biological: P. falciparum infected erythrocytes |
| Group 2: Low prior P. falciparum exposure | Experimental | 6 participants with no or low previous malaria exposure will be infected via IV administration of Plasmodium falciparum-infected human erythrocytes (planned dose of 1000 iRBCs) of the chloroquine-susceptible 3D7 strain. Receives: Biological: P. falciparum infected erythrocytes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of adverse events to assess the safety of controlled blood-stage P. falciparum
Frequency and severity of clinical and laboratory Adverse Events and Serious Adverse Events
Measured: 98 days
Development of parasitaemia to assess the feasibility of controlled blood-stage P. falciparum
Proportion of participants who develop detectable parasitaemia post-CHMI as measured by qPCR
Measured: 28 days
Development of parasitaemia to assess the feasibility of controlled blood-stage P. falciparum
Proportion of participants who develop sustained parasitaemia detectable by qPCR that is then spontaneously cleared
Measured: 28 days
Parasite multiplication rates to assess the feasibility of controlled blood-stage P. falciparum
Determine parasite multiplication rates as calculated by fitting established models to quantitative PCR data, as routinely done in the published studies (Payne et al., JID 2016; Minassian et al., submitted)
Measured: 28 days
Secondary outcomes (5)
Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis
- falciparum specific immunogenicity following P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses. Determined by ELISA (concentration of antibodies)
Measured: 98 days
Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis
- falciparum specific immunogenicity following P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses. Determined by ELISpot (spots per 10^x PBMCs)
Measured: 98 days
Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis
- falciparum specific immunogenicity following P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses. Determined by flow cytometry (% of immune cell sub-population)
Measured: 98 days
To determine the effect of pre-exposure to malaria on parasite multiplication rates following controlled blood-stage P. falciparum infection.
Comparison of PMRs between participants with low and high prior exposure to P. falciparum.
Measured: 28 days
To determine if malaria infection following inoculation of P. falciparum is caused by the inoculum parasite strain and not wild-type strains
Determine whole genome sequences (via whole genome analysis) following controlled blood-stage P. falciparum infection to confirm malaria infection is with inoculum strain and not wild-type parasite
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2021
- Study start18 Jul 2022
- Primary completion24 Feb 2023
- Study completion24 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Ifakara Health Institute
- Responsible party
- Sponsor
- Investigators
- Angela Minassian, Dr, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04788862
- Sponsor's protocol ID
- VAC083
- Status last verified
- May 2023
- First submitted
- 25 Feb 2021
- Last updated
- 24 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Trial to Establish a Blood-stage Controlled Human Malaria Infection Model and Determine Its Safety in Healthy Tanzanian Adults With Varying Prior Exposure to P. Falciparum
- ClinicalTrials.gov ID
- NCT04788862
- Acronym / sponsor ID
- VAC083
- Conditions
- Malaria, Plasmodium Falciparum
- Keywords
- Malaria Challenge, Controlled Human Malaria Challenge
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Ifakara Health Institute
- Study start
- 18 Jul 2022 (actual)
- Primary completion
- 24 Feb 2023 (actual)
- Study completion
- 24 Feb 2023 (actual)
- First posted
- 9 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a single-centre, open label trial to determine the safety and feasibility of CHMI model using Plasmodium falciparum-infected cryopreserved erythrocytes administered to healthy Tanzanian adults with varying prior exposure to P. falciparum.
Detailed description
This study will be a single-centre controlled human malaria infection study using adults with varying degrees of prior exposure to P. falciparum. The study will take place at Bagamoyo Clinical Trail Facility of the Ifakara Health Institute, located in Bagamoyo town (about 60 km north of Dar es Salaam).
Twelve healthy male adults aged 18 to 35 years will be recruited into two cohorts of high and low previous exposure consisting of 6 volunteers each as determined by anti-schizont antibody levels. Up to 5 back-up volunteers will be also be recruited and may take the place of another volunteer should they withdraw or become ineligible prior to challenge.
Participants will be infected via IV administration of Plasmodium falciparum-infected human erythrocytes of the chloroquine-susceptible 3D7 strain. Participants will then be closely monitored in a clinical trial facility for a maximum of 31 (28 days plus 3 days of treatment with anti-malarial drugs) days while undergoing frequent clinical and laboratory assessment. Volunteers who do not reach malaria treatment criteria as per protocol at day 28 (C+28) will be treated presumptively with antimalarial medications (ALU + a single low dose primaquine) under direct observation and will be discharged upon completion of treatment and on discretion of the study clinician.
Identifying data will not be included on any trial documentation (other than signed consent) and participants will be referred to by the trial study ID number. The study will be funded primarily by EDCTP grant supporting the evaluation of Multi-Stage Malaria Vaccine.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: High prior P. falciparum exposure | Experimental | Biological: P. falciparum infected erythrocytes6 participants with high previous malaria exposure will be infected via IV administration of Plasmodium falciparum-infected human erythrocytes (planned dose of 1000 iRBCs) of the chloroquine-susceptible 3D7 strain. |
| Group 2: Low prior P. falciparum exposure | Experimental | Biological: P. falciparum infected erythrocytes6 participants with no or low previous malaria exposure will be infected via IV administration of Plasmodium falciparum-infected human erythrocytes (planned dose of 1000 iRBCs) of the chloroquine-susceptible 3D7 strain. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Volunteer being adult male aged ≥ 18 and ≤ 35 years, and in good health.
- Volunteer a resident in Bagamoyo town or rural areas of Bagamoyo district for the past 6 months
- Able and willing to complete the informed consent process conducted in English
- Volunteer has adequate understanding of the procedures of the study and is able and willing (in the investigator's opinion) to comply with all study requirements.
- Volunteer is willing to complete an informed consent questionnaire and is able to answer all questions correctly in a maximum of two attempts.
Key exclusion criteria (20 listed)
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, gastrointestinal, renal, hepatic, neurological, dermatological (e.g. psoriasis, contact dermatitis etc.), allergy, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results.
- A heightened risk of cardiovascular disease, as determined by: an estimated ten-year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.
- Body mass index (BMI) of <18 or >30 Kg/m2
- A medical history of functional asplenia.
- History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| P. falciparum infected erythrocytesChloroquine sensitive P. falciparum 3D7-infected red blood cells, thawed and prepared under strict aseptic conditions, will be used as a challenge agent. | Biological | Group 1: High prior P. falciparum exposure, Group 2: Low prior P. falciparum exposure |
Primary outcome
Occurrence of adverse events to assess the safety of controlled blood-stage P. falciparum
Time frame: 98 days
Frequency and severity of clinical and laboratory Adverse Events and Serious Adverse Events
Development of parasitaemia to assess the feasibility of controlled blood-stage P. falciparum
Time frame: 28 days
Proportion of participants who develop detectable parasitaemia post-CHMI as measured by qPCR
Development of parasitaemia to assess the feasibility of controlled blood-stage P. falciparum
Time frame: 28 days
Proportion of participants who develop sustained parasitaemia detectable by qPCR that is then spontaneously cleared
Parasite multiplication rates to assess the feasibility of controlled blood-stage P. falciparum
Time frame: 28 days
Determine parasite multiplication rates as calculated by fitting established models to quantitative PCR data, as routinely done in the published studies (Payne et al., JID 2016; Minassian et al., submitted)
5 secondary outcomes
Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis
Time frame: 98 days
Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis
Time frame: 98 days
Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis
Time frame: 98 days
To determine the effect of pre-exposure to malaria on parasite multiplication rates following controlled blood-stage P. falciparum infection.
Time frame: 28 days
To determine if malaria infection following inoculation of P. falciparum is caused by the inoculum parasite strain and not wild-type strains
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela Minassian, Dr principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing P. falciparum infected erythrocytes in people with Malaria and Plasmodium Falciparum, run by University of Oxford at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of adverse events to assess the safety of controlled blood-stage P. falciparum (time frame: 98 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023.