MalariaCHMI-Gambia1NCT03496454
Susceptibility of Gambian Adults to PfSPZ-Challenge Infection in the Controlled Human Malaria Infection Model
A study testing PfSPZ Challenge in people with Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
Trial summary
Controlled human malaria infection (CHMI) is an important tool for the assessment of the efficacy of novel malaria vaccines and drugs prior to field trials. CHMI also allows for the evaluation of immunity to malaria and parasite growth rates in vivo and thus allows for the assessment of the natural acquisition and… 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
- What is being tested?
- PfSPZ Challenge
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteThe Gambia
- Study dates
- 29 Mar 2018to 5 Dec 2018
- 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
- Males aged ≥ 18 and ≤ 35 years and in good health;
- At least 4 completed years of secondary education;
- Adequate understanding of the procedures of the study in English language;
- Willing (in the investigator's opinion) to comply with all study requirements;
- Willing to complete an informed consent questionnaire and is able to answer all questions correctly;
- Signed written informed consent to participate in the trial;
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- Willing to take a course of curative anti-malaria medication;
- Able to communicate well with the investigator and is available to attend all study visits;
- Willing to stay in a hotel close to the trial centre OR willing to be hospitalized in the CSD of MRCG during a part of the study (day 5 post-infection until day 3 after treatment);
- Reachable (24/7) by mobile telephone throughout the entire study period;
- Agrees to refrain from blood donation or for other purposes throughout the study period and after the end of their involvement in the study according to the local blood banking eligibility criteria.
- Agrees to refrain from intensive physical exercise (disproportionate to the participant's usual daily activity or exercise routine) during the malaria challenge period;
- Hb ≥12 g/dl.
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, renal, hepatic, neurological, dermatological, endocrine,malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the participant during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following
- Body weight <50 kg or Body Mass Index (BMI) <18 or >30 kg/m2 at screening.
- 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's, 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.
- A medical history of functional asplenia, G6PD disease or α-thalassaemia disease.
- Positive test for sickle cell disease.
- History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
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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 anti-histamines exempted) or expected use of such during the study period.
- Any recent or current systemic therapy with an antibiotic or drug with potential anti-malarial activity (chloroquine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (Allowable timeframe 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.
- Suspicion or history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.
- Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.
- qPCR positive for Pf parasites at screening or previous participation in any malaria (vaccine) study.
- Known hypersensitivity to artemether-lumefantrine.
- Current use of any drug that is metabolised by the cytochrome enzyme CYP2D6 (e.g. flecainide, metoprolol, imipramine, amitriptyline, clomipramine).
- Current use of drugs that are known to prolong the QTc interval such as: antiarrhythmics of classes IA and III; neuroleptics and antidepressant agents; certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, imidazole, and triazole antifungal agents; certain non-sedating antihistaminics (terfenadine, astemizole); cisapride.
- Disturbances of electrolyte balance, e.g. hypokalaemia.
- Inability to consume food
- Use of immunoglobulin or blood products within 3 months prior to enrolment.
- Participation in any other clinical study in the 30 days prior to the start of the study or during the study period, or prior receipt of an investigational malaria vaccine.
- Any other condition or situation that would, in the opinion of the investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.
- Any other significant disease, disorder or finding which may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study or impair interpretation of the study data.
Trial locations and contacts
1 site in 1 country.
About this study
Controlled human malaria infection (CHMI) is an important tool for the assessment of the efficacy of novel malaria vaccines and drugs prior to field trials. CHMI also allows for the evaluation of immunity to malaria and parasite growth rates in vivo and thus allows for the assessment of the natural acquisition and loss of malaria immunity. This may be particularly useful in individuals from endemic areas with changing levels of exposure and immunity to malaria. Thus, CHMI in individuals with prior exposure to malaria could be a valuable tool to accelerate malaria vaccine development and inform malaria control programs of changing immunity levels and related disease presentations. In this trial, the investigators intend to study the effect of pre-exposure to Plasmodium falciparum (Pf) on parasite kinetics, clinical symptoms and immunity after CHMI by PfSPZ Challenge in Gambian adults. Based on a well-defined sero-profile representing the extremes of current malaria exposure in The Gambia, two cohorts will be identified to study the impact of naturally acquired immunity on susceptibility for a Controlled Human Malaria Infection.
Read the detailed description
The main hypothesis is that cumulative exposure to natural Pf infections, as defined by the antibody profile to a defined panel of Pf antigens, is associated with an increasing pre-patent period and/or a reduced parasite growth rate in the CHMI after PfSPZ Challenge. The Primary objectives are to assess safety of PfSPZ Challenge administration in Gambian adults and to determine parasite kinetics in the CHMI model after PfSPZ Challenge in naturally exposed Gambian adults. The Secondary objective is to analyse humoral and cellular immune responses before and after CHMI in Gambian adults with different serological profiles to a panel of defined Pf-antigens.
The study is a single centre open-label clinical trial. The study population will be adult (aged 18 to 35 years) male, healthy subjects with at least 4 years of secondary school education. A total of 30 individuals will be enrolled to participate in the study; 15 with intense previous and recent exposure to malaria infections and 15 with very limited historic exposure to malaria and no evidence of recent malaria infections.
All participants will be checked for parasitaemia by qPCR before inclusion. Two subsequent negative qPCRs are needed before enrolment in the study to assure the absence of a P.falciparum infection. If one of the participants is not fit to participate in the study, another participant who fulfilled enrolment criteria will be included as replacement. For this purpose, two to four additional participants will be screened as back up. Subsequently, all participants will be subjected to a standard controlled human malaria infection (CHMI) by IV administration of a dose of 3.2 x 10^3 PfSPZ Challenge. After CHMI, participants will be closely followed with regular visits to the clinical trial centre (twice daily until day 15, and daily until day 28 or treatment) consisting of periodic physical examinations, frequent blood sampling and recording of adverse events in their diary. All relevant investigations will be carried out on an outpatient basis, including frequent safety analyses.
Participants should have access to a mobile phone upon which they can be reached 24 hours per day and 7 days per week. As additional safety precaution, participants are required to stay in a hotel/hostel close to the study facility from day 5 post-infection until 3 days after treatment. This mandatory stay in a hotel/hostel is to ensure study participants can be observed at all times and have excellent access to the clinical team. All participants will be treated with a curative regimen of artemether-lumefantrine that radically clears asexual parasites and developing gametocytes. The criteria for treatment post-CHMI will include positive thick smear during follow-up, decision of the study clinician or the local safety monitor, on request of the participant or on day 28 post-CHMI. All participants will be checked for parasites by thick smear at least twice after treatment.
- Conditions
- Malaria
- Being tested
- PfSPZ Challenge
- Keywords
- malaria, infection, controlled
- Medical subject headings
- Malaria, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PfSPZ ChallengeOther
The administration of an injection PfSPZ Challenge in Gambian adults
| Study group | Role | What they receive |
|---|---|---|
| PfSPZ Challenge | Other | this is a basic sciences protocol designed to study the effect of pre-exposure to Plasmodium falciparum (Pf) on malaria parasite kinetics, clinical symptoms and immunity after Controlled Human Malaria Infection by administration of an injection PfSPZ Challenge in Gambian adults. Based on a well-defined serological profile representing the extremes of current malaria exposure in The Gambia, two cohorts will be identified to study the impact of naturally acquired immunity on susceptibility for a Controlled Human Malaria Infection. The classification as a clinical trial results from the administration of the PfSPZ Challenge to the healthy volunteers Receives: Other: PfSPZ Challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
frequency and magnitude of adverse events
Frequency, incidence, nature and magnitude of adverse events
Measured: 28 days
time to first detection of parasites and parasites density
to compare time to first detection of parasites and parasite density at first detection by 18S qPCR and varATS qPCR. This time to patency and first parasite density are important indicators of pre-erythrocytic immunity and will be compared between cohorts A and B
Measured: 28 days
Secondary outcomes (3)
Time to Pf-NF54 parasitemia
Time to Pf-NF54 parasitemia after CHMI as assessed by qPCR
Measured: 28 days
parasite growth
Dynamics of Pf-NF54 parasite growth from day 5 after CHMI until day 28 as assessed by qPCR
Measured: day 5 to day 28
differences in immune responses
Intra and inter-group differences in cellular and humoral immune responses
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 posted12 Apr 2018
- Study start29 Mar 2018
- Primary completion3 May 2018
- Study completion5 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center, Sanaria Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03496454
- Sponsor's protocol ID
- SCC 1529
- Acronym
- CHMI-Gambia1
- Status last verified
- Jan 2019
- First submitted
- 29 Mar 2018
- Last updated
- 16 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Achan J, Reuling IJ, Yap XZ, Dabira E, Ahmad A, Cox M, Nwakanma D, Tetteh K, Wu L, Bastiaens GJH, Abebe Y, Manoj A, Kaur H, Miura K, Long C, Billingsley PF, Sim BKL, Hoffman SL, Drakeley C, Bousema T, D'Alessandro U. Serologic Markers of Previous Malaria Exposure and Functional Antibodies Inhibiting Parasite Growth Are Associated With Parasite Kinetics Following a Plasmodium falciparum Controlled Human Infection. Clin Infect Dis. 2020 Jun 10;70(12):2544-2552. doi: 10.1093/cid/ciz740.
PubMed 31402382
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Susceptibility of Gambian Adults to PfSPZ-Challenge Infection in the Controlled Human Malaria Infection Model
- ClinicalTrials.gov ID
- NCT03496454
- Acronym / sponsor ID
- CHMI-Gambia1 / SCC 1529
- Conditions
- Malaria
- Keywords
- malaria, infection, controlled
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- Radboud University Medical Center, Sanaria Inc.
- Study start
- 29 Mar 2018 (actual)
- Primary completion
- 3 May 2018 (actual)
- Study completion
- 5 Dec 2018 (actual)
- First posted
- 12 Apr 2018 (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.
Controlled human malaria infection (CHMI) is an important tool for the assessment of the efficacy of novel malaria vaccines and drugs prior to field trials. CHMI also allows for the evaluation of immunity to malaria and parasite growth rates in vivo and thus allows for the assessment of the natural acquisition and loss of malaria immunity. This may be particularly useful in individuals from endemic areas with changing levels of exposure and immunity to malaria. Thus, CHMI in individuals with prior exposure to malaria could be a valuable tool to accelerate malaria vaccine development and inform malaria control programs of changing immunity levels and related disease presentations. In this trial, the investigators intend to study the effect of pre-exposure to Plasmodium falciparum (Pf) on parasite kinetics, clinical symptoms and immunity after CHMI by PfSPZ Challenge in Gambian adults. Based on a well-defined sero-profile representing the extremes of current malaria exposure in The Gambia, two cohorts will be identified to study the impact of naturally acquired immunity on susceptibility for a Controlled Human Malaria Infection.
Detailed description
The main hypothesis is that cumulative exposure to natural Pf infections, as defined by the antibody profile to a defined panel of Pf antigens, is associated with an increasing pre-patent period and/or a reduced parasite growth rate in the CHMI after PfSPZ Challenge. The Primary objectives are to assess safety of PfSPZ Challenge administration in Gambian adults and to determine parasite kinetics in the CHMI model after PfSPZ Challenge in naturally exposed Gambian adults. The Secondary objective is to analyse humoral and cellular immune responses before and after CHMI in Gambian adults with different serological profiles to a panel of defined Pf-antigens.
The study is a single centre open-label clinical trial. The study population will be adult (aged 18 to 35 years) male, healthy subjects with at least 4 years of secondary school education. A total of 30 individuals will be enrolled to participate in the study; 15 with intense previous and recent exposure to malaria infections and 15 with very limited historic exposure to malaria and no evidence of recent malaria infections.
All participants will be checked for parasitaemia by qPCR before inclusion. Two subsequent negative qPCRs are needed before enrolment in the study to assure the absence of a P.falciparum infection. If one of the participants is not fit to participate in the study, another participant who fulfilled enrolment criteria will be included as replacement. For this purpose, two to four additional participants will be screened as back up. Subsequently, all participants will be subjected to a standard controlled human malaria infection (CHMI) by IV administration of a dose of 3.2 x 10^3 PfSPZ Challenge. After CHMI, participants will be closely followed with regular visits to the clinical trial centre (twice daily until day 15, and daily until day 28 or treatment) consisting of periodic physical examinations, frequent blood sampling and recording of adverse events in their diary. All relevant investigations will be carried out on an outpatient basis, including frequent safety analyses.
Participants should have access to a mobile phone upon which they can be reached 24 hours per day and 7 days per week. As additional safety precaution, participants are required to stay in a hotel/hostel close to the study facility from day 5 post-infection until 3 days after treatment. This mandatory stay in a hotel/hostel is to ensure study participants can be observed at all times and have excellent access to the clinical team. All participants will be treated with a curative regimen of artemether-lumefantrine that radically clears asexual parasites and developing gametocytes. The criteria for treatment post-CHMI will include positive thick smear during follow-up, decision of the study clinician or the local safety monitor, on request of the participant or on day 28 post-CHMI. All participants will be checked for parasites by thick smear at least twice after treatment.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PfSPZ Challenge | Other | Other: PfSPZ Challengethis is a basic sciences protocol designed to study the effect of pre-exposure to Plasmodium falciparum (Pf) on malaria parasite kinetics, clinical symptoms and immunity after Controlled Human Malaria Infection by administration of an injection PfSPZ Challenge in Gambian adults. Based on a well-defined serological profile representing the extremes of current malaria exposure in The Gambia, two cohorts will be identified to study the impact of naturally acquired immunity on susceptibility for a Controlled Human Malaria Infection. The classification as a clinical trial results from the administration of the PfSPZ Challenge to the healthy volunteers |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Males aged ≥ 18 and ≤ 35 years and in good health;
- At least 4 completed years of secondary education;
- Adequate understanding of the procedures of the study in English language;
- Willing (in the investigator's opinion) to comply with all study requirements;
- Willing to complete an informed consent questionnaire and is able to answer all questions correctly;
Key exclusion criteria (23 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, renal, hepatic, neurological, dermatological, endocrine,malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the participant during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following
- qPCR positive for Pf parasites at screening or previous participation in any malaria (vaccine) study.
- Known hypersensitivity to artemether-lumefantrine.
- Current use of any drug that is metabolised by the cytochrome enzyme CYP2D6 (e.g. flecainide, metoprolol, imipramine, amitriptyline, clomipramine).
- Current use of drugs that are known to prolong the QTc interval such as: antiarrhythmics of classes IA and III; neuroleptics and antidepressant agents; certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, imidazole, and triazole antifungal agents; certain non-sedating antihistaminics (terfenadine, astemizole); cisapride.
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 |
|---|---|---|
| PfSPZ ChallengeThe administration of an injection PfSPZ Challenge in Gambian adults | Other | PfSPZ Challenge |
Primary outcome
frequency and magnitude of adverse events
Time frame: 28 days
Frequency, incidence, nature and magnitude of adverse events
time to first detection of parasites and parasites density
Time frame: 28 days
to compare time to first detection of parasites and parasite density at first detection by 18S qPCR and varATS qPCR. This time to patency and first parasite density are important indicators of pre-erythrocytic immunity and will be compared between cohorts A and B
3 secondary outcomes
Time to Pf-NF54 parasitemia
Time frame: 28 days
parasite growth
Time frame: day 5 to day 28
differences in immune responses
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 16 Jan 2019.
- Derived from this study: PubMed 31402382Achan J, Reuling IJ, Yap XZ, Dabira E, Ahmad A, Cox M, Nwakanma D, Tetteh K, Wu L, Bastiaens GJH, Abebe Y, Manoj A, Kaur H, Miura K, Long C, Billingsley PF, Sim BKL, Hoffman SL, Drakeley C, Bousema T, D'Alessandro U. Serologic Markers of Previous Malaria Exposure and Functional Antibodies Inhibiting Parasite Growth Are Associated With Parasite Kinetics Following a Plasmodium falciparum Controlled Human Infection. Clin Infect Dis. 2020 Jun 10;70(12):2544-2552. doi: 10.1093/cid/ciz740.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PfSPZ Challenge in people with Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
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 13 inclusion and 23 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 16 Jan 2019. 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 The Gambia. 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?
frequency and magnitude of adverse events (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03496454, which also lists 1 linked publication.
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 16 Jan 2019.