A Phase 1 interventional study of Controlled Human Malaria Infection in Malaria (Plasmodium Falciparum), sponsored by Centre de Recherche Médicale de Lambaréné. Completed at 1 site in Gabon. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-11.
Sponsored by Centre de Recherche Médicale de Lambaréné · Phase 1, Interventional, and Other
The project aims to reproduce the malaria infection cycle using African mosquitoes, namely Anopheles gambiae and a local strain of Plasmodium parasites. The study will be conducted in two steps: (i) the production of infected mosquitoes and (ii) human infection with malaria parasites, known as Controlled Human Malaria Infection (CHMI). During the first step, Anopheles gambiae mosquitoes raised in the Centre de Recherches Médicales de Lambaréné (CERMEL) entomology laboratory in Lambaréné, Gabon, will be fed with blood collected from a person living in Lambaréné or the surrounding area who is positive for Plasmodium falciparum parasites, with the presence of asexual and sexual stages (responsible for malaria transmission) of the parasites in his/her blood. The Plasmodium-infected mosquitoes will be used two weeks later to infect healthy adult volunteers by mosquito bites under the supervision of the research team. After exposure, we will follow all exposed participants daily, starting on the fifth day after exposure. During the daily visits, we will perform malaria tests to detect the presence of malaria parasites in the blood of the participant. If participants test positive, they will receive usual antimalarial treatment if they simultaneously present malaria symptoms or if their parasitaemia is equal to or greater than 1,000 parasites per microlitre of blood. To ensure participants are effectively treated, we will perform two malaria tests after treatment, which should be negative. Otherwise, a different treatment will be administered. We will consider the process successful if we manage to infect (presence of malaria parasites in the blood) at least 50% of exposed participants. We also want the process to be safe, assuming that no unexpected clinical or biological events occur. Such an approach could contribute to a better assessment of the efficacy of antimalarial drugs and vaccine candidates, taking into account the specific characteristics of each endemic area.
Controlled Human Malaria Infection (CHMI) is a model to investigate immunity to malaria, diagnostics and, most importantly, antimalarial interventions. In the modern era, with the invention of parasite culture, it has almost exclusively used laboratory-adapted P. falciparum strains (NF54, 3D7, 7G8, NF135.C10, and NF166.C8) to infect volunteers either via injection of purified sporozoites or using infected mosquito bites ("flying syringes"). This model has greatly contributed to the evaluation of the efficacy of candidate antimalarial drugs or vaccines. However, one of its limitations lies in the fact that it does not take into consideration the genetic heterogeneity of Plasmodium infections typically presents in malaria-endemic regions. Indeed, P. falciparum strains in malaria-endemic regions are constantly under pressure from the host's human immune system and therapeutic interventions. This leads to genetically diverse strains of P. falciparum, different from the laboratory-adapted strains. Consequently, restricting CHMI to laboratory-adapted P. falciparum strains might not predict well the efficacy of vaccine candidates or antimalarial drugs in endemic settings, nor can it fully represent the biology of parasite field isolates and their potential interaction with hosts and other pathogens endemic in these areas. Therefore, it is postulated in this study that the CHMI model can be established in malaria-endemic regions using P. falciparum field isolates. This will not only contribute to the stringent evaluation of the efficacy of vaccine or antimalarial drug candidates in these settings but also to the understanding of the interaction between malaria and other diseases, particularly helminths.
The main objective of the present work is thus to establish a safe protocol for the controlled infection of healthy adult human volunteers in an endemic area with local strains of P. falciparum via bites of infected A. gambiae s.s. Primarily, we will assess the infectivity to healthy adult Gabonese volunteers of A. gambiae Kisumu strain mosquitoes infected with local isolates of Pf. In addition, we will assess the safety of this CHMI procedure using locally P. falciparum-infected A. gambiae mosquitoes
The project will be composed of two steps: the production of mosquitoes infected with P. falciparum (Clinical Trial Material) at the entomology laboratory of CERMEL following established SOPs, and CHMI by bites of Pf-infected mosquitoes on healthy volunteers. Pf-infected mosquitoes (abbreviated as Pf-iAgK mosquitoes) will be produced by infecting through membrane-feeding laboratory-raised A. gambiae Kisumu strain mosquitoes with a Pf gametocyte isolate obtained from a suitable donor. Consequently, only the successfully Pf-infected eligible batches of A. gambiae will be further used in the project. The CTM release criteria are:
The study will include twenty or thirty participants. First, ten healthy adult volunteers will be recruited to receive 5 Pf-infected mosquito bites each under direct supervision on day 0 (Cohort A1). If at least 50% of volunteers in Cohort A are found to be Pf-infected during the follow-up period, 10 more healthy adult volunteers will be enrolled to receive bites by the same number of Pf-infected A. gambiae mosquitoes using the same follow-up design as above (Cohort A2) but using a Pf isolate from one or more new donors. Data from Cohorts A1 and A2 will be combined to calculate infectivity rates. If less than 50% of volunteers in Cohort A1 are found to be Pf-infected during the follow-up, 10 more healthy adult volunteers will be enrolled to be bitten by double the number of Pf-infected A. gambiae mosquitoes (i.e., 10 mosquitoes) (Cohort B1) using Pf isolates from one or more new donors. If at least 50% of volunteers in Cohort B1 are found to be Pf-infected during the follow-up period, 10 more healthy adult volunteers will be enrolled to be bitten by the same number of Pf-infected A. gambiae mosquitoes (i.e., 10) (Cohort B2) but using Pf isolates from one or more new donors. Data from Cohorts B1 and B2 will then be combined to calculate infectivity rates. Further dose escalation (number of Pf-infected mosquito bites) may be considered via a potential amendment, depending on the safety and infectivity results in Cohort B1.
In the study procedure, the sporozoites of Pf isolates will be inoculated into recipients via bites of PfiAgK mosquitoes. Recipients will be exposed to bites of infected mosquitoes for 10 minutes. After exposure, the number of fed and unfed mosquitoes will be recorded. Fed mosquitoes will be dissected to confirm the presence of sporozoites in the salivary glands. Any fed mosquitoes without sporozoites in the salivary glands, along with unfed mosquitoes, will be replaced by an identical number of infected mosquitoes for another round of 10 minutes of exposure until the required number of infected mosquitoes with sporozoites successfully take blood from the recipient.
Each participant will be followed up for a period of 28 days, starting from day 5 post-exposure and qPCR (RT-qPCR based on 18S rRNA genes) and thick blood smear (TBS) will be performed to detect asexual blood stage parasitaemia. qPCR and TBS sampling will be performed daily until one of the malaria treatment criteria is met by day 28. Venous blood samples for immunology will be taken on days 0, 5, 11, 14, 28, and as applicable on the day of treatment before treatment administration. Venous blood samples will be taken for genetic and transcriptomic analyses on days 11, 14 and 28 or on the day of treatment before treatment administration.
455 studies on the registry are indexed under Malaria, Falciparum; 37 are open to participants now.
This study's enrollment of 20 is below the median of 126 across 376 interventional studies indexed under Malaria, Falciparum.
Browse Malaria, Falciparum studies →Centre de Recherche Médicale de Lambaréné is the lead sponsor of 17 studies on the registry; 3 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in this arm will receive Plasmodium falciparum-infected mosquito bites each under direct supervision
Biological: Controlled Human Malaria Infection
Anopheles gambiae mosquitoes infected with a local strain of Plasmodium falciparum will be used to perform a CHMI by mosquito bites in healthy adult volunteers
Number of participants with Asexual P. falciparum blood stage infection detected by qPCR
Time frame: Until 21 days post-exposure
Number and frequency of adverse events
The total number and frequency of adverse events (AEs) will be reported, along with the number by severity.
Time frame: During the 28-day follow-up period
Number of participants with asexual P. falciparum blood stage infection detected by qPCR
Time frame: Until 28 days post-exposure
Number of symptoms consistent with Plasmodium falciparum malaria
The list and frequency of symptoms consistent with Plasmodium falciparum malaria will be provided
Time frame: During the 28-day follow-up period
Ran from Jul 2025 to primary completion in Feb 2026, 7 months.
Of 29 non-industry phase 1 interventional studies under Malaria, Falciparum, half reached primary completion within 12 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 24. This study's 7 months is below that.
Counting every sponsor, half of 49 studies reached it within 13 months; a quarter within 7 and three quarters within 18.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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Centre de Recherche Médicale de Lambaréné