Malaria,FalciparumPhase 1NCT06293339
Durability of Protection After Single Immunisation With GA2 Sporozoites (CoGA-Rechallenge)
A Phase 1 study testing CHMI with 3D7 malaria in people with Malaria,Falciparum, run by Leiden University Medical Center.
Trial summary
This study will assess the durability of protection of a single immunisation with the Genetically Attenuated Parasite 2 (GA2) against controlled human malaria infection by rechallenging previously immunised and protected participants from the CoGA study (NCT05468606) Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria,Falciparum
- What is being tested?
- CHMI with 3D7 malaria
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2025to 30 Sep 2025
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participant is aged ≥18 and ≤35 years and in good health.
- Rechallenge group only: participation in CoGA study, having received immunisation with 1x 50 GA2-infected MB, and protected during subsequent CHMI.
- Participant has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
- Participant is able to communicate well with the investigator.
- Participant is available to attend all essential study visits.
- Participant agrees that his/her general practitioner (GP) will be informed about participation in the study.
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- Participant agrees to refrain from blood donation to Sanquin or for other purposes. throughout the study period and for a defined period thereafter according to Sanquin guidelines.
- Participants of child bearing potential (i.e., have an uterus and are neither surgically sterilized nor post-menopausal) agree to use adequate contraception and to not breastfeed for the duration of study.
- Participant agrees to refrain from intensive physical exercise (disproportionate to the participants' usual daily activity or exercise routine) for twenty-one days following the immunization and during the malaria challenge period.
- Participant signs informed consent.
Who cannot join
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions 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 Mass Index (BMI) >35.0 kg/m2 at screening. b. An elevated risk of cardiovascular disease, defined as: i. An estimated ten-year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation 2 (SCORE2) .
- History, or evidence at screening, of clinically significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG abnormalities; or iii. A positive family history of cardiac events in first- or second-degree relatives (according to the system used in medical genetics) <50 years old.
- Known functional asplenia, sickle cell trait/disease, thalassemia trait/disease or G6PD deficiency.
- History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
- Positive HIV, HBV or HCV screening tests. e. Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other drugs that might have an influence on the immune system (excluding inhaled and topical corticosteroids and incidental use of oral anti-histamines), within three months prior to study onset or expected use of such during the study period.
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- Skin disease affecting the site of administration in such a way that administration of mosquito bites is deemed impossible by investigator.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past five 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 functioning in the period of one year prior to study onset, positive urine toxicology test for cocaine or amphetamines at screening.
- For participants of child bearing potential: breastfeeding, or positive serum pregnancy test prior to CHMI.
- Infection controls only: any history of malaria or previous participation in any malaria (vaccine) study or CHMI.
- Known hypersensitivity to or contra-indications for both atovaquone/proguanil or artemether/lumefantrine. QT prolonging drugs are only considered an exclusion criterion when QT prolongation is observed at the ECG at screening.
- A history of severe (allergic) reactions to mosquito bites.
- Participation in any other clinical study assessing an investigational medical product in the 30 days prior to the start of the study or during the study period.
- Any condition or situation that could influence the independent consent of participant (e.g. being a direct colleague or family member of study personnel).
- 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 or would compromise the integrity of the data.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Durability of Protection After Single Immunisation With Genetically Attenuated Plasmodium Falciparum ∆mei2 (GA2) Sporozoites - a Follow-up, Controlled Human Malaria Rechallenge Study
This study will assess the durability of protection of a single immunisation with the Genetically Attenuated Parasite 2 (GA2) against controlled human malaria infection by rechallenging previously immunised and protected participants from the CoGA study (NCT05468606)
Read the detailed description
This will be a non-randomised, open-label, controlled human malaria infection study that will consist of two study arms: the rechallenge group and infection controls. The rechallenge group consists of study participants from the CoGA study (phase I) who received single immunisation with GA2 and were protected during subsequent CHMI, while infection controls are newly recruited, malaria-naïve study participants. All participants will undergo CHMI through the bites of 5 mosquitos infected with wild-type 3D7 sporozoites. From day 6 to 21 after CHMI, participants will be followed daily on an out-patient basis to determine parasite loads detected by a quantitative polymerase chain reaction (qPCR). As soon as parasitaemia is detected (cut-off >100p/mL), or at the latest 28 days after CHMI, participants will be treated with a curative regimen of antimalarials.
- Conditions
- Malaria,Falciparum
- Being tested
- CHMI with 3D7 malaria
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHMI with 3D7 malariaBiological
Controlled human malaria infection with 3D7 malaria through mosquito bites
| Study group | Role | What they receive |
|---|---|---|
| Rechallenge group | Experimental | Previous CoGA phase 1 study participants who were immunised with GA2 and who did not develop blood-stage malaria during CHMI (protected) Receives: Biological: CHMI with 3D7 malaria |
| Infection control group | Placebo comparator | Malaria-naïve participants who have not been previously vaccinated with GA2 Receives: Biological: CHMI with 3D7 malaria |
What is being measured
The primary outcome is the main question the study is designed to answer.
Protective efficacy
Proportion of participants that do not develop parasitaemia (qPCR >100p/mL) (sterile protection) after CHMI (re)challenge in participants with prior, single GA2 immunisation compared to infection controls.
Measured: Moment of CHMI to antimalarial treatment (28 days post CHMI)
Time to parasitaemia
The time to parasitaemia (qPCR >100 p/mL) (prepatent period) after CHMI (re)challenge between participants with prior, single GA2 immunisation and infection controls.
Measured: Moment of CHMI to antimalarial treatment (28 days post CHMI)
Secondary outcomes (2)
Humoral immune responses after homologous CHMI rechallenge
Difference in concentration of anti-CSP antibodies between groups as assessed by ELISA.
Measured: Moment of CHMI up to182 days post CHMI
Cellular immune responses after homologous CHMI rechallenge
Difference in percentage of CD4+ and CD8+ T-cells producing IFN-γ between groups as assessed by flow cytometry
Measured: Moment of CHMI up to182 days post CHMI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2024
- Study start1 Mar 2025 (estimated)
- Primary completion1 Jul 2025 (estimated)
- Study completion30 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malaria,FalciparumStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe 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 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meta Roestenberg, Leiden University Medical Center
- Investigators
- Meta Roestenberg, Prof, Principal investigator, LUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06293339
- Sponsor's protocol ID
- CoGA-Re
- Status last verified
- Dec 2024
- First submitted
- 27 Feb 2024
- Last updated
- 27 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Durability of Protection After Single Immunisation With Genetically Attenuated Plasmodium Falciparum ∆mei2 (GA2) Sporozoites - a Follow-up, Controlled Human Malaria Rechallenge Study
- ClinicalTrials.gov ID
- NCT06293339
- Acronym / sponsor ID
- CoGA-Re
- Conditions
- Malaria,Falciparum
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2025 (estimated)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 5 Mar 2024 (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 study will assess the durability of protection of a single immunisation with the Genetically Attenuated Parasite 2 (GA2) against controlled human malaria infection by rechallenging previously immunised and protected participants from the CoGA study (NCT05468606)
Detailed description
This will be a non-randomised, open-label, controlled human malaria infection study that will consist of two study arms: the rechallenge group and infection controls. The rechallenge group consists of study participants from the CoGA study (phase I) who received single immunisation with GA2 and were protected during subsequent CHMI, while infection controls are newly recruited, malaria-naïve study participants. All participants will undergo CHMI through the bites of 5 mosquitos infected with wild-type 3D7 sporozoites. From day 6 to 21 after CHMI, participants will be followed daily on an out-patient basis to determine parasite loads detected by a quantitative polymerase chain reaction (qPCR). As soon as parasitaemia is detected (cut-off >100p/mL), or at the latest 28 days after CHMI, participants will be treated with a curative regimen of antimalarials.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rechallenge group | Experimental | Biological: CHMI with 3D7 malariaPrevious CoGA phase 1 study participants who were immunised with GA2 and who did not develop blood-stage malaria during CHMI (protected) |
| Infection control group | Placebo comparator | Biological: CHMI with 3D7 malariaMalaria-naïve participants who have not been previously vaccinated with GA2 |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Participant is aged ≥18 and ≤35 years and in good health.
- Rechallenge group only: participation in CoGA study, having received immunisation with 1x 50 GA2-infected MB, and protected during subsequent CHMI.
- Participant has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
- Participant is able to communicate well with the investigator.
- Participant is available to attend all essential study visits.
Key exclusion criteria (17 listed)
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions 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:
- For participants of child bearing potential: breastfeeding, or positive serum pregnancy test prior to CHMI.
- Infection controls only: any history of malaria or previous participation in any malaria (vaccine) study or CHMI.
- Known hypersensitivity to or contra-indications for both atovaquone/proguanil or artemether/lumefantrine. QT prolonging drugs are only considered an exclusion criterion when QT prolongation is observed at the ECG at screening.
- A history of severe (allergic) reactions to mosquito bites.
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 |
|---|---|---|
| CHMI with 3D7 malariaControlled human malaria infection with 3D7 malaria through mosquito bites | Biological | Infection control group, Rechallenge group |
Primary outcome
Protective efficacy
Time frame: Moment of CHMI to antimalarial treatment (28 days post CHMI)
Proportion of participants that do not develop parasitaemia (qPCR >100p/mL) (sterile protection) after CHMI (re)challenge in participants with prior, single GA2 immunisation compared to infection controls.
Time to parasitaemia
Time frame: Moment of CHMI to antimalarial treatment (28 days post CHMI)
The time to parasitaemia (qPCR >100 p/mL) (prepatent period) after CHMI (re)challenge between participants with prior, single GA2 immunisation and infection controls.
2 secondary outcomes
Humoral immune responses after homologous CHMI rechallenge
Time frame: Moment of CHMI up to182 days post CHMI
Cellular immune responses after homologous CHMI rechallenge
Time frame: Moment of CHMI up to182 days post CHMI
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Individual participant dataSharing planned: No
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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.
Meta Roestenberg, Prof principal investigator
LUMC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CHMI with 3D7 malaria in people with Malaria,Falciparum, run by Leiden University Medical Center.
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 10 inclusion and 17 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: opening soon, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Meta Roestenberg, Prof. (+31715262102, M.Roestenberg@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Protective efficacy (time frame: Moment of CHMI to antimalarial treatment (28 days post CHMI)). 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?
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 27 Dec 2024.