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Malaria,FalciparumEarly Phase 1CoGANCT05468606

Coadministration of GA2 Sporozoites With Adjuvants

A Early Phase 1 study testing GA2, BCG and YF-17D (fractional ID dose) in people with Malaria,Falciparum, run by Leiden University Medical Center at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study will assess the coadministration of genetically attenuated Plasmodium falciparum ∆mei2 (GA2) sporozoites with adjuvants (BCG and YF-17D vaccination and imiquimod cream). Primary outcomes will be safety, tolerability and protective efficacy against CHMI. 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?
GA2, BCG and YF-17D (fractional ID dose)
Type of treatment
Vaccines
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
45 participants
Where
1 siteNetherlands
Study dates
3 Feb 2023to Dec 2024
Phase
Early Phase 1
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
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Participant is aged ≥18 and ≤35 years and in good health.
  • 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.
  • Participant agrees to refrain from blood donation to the national blood bank or for other purposes throughout the study period and for a defined period thereafter according to national blood bank guidelines.
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  • 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

  • 1. 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. f. 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 or adjuvants 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.
  • 2. For participants of child bearing potential: breastfeeding, or positive urine pregnancy test prior to immunization or prior to CHMI.
  • 3. Any history of malaria or previous participation in any malaria (vaccine) study or CHMI.
  • 4. 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.
  • 5. A history of severe (allergic) reactions to mosquito bites. 6. Any history of infection with mycobacteria or BCG vaccination (only in stage B and C) 7. Any history of infection with yellow fever virus or yellow fever vaccination (only in stage B and C).
  • 8. 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.
  • 9. Any condition or situation that could influence the independent consent of participant (e.g. being a direct colleague or family member of study personnel.
  • 10. 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

1 site in 1 country.

Meta Roestenberg, MD, PhD contact

+31715262102

M.Roestenberg@lumc.nl

Netherlands1 site, 1 recruiting
  • Leiden University Medical Center

    Leiden, 2333 ZA

    M. Roestenberg, MD. PhD.

    M. Roestenberg, MD. PhD.

    Recruiting

Other trials in Netherlands

About this study

Official title: Coadministration of Genetically Attenuated Plasmodium Falciparum ∆mei2 (GA2) Sporozoites With Adjuvants - a Proof of Principle Study

This study will assess the coadministration of genetically attenuated Plasmodium falciparum ∆mei2 (GA2) sporozoites with adjuvants (BCG and YF-17D vaccination and imiquimod cream). Primary outcomes will be safety, tolerability and protective efficacy against CHMI.

Read the detailed description

This will be an adaptive design single center, randomized controlled partly blinded, partly open-label clinical proof-of-principle trial of the genetically attenuated parasite GA2 co-administered with adjuvants in healthy, malaria-naïve male and female participants with no prior history of BCG or YF-17D vaccination. A total of 45 participants will be immunized by the bites of 50 GA2 infected mosquitos. Additionally, ten participants will serve as infectivity controls and will be exposed to the bites of 50 uninfected mosquitoes in the immunization phase.

During the 42 days following the immunization, there will be four out-patient visits and one phone call visit to evaluate adverse events and for hematology, biochemistry and immunology laboratory assessment. Six weeks after immunization, all 45 participants will undergo a 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 parasitemia is detected (cut-off >100p/mL), or at the latest 28 days after CHMI, participants will be treated with a curative regimen of antimalarials. The trial will be held in two cohorts: the second cohort starting 4 weeks after the first. The first cohort will consist of 10 participants and the second cohort will consist of 15 participants. Both cohorts will be block randomized to the five different study groups.

The study will consist of three stages. In stage A of the study, ten GA2 immunized participants will be compared to five infectivity controls in a blinded design. If the protective efficacy of the GA2 immunized group is ≤7/10 and some efficacy is seen in stage A (either ≥10% protection or significant increase in time to parasitemia) then the study will progress to stage B. In this stage, BCG (n=5), YF-17D (n=5) or imiquimod (n=5) will be applied/administered to the GA2 administration site. Additionally, two infectivity controls will participate in stage B. Stage B will be open label.

Based on the data on safety, tolerability and immunogenicity, the most favorable adjuvant of stage B can be chosen to be further assessed in stage C. In stage C, additional participants will be immunized with 50 GA2 infected mosquitoes in combination with the selected adjuvant. Additionally, a group of five unadjuvanted GA2 immunized participants and three infectivity controls will participate. The adjuvanted group of stage C will be open-label, the unadjuvanted group and the infectivity controls will be blinded.

Being tested
GA2, BCG, YF-17D (fractional ID dose), Imiquimod, Mock immunization
Medical subject headings
Malaria, Falciparum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GA2Biological

    GA2 sporozoites administered by 50 mosquito bites

  • BCGBiological

    0.1 mL BCG vaccine intradermally

  • YF-17D (fractional ID dose)Biological

    Also called Stamaril

    0.1 mL YF17D vaccine intradermally

  • ImiquimodDrug

    Also called Aldara

    250mg imiquimod 5% cream topical

  • Mock immunizationOther

    50 bites by uninfected mosquitoes

Study groups in NCT05468606
Study groupRoleWhat they receive
GA2 group (unadjuvanted group)ExperimentalImmunization with 50 GA2-infected mosquito bites
Receives: Biological: GA2
Infectivity controls (placebo group)Placebo comparatorMock-immunization with 50 uninfected-mosquito bites
Receives: Other: Mock immunization
BCG groupExperimentalImmunization with 50 GA2-infected mosquito bites and a standard intradermal BCG vaccination (0.1 mL)
Receives: Biological: GA2; Biological: BCG
YF-17D groupExperimentalImmunization with 50 GA2-infected mosquito bites and a one fifth fractional (0.1 mL) intradermal YF-17D vaccination
Receives: Biological: GA2; Biological: YF-17D (fractional ID dose)
Imiquimod groupExperimentalImmunization with 50 GA2-infected mosquito bites and 250mg imiquimod cream 5%
Receives: Biological: GA2; Drug: Imiquimod

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to parasitemia

    The time to parasitemia (qPCR >100p/mL) (prepatent period) after CHMI in participants immunized with the GA2 parasite co-administered with an adjuvant compared to the unadjuvanted group and the infectivity controls.

    Measured: Moment of CHMI to antimalarial treatment (28 days post CHMI)

  2. Safety and tolerability: frequency and magnitude of adverse events in all study groups.

    The number of graded adverse events occurring in each group will be calculated as absolute numbers. Frequencies will be calculated by dividing the number of graded adverse events occurring in each group by the total number of volunteers in each group

    Measured: Moment of immunization to 35 days post CHMI

  3. Protective efficacy

    Proportion of participants immunized with the GA2 parasite co-administered with an adjuvant that do not develop parasitemia (qPCR >100p/mL) (sterile protection) after CHMI comparted the unadjuvanted group and the infectivity controls.

    Measured: Moment of CHMI to antimalarial treatment (28 days post CHMI)

Secondary outcomes (1)
  1. Humoral immune responses of volunteers exposed to different intervention arms

    Difference in concentration of anti-CSP antibodies between intervention arms as assessed by ELISA.

    Measured: Moment of immunization, pre-CHMI and up to 182 days post CHMI

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2022
  2. Study start3 Feb 2023
  3. Primary completionDec 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Sequential
Model description
The study will consist of three stages (A, B, C). In stage A of the study, ten GA2 immunized participants will be compared to five infectivity controls in a blinded design. If the protective efficacy of the GA2 immunized group is ≤7/10 and some efficacy is seen in stage A (either ≥10% protection or significant increase in time to parasitemia) then the study will progress to stage B. In this stage, BCG (n=5), YF-17D (n=5) or imiquimod (n=5) will be applied/administered to the GA2 administration site. Additionally, two infectivity controls will participate in stage B. Based on the data on safety, tolerability and immunogenicity, the most favorable adjuvant of stage B can be chosen to be further assessed in stage C. In stage C, additional participants will be immunized with 50 GA2 infected mosquitoes in combination with the selected adjuvant. Additionally, a group of five unadjuvanted GA2 immunized participants and three infectivity controls will participate.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05468606
Sponsor's protocol ID
CoGA
Acronym
CoGA
Status last verified
Feb 2023
First submitted
14 Jul 2022
Last updated
10 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Roozen GVT, van Schuijlenburg R, Hensen ADO, Koopman JPR, Lamers OAC, Geurten FJA, Sijtsma JC, Baalbergen E, Janse JJ, Chevalley-Maurel S, Naar CM, Bezemer S, Kroeze H, van de Stadt HJF, de Visser B, Meij P, Tihaya MS, Colstrup E, Iliopoulou E, de Bes-Roeleveld HM, Wessels E, van der Stoep MYEC, Janse CJ, Murugan R, Franke-Fayard BMD, Roestenberg M. Single immunization with genetically attenuated Pf∆mei2 (GA2) parasites by mosquito bite in controlled human malaria infection: a placebo-controlled randomized trial. Nat Med. 2025 Jan;31(1):218-222. doi: 10.1038/s41591-024-03347-2. Epub 2025 Jan 3.

    PubMed 39753962

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing GA2, BCG and YF-17D (fractional ID dose) in people with Malaria,Falciparum, run by Leiden University Medical Center at 1 site in Netherlands.

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 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: status not confirmed, as of the sponsor's last update on 10 Feb 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 Netherlands. 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. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Meta Roestenberg, MD, PhD (+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?

Time to parasitemia (time frame: Moment of CHMI to antimalarial treatment (28 days post CHMI)). The study lists 3 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 NCT05468606, 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 10 Feb 2023.

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