Coadministration of GA2 Sporozoites With Adjuvants

NCT05468606 | Unknown Early Phase 1 DMC

• 1 other identifier: CoGA
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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

  Moment of immunization to 35 days post CHMI

• 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.

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

Secondary Outcomes (1)

• Humoral immune responses of volunteers exposed to different intervention arms

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

Other Outcomes (1)

• Cellular immune responses of volunteers exposed to different intervention arms

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

Study Arms (5)

GA2 group (unadjuvanted group)

EXPERIMENTAL

Immunization with 50 GA2-infected mosquito bites

Biological: GA2

Infectivity controls (placebo group)

PLACEBO COMPARATOR

Mock-immunization with 50 uninfected-mosquito bites

Other: Mock immunization

BCG group

EXPERIMENTAL

Immunization with 50 GA2-infected mosquito bites and a standard intradermal BCG vaccination (0.1 mL)

Biological: GA2; Biological: BCG

YF-17D group

EXPERIMENTAL

Immunization with 50 GA2-infected mosquito bites and a one fifth fractional (0.1 mL) intradermal YF-17D vaccination

Biological: GA2; Biological: YF-17D (fractional ID dose)

Imiquimod group

EXPERIMENTAL

Immunization with 50 GA2-infected mosquito bites and 250mg imiquimod cream 5%

Biological: GA2; Drug: Imiquimod

Interventions

GA2 BIOLOGICAL

GA2 sporozoites administered by 50 mosquito bites

BCG group; GA2 group (unadjuvanted group); Imiquimod group; YF-17D group

BCG BIOLOGICAL

0.1 mL BCG vaccine intradermally

BCG group

YF-17D (fractional ID dose) BIOLOGICAL

0.1 mL YF17D vaccine intradermally

Also known as: Stamaril

YF-17D group

Imiquimod DRUG

250mg imiquimod 5% cream topical

Also known as: Aldara

Imiquimod group

Mock immunization OTHER

50 bites by uninfected mosquitoes

Infectivity controls (placebo group)

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• \- 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:
• a. 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) .
• ii. 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.
• c. Known functional asplenia, sickle cell trait/disease, thalassemia trait/disease or G6PD deficiency.
• d. History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
• e. 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.
• g. Skin disease affecting the site of administration in such a way that administration of mosquito bites or adjuvants is deemed impossible by investigator.
• h. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past five years.
• i. Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
• j. 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 urine pregnancy test prior to immunization or prior to CHMI.
• \. Any history of malaria or previous participation in any malaria (vaccine) study or CHMI.
• \. 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).
• \. 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 39753962 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Meta Roestenberg, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meta Roestenberg, MD, PhD

CONTACT

+31715262102; M.Roestenberg@lumc.nl

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Stage A will be randomized and double blind. Stage B will be open-label. The adjuvanted group of stage C will be open-label, the unadjuvanted group and the infectivity controls will be blinded.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: 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.

Study Record Dates

• First Submitted: July 14, 2022
• First Posted: July 21, 2022
• Study Start: February 3, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 10, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)