Durability of Protection After Single Immunisation With GA2 Sporozoites (CoGA-Rechallenge)

NCT06293339 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CoGA-Re
• Study Type: interventional
• Target: 14
• Locations: 0 countries
• Sites: N/A

Brief 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)

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

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

Secondary Outcomes (2)

• Humoral immune responses after homologous CHMI rechallenge

  Moment of CHMI up to182 days post CHMI

• Cellular immune responses after homologous CHMI rechallenge

  Moment of CHMI up to182 days post CHMI

Study Arms (2)

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)

Biological: CHMI with 3D7 malaria

Infection control group

PLACEBO COMPARATOR

Malaria-naïve participants who have not been previously vaccinated with GA2

Biological: CHMI with 3D7 malaria

Interventions

CHMI with 3D7 malaria BIOLOGICAL

Controlled human malaria infection with 3D7 malaria through mosquito bites

Infection control group; Rechallenge 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.
• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Leiden University Medical Center: lead

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

1-acetyl-1,2,3,3a,8,8a-hexahydro-8a-hydroxy-5-methoxypyrrolo(2,3-b)indole

Condition Hierarchy (Ancestors)

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

Study Officials

• Meta Roestenberg, Prof

  LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meta Roestenberg, Prof.

CONTACT

+31715262102; M.Roestenberg@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 5, 2024
• Study Start: March 1, 2025
• Primary Completion: July 1, 2025
• Study Completion: September 30, 2025
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share