Safety and Preliminary Protective Efficacy of Genetically Attenuated GA2 Parasites.

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-27

Study Completion Date

2022-12-22

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study will consist of two phases and be aimed at assessing the safety and tolerability of the new genetically attenuated GA2 malaria parasite (Phase 1) and its preliminary protective efficacy against controlled human malaria infection (Phase 2) in healthy Dutch volunteers.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Controlled Human Malaria Infection Model for Evaluation of Transmission-blocking Interventions - Study 2

NCT03454048

Malaria,Falciparum Gametocytes Controlled Human Malaria Infection +1 more

COMPLETED NA

Controlled Human Malaria Infection Model for Evaluation of Transmission-Blocking Interventions - Study 1

NCT02836002

Malaria

COMPLETED PHASE1/PHASE2

Phase 2 Efficacy Study of Primaquine and Methylene Blue

NCT02831023

Malaria

COMPLETED PHASE2

Controlled Human Malaria Infection After Bites From Mosquitoes Infected With Two Novel P. Falciparum Strains

NCT02149550

Malaria

COMPLETED NA

Genetic Association Mapping of Malaria Resistance in Anopheles Gambiae

NCT00850655

Malaria

COMPLETED

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Malaria is one of the most common tropical diseases, accounting for 228 million infections and 450.000 deaths each year. It is caused by five species of protozoan parasites belonging to the genus of the Plasmodia. Plasmodia have a complex life cycle: they are injected into the human host by female Anopheles mosquitos, migrate to the liver to replicate and then enter red blood cells. The typical symptoms of malaria with fever episodes are caused by the bursting of red blood cells, as the parasites leave to infect new cells.

The rising resistance of both parasites against anti-malarial drugs and mosquitoes against insecticides, make the need to eradicate malaria even more impellent. A promising approach to disease control is the development of an effective vaccine. Among the different approaches to vaccine development, live attenuated parasites stand out for their high protective efficacy (\>90%).

The GA2 parasite, a new genetically attenuated malaria parasite, which is derived from the NF45 Plasmodium falciparum strain and has been engineered to arrest development in the liver before entering the bloodstream, was recently created. It should therefore not be able to cause malaria in humans. The idea is that the GA2 parasite will prime the immune system for recognition of non attenuated parasites in the future without causing disease itself. In other words, exposure to the innocuous GA2 parasite could confer protection against pathogenic malaria parasites.

Hence, this study is aimed at investigating the safety and tolerability of the GA2 parasite and at determining its potential protective efficacy against controlled human malaria infection. The former question will be investigated by exposing volunteers to sequentially increasing numbers of GA2-infected mosquito bites. The latter question will be investigated by repeatedly (3 times) exposing volunteers to the GA2 parasite and once to unattenuated parasites. The efficacy of the GA2 parasite will be compared to another genetically attenuated parasite, the GA1, which in previous studies has been shown to be safe and well-tolerated but only have limited protective efficacy. There will also be a placebo group.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Plasmodium Falciparum Malaria

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This trial has both a sequential as well as a parallel interventional study model.

The safety and tolerability of the GA2 parasite will be assessed in phase 1 by means of a sequential study model. There will be 2 cohorts, which will be recruited sequentially and exposed to increasing numbers of infected mosquito bites.

The preliminary protective efficacy of the GA2 parasite will be assessed in phase 2 by means of a parallel study model. There will be 3 groups of volunteers, who will be exposed to either GA2-infected, GA1-infected or uninfected mosquito bites.

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Phase 1 will be an open label trial, Phase 2 will be a double-blind trial.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Group 1 (GA2)

Volunteers will be exposed to GA2-infected mosquito bites.

Group Type EXPERIMENTAL

GA2

Intervention Type OTHER

15 volunteers will receive 50 GA2-infected mosquito bites. The GA2 parasite is a new genetically attenuated Plasmodium falciparum parasite, which arrests development in the liver and should not be able to cause malaria in humans.

Group 2 (GA1)

Volunteers will be exposed to the GA1-infected mosquito bites.

Group Type ACTIVE_COMPARATOR

GA1

Intervention Type OTHER

10 volunteers will receive 50 GA1-infected mosquito bites. The GA1 parasite is a genetically attenuated Plasmodium falciparum parasite, which arrests development in the liver and is not able to cause malaria in humans.

Group 3 (Placebo)

Volunteers will be exposed to uninfected mosquito bites.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

5 volunteers will receive 50 uninfected mosquito bites.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

GA2

15 volunteers will receive 50 GA2-infected mosquito bites. The GA2 parasite is a new genetically attenuated Plasmodium falciparum parasite, which arrests development in the liver and should not be able to cause malaria in humans.

Intervention Type OTHER

GA1

10 volunteers will receive 50 GA1-infected mosquito bites. The GA1 parasite is a genetically attenuated Plasmodium falciparum parasite, which arrests development in the liver and is not able to cause malaria in humans.

Intervention Type OTHER

Placebo

5 volunteers will receive 50 uninfected mosquito bites.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Subject is aged ≥ 18 and ≤ 35 years and in good health.
* Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
* Subject is able to communicate well with the investigator, is available to attend all study visits.
* Furthermore, the subject will remain within the Netherlands from day -1 till day +28 after each parasite exposure. After CHMI, subjects have to be reachable by phone (24/7) from day -1 until day 35.
* Subject agrees to inform his/her general practitioner (GP) about participation in the study.
* Subject 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.
* Non-pregnant, non-lactating females of reproductive potential (i.e., have a uterus and are neither surgically sterilized nor post-menopausal) agree to use adequate contraception and to not breastfeed for the duration of study.
* Subject agrees to refrain from intensive physical exercise (disproportionate to the subjects' usual daily activity or exercise routine) for twenty-one days following each immunization and during the malaria challenge period.

Exclusion Criteria

* Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, hematological, infectious, immune-deficient, psychiatric or other disorders, which could compromise the health of the volunteer 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 weight \<50 kg or Body Mass Index (BMI) \<18.0 or \>30.0 kg/m2 at screening.

b. A heightened risk of cardiovascular disease, defined as: An estimated ten-year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); i. An estimated ten-year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); 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. 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. 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 function in the period of one year prior to study onset, positive urine toxicology test for cocaine, amphetamines or cannabis at screening.
* For female subjects: breastfeeding, or positive urine pregnancy test at screening or prior to immunization or prior to CHMI.
* Any history of malaria, positive serology for Pf, or previous participation in any malaria (vaccine) study or CHMI.
* Known hypersensitivity to or contra-indications (including co-medication) for use of atovaquone/proguanil or artemether/lumefantrine, or history of severe (allergic) reactions to MB.
* Receipt of any vaccinations in the three months prior to the start of the study or plans to receive any other vaccinations during the study period or up to eight weeks thereafter. Exceptions are made for influenza vaccination and for vaccination against the coronavirus SARS-COV2 or any other vaccination which cannot be reasonably withheld or postponed.
* Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
* Being an employee or student of the department of Parasitology, Medical Microbiology or Infectious Diseases of the RadboudUMC or the LUMC.
* Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol or would compromise the integrity of the data.

Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes