Safety and preliminary protective efficacy of genetically attenuated Pf*mei2 (GA2) malaria parasites in healthy Dutch volunteers

Completed

• Conditions: Malaria; parasitaire ziekte; 10037072

• Registration Number: NL-OMON51062
• Lead Sponsor: eids Universitair Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2023-12-11
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 51

Inclusion Criteria

1. Subject is aged >= 18 and <= 35 years and in good health.
2. Subject has adequate understanding of the procedures of the study and agrees
to abide strictly thereby.
3. Subject is able to communicate well with the investigator, is available to
attend all study visits.
4. Furthermore, the subject will remain within the Netherlands from day -1 till
day +28 after each parasite exposure. After exposure to parasites, subjects
have to be reachable by phone (24/7) from day -1 until day 35.
5. Subject agrees that his/her general practitioner (GP) will be informed about
participation in the study.
6. 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 (three years minimum, depending on serology).
7. Non-pregnant, non-lactating, fertile (i.e., have a uterus and are neither
surgically sterilized nor post-menopausal) female subjects agree to use
adequate contraception and to not breastfeed for the duration of study.
8. 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.
9. Subject signs informed consent.

Exclusion Criteria

1. 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, haematological, 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:
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 or amphetamines at screening or prior to exposure to parasites or
positive urine toxicology test for cannabis prior to exposure to parasites.
2. For female subjects: breastfeeding, or positive urine pregnancy test at
screening or prior to immunization or prior to CHMI.
3. Any history of malaria, positive serology for Pf, or previous participation
in any malaria (vaccine) study or CHMI.
4. Known hypersensitivity to or contra-indications (including co-medication)
for use of atovaquone/proguanil or artemether/lumefantrine, or history of
severe (allergic) reactions to mosquito bites.
5. 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,
if it becomes available during the study period, for vaccination against the
novel coronavirus SARS-COV2.
6. Participation in any other clinical study in the 30 days prior to the start
of the study or during the study period.
7. Being an employee or student of the department of Parasitology, Medical
Microbiology or Infectious Diseases of the LUMC or RUMC.
8. Any other condition or s

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoints:<br /><br>Phase 1:<br /><br>• Number of volunteers with blood-stage parasitaemia after exposure to the GA2<br /><br>parasite, as assessed by qPCR.<br /><br>• Number and magnitude of adverse events (AEs) and serious adverse events<br /><br>(SAEs).<br /><br><br /><br>Phase 2:<br /><br>• Number of volunteers protected against CHMI after immunisation with the GA2<br /><br>parasite.<br /><br>• Number and magnitude of AEs and SAEs. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints (Phase 1 and Phase 2):<br /><br>• Kinetics of cellular and humoral immune response of volunteers exposed to the<br /><br>GA2 and GA1 parasite. </p><br>