malaria Plasmodium falciparum
Conditions
Interventions
Each of the study arms will receive four intramuscular vaccinations on days 0,
28, 56 and 168 with R0.6C adsorbed to Alhydrogel alone (Groups 1-4A), or
combined with an additional adjuvant Matrix-M
subsequently
the additional subjects (groups 2A and 2B, n=5 per arm) will receive the low
dose of 30 µg R0.6C
if considered safe, a sentinel group (3A and 3B, n=3 per
arm) will receive the high dose of 100µg R0.6C
and finally, the remainder of
subjects will receive the high dose of 100µg R0.6C (groups 4A and 4B, n=5 per
arm).
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Subject must sign written informed consent to participate in the trial. 2. Subject is a male or non-pregnant and non-lactating female age >= 18 and
Exclusion criteria
Exclusion criteria: 1. Acute or chronic disease at time of R0.6C administration, clinically significant pulmonary, cardiovascular, hepatic, renal, neurological or immunological functional abnormality, as determined by medical history, physical examination or laboratory screening tests: a. Acute disease is defined as the presence of a moderate or severe illness with or without fever. For subjects with an illness on the day of R0.6C administration, the vaccination may be postponed up to 7 days. b. Fever is defined as an oral, axillary or tympanic temperature >= 38.0°C. c. Any abnormal and clinically significant baseline laboratory screening tests of ALT, AST, creatinine, hemoglobin, platelet count or total white blood cell count, as defined in the protocol according to the FDA Toxicity Grading Scale for Healthy Adult and Adolescent Subjects Enrolled in Preventative Vaccine Clinical Trials (appendix 1). 2. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years. 3. Chronic use of i) immunosuppressive drugs, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period. 4. 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 at inclusion. 5. Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV). 6. Use of any other investigational or non-registered product (drug or vaccine) during the study period. 7. Known hypersensitivity to macrolides. 8. Participation in any other clinical study involving an investigational product in the 30 days prior to the start of the study or during the study period. 9. Receipt of any other vaccination within 30 days prior to or up to 14 days after any R0.6C vaccination. Exceptions are made for vaccination against influenza and the novel coronavirus SARS-CoV2. 10. Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study or CHMI. 11. Body weight > 115 kg 12. Being an employee or student of the department of Medical Microbiology of the Radboudumc at the time of screening, or a person otherwise related to the investigator. 13. 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 affects the interpretability of the trial results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary safety endpoints: 1) The number of serious adverse events and solicited and unsolicited grade 3 adverse events possibly, probably or definitely related to the vaccine in the period from first R0.6C administration up to 84 days after the last immunization. Primary efficacy endpoints: 1) The functional TRA in the standard membrane feeding assay of volunteer sera collected two weeks after the fourth R0.6C immunization (I4+14), compared to baseline (I1-1) within each of the four dose-adjuvant groups. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary safety endpoints: 1) The number of solicited and unsolicited grade 1 and 2 adverse events possibly, probably or definitely related to the vaccine in the period from first R0.6C administration up to 84 days after the last immunization. Secondary efficacy endpoints: 1) The TRA at other timepoints (I1+14, I2+14, I3+14, I3+111 [I4-1], and I4+84) compared to baseline (I1-1) in each of the four dose-adjuvant groups. 2) The anti-6C antibody quantity in volunteer sera collected two weeks after fourth R0.6C immunization (I4+14) and at other time points (I1+14, I2+14, I3+14, I3+111 [I4-1], and I4+84) compared to baseline (I1-1) in each of the four dose-adjuvant combinations, as determined by ELISA. | — |
Countries
Netherlands
Outcome results
None listed