Safety, Tolerability and Plasmodium falciparum transmission-reducing activity of R0.6C vaccine adjuvanted with Alhydrogel alone or combined with Matrix-M in healthy malaria-naïve adults in the Netherlands
- Conditions
- malariaPlasmodium falciparum10037072
- Registration Number
- NL-OMON51178
- Lead Sponsor
- Radboud Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 32
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 <= 55
years and in good health.
3. Subject is able to understand planned study procedures and demonstrate
comprehension of the protocol procedures and knowledge of study by passing a
quiz (assessment of understanding).
4. In the opinion of the investigator, the subject can and will comply with the
requirements of the protocol.
5. Subjects are available to attend all study visits and are reachable by phone
throughout the entire study period from day -1 until day 224 (end of study).
6. The subject will remain within reasonable travelling distance from the study
center from day -1 until day 7 after each R0.6C administration and agrees not
to travel to a malaria-endemic area during the study period
7. Subject agrees to their general practitioner (GP) being informed about
participation in the study and agrees to sign a form to request the release by
their GP, and medical specialist when necessary, of any relevant medical
information concerning possible contra-indications for participation in the
study to the investigator(s).
8. The subject agrees to refrain from blood donation to Sanquin or for other
purposes throughout the study period according to current Sanquin guidelines.
9. Female subjects of non-childbearing potential may be enrolled in the study.
All subjects of childbearing potential must agree to use continuous adequate
contraception until 2 months after completion of the study. Female subjects
must agree not to breastfeed from 30 days prior to R0.6C administration until 2
months after completion of the study. Female subjects must have a negative
pregnancy test at the inclusion visit.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary safety endpoints:<br /><br>1) The number of serious adverse events and solicited and unsolicited grade 3<br /><br>adverse events possibly, probably or definitely related to the vaccine in the<br /><br>period from first R0.6C administration up to 84 days after the last<br /><br>immunization.<br /><br>Primary efficacy endpoints:<br /><br>1) The functional TRA in the standard membrane feeding assay of volunteer sera<br /><br>collected two weeks after the fourth R0.6C immunization (I4+14), compared to<br /><br>baseline (I1-1) within each of the four dose-adjuvant groups. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary safety endpoints:<br /><br>1) The number of solicited and unsolicited grade 1 and 2 adverse events<br /><br>possibly, probably or definitely related to the vaccine in the period from<br /><br>first R0.6C administration up to 84 days after the last immunization.<br /><br>Secondary efficacy endpoints:<br /><br>1) The TRA at other timepoints (I1+14, I2+14, I3+14, I3+111 [I4-1], and I4+84)<br /><br>compared to baseline (I1-1) in each of the four dose-adjuvant groups.<br /><br>2) The anti-6C antibody quantity in volunteer sera collected two weeks after<br /><br>fourth R0.6C immunization (I4+14) and at other time points (I1+14, I2+14,<br /><br>I3+14, I3+111 [I4-1], and I4+84) compared to baseline (I1-1) in each of the<br /><br>four dose-adjuvant combinations, as determined by ELISA.</p><br>