Safety, Tolerability and Immunogenicity of PfSPZ Vaccine in an Age De-escalation Trial in Equatorial Guinea.
Malaria
About this trial
This is an interventional prevention trial for Malaria focused on measuring Plasmodium falciparum, PfSPZ Vaccine, PfSPZ Challenge (NF54), CHMI, Chloroquine, Chemoprophylaxis, PfSPZ-CVac
Eligibility Criteria
Inclusion Criteria:
- Healthy males and females, based on clinical and laboratory findings
- From the age 6 months to 65 years
- Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or adolescents, children and infants with Z-score of the selected indicator ([weight-for-height], [(height and BMI) for age]) category within ±2SD as detailed in protocol
- Long-term (at least one year) or permanent residence in the Baney district or Malabo city
- Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study
- Willingness to be attended to by a study clinician and take all necessary medications prescribed during study period
- Agreement to provide contact information of a third party household member or close friend to study team
- Agreement not to participate in another clinical trial during the study period
- Agreement not to donate blood during the study period
- Able and willing to complete the study visit schedule over the study follow up period, including the hospitalizations required for protocol compliance
- .Willingness to undergo HIV, hepatitis B (HBV) and hepatitis C (HCV) tests
- Volunteer (subjects 18 years of age and older) or the parent / guardian signing the informed consent (for subjects <18 years of age) is able to demonstrate their understanding of the study by responding correctly to 10 out of 10 true/false statements (in a maximum of two attempts for those who failed to respond correctly to all true/false statements in the first attempt).
- Signed written informed consent, in accordance with local practice, provided by adult volunteers, parents or legal representatives and relevant assent for children participants as applicable.
- Free from malaria parasitemia by blood smear at enrollment and by PCR for group 1
- Has not been treated with any antimalarial medication for at least two weeks prior to the first immunization.
- Free from helminth infections (detected by microscopy) at enrollment.
- Female volunteers aged 9 years and above must be non-pregnant (as demonstrated by a negative urine pregnancy test), and provide consent/assent of their willingness to take protocol-defined measures not to become pregnant during the study and safety follow-up period.
Exclusion Criteria:
- Previous receipt of an investigational malaria vaccine in the last 5 years
- Participation in any other clinical study involving investigational medicinal products including investigational malaria drugs within 30 days prior to the onset of the study or during the study period
- History of arrhythmias or prolonged QT-interval or other cardiac disease, or clinically significant abnormalities in electrocardiogram (ECG) at screening
- Positive family history in a 1st or 2nd degree relative for cardiac disease at age <50 years old
- A history of psychiatric disease
- Suffering from any chronic illness including; diabetes mellitus, cancer or HIV/AIDS
- Any confirmed or suspected immunosuppressive or immune-deficient condition, including asplenia
- History of drug or alcohol abuse interfering with normal social function
- The use of chronic immunosuppressive drugs or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period
- Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis
- Positive HIV, hepatitis B virus or hepatitis C virus tests
- Volunteers who are have risk factors for tuberculosis and/or signs and symptoms of tuberculosis (TB), plus a positive tuberculin skin test (TST).
- Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, blood, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers
- Any medical, social condition, or occupational reason that, in the judgment of the investigator, is a contraindication to protocol participation or impairs the volunteer's ability to give informed consent, increases the risk to the volunteer because of participation in the study, affects the ability of the volunteer to participate in the study or impairs the quality, consistency or interpretation of the study data
- History of non-febrile seizures or atypical febrile seizures
Sites / Locations
- La Paz Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Experimental
Placebo Comparator
Group 1a (PfSPZ Vaccine)
Group 1a (normal saline)
Group 1b (PfSPZ CVac)
Group 1b (normal saline)
Group 2 (PfSPZ Vaccine)
Group 2 (normal saline)
Group 3 (PfSPZ Vaccine)
Group 3 (normal saline)
Group 4 (PfSPZ Vaccine)
Group 4 (normal saline)
Group 5 (PfSPZ Vaccine)
Group 5 (normal saline)
Group 6a (PfSPZ Vaccine)
Group 6b (PfSPZ Vaccine)
Group 6b (normal saline)
18-35 years; n= 20; 3 doses of 2.7x10^6 PfSPZ Vaccine given eight weeks apart. Volunteers will receive CHMI between 10 and 14 weeks post last vaccination (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI.
18-35 years; n=6; 3 doses of normal saline given 8 weeks apart. Volunteers will receive CHMI between 10 and 14 weeks post last dose of NS (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI.
18-35 years; n=20; 3 doses of 1.0x10^5 PfSPZ Challenge given every four weeks. Group 1b will start 8 weeks after Group 1a. Volunteers in Group 1b will receive their first immunization after the loading dose of chloroquine has been administered. Volunteers will receive CHMI between 10 and 14 weeks post last vaccination (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI.
18-35 years; n=6; 3 doses of normal saline given 4 weeks apart. Group 1b will start 8 weeks after Group 1a. Volunteers will receive CHMI between 10 and 14 weeks post last dose of NS (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI.
36-65 years; n=12; 3 doses of 2.7x10^6 PfSPZ Vaccine given 8 weeks apart. Group 2 will start 3 weeks after Group 1a.
36-65 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 2 will start 3 weeks after Group 1a.
11-17 years; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 3 will start 3 weeks after Group 1a.
11-17 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 3 will start 3 weeks after Group 1a.
6-10 years; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 4 will start 4 weeks after Group 1a.
6-10 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 4 will start 4 weeks after Group 1a.
1-5 years; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 5 will start 7 weeks after Group 1a.
1-5 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 5 will start 7 weeks after Group 1a.
6-11 months; n=3; 1 dose of 9.0x10^5 PfSPZ Vaccine. Group 6a will start 7 weeks after Group 1a.
6-11 months; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 6b will start 11 weeks after Group 1a.
6-11 months; n=4; 3 doses of normal saline given 8 weeks apart. Group 6b will start 11 weeks after Group 1a.