Sanaria PfSPZ Challenge With Pyrimethamine or Chloroquine Chemoprophylaxis Vaccination (PfSPZ-CVac Approach): A Randomized Double Blind Placebo Controlled Phase I/II Trial to Determine Safety and Protective Efficacy Against Natural Plasmodium Falcipa...
2 other identifiers
interventional
252
1 country
1
Brief Summary
Background: Malaria remains a major global health problem. Malaria is spread by the bite of mosquitos. Africa is the region of the world where most people get malaria. Sanaria PfSPZ Challenge is a malaria vaccine. Researchers want to see if the vaccine combined with partner drugs can help protect against malaria. Objective: To test if injections with 3 monthly doses of Sanaria PfSPZ Challenge, combined with either pyrimethamine (PYR) or chloroquine as a partner drug, is safe, tolerable, and effective. Eligibility: Healthy people ages 18-50 years who live in Bancoumana, Mali, or nearby Design: Participants will be screened with the Malaria Comprehension Exam to check their understanding of the study. They will have a medical history. They will have a physical exam. They will have blood tests, urine tests, and heart tests. Participants will join either the pilot study or the main study. Participants will be assigned to groups. Depending on their group, they will get at least one injection of either a placebo or the vaccine. They may have up to 3 vaccines, 4 weeks apart. The injection will be into a vein with a needle. Participants will also take pyrimethamine or chloroquine by mouth. They will also take standard doses of antimalarial drugs by mouth. Participants will have blood tests throughout the study. Participants may develop a rash or injection site reaction. If this happens, photos of the site may be taken. Participants will be observed for infection for many days after the injections.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2019
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 15, 2019
CompletedFirst Posted
Study publicly available on registry
May 16, 2019
CompletedStudy Start
First participant enrolled
May 23, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 10, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 10, 2021
CompletedResults Posted
Study results publicly available
July 12, 2022
CompletedJuly 12, 2022
July 1, 2021
1.7 years
May 15, 2019
February 7, 2022
June 21, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Number of Participants With Positive Sensitive Blood Smear (sBS)
Count of participants with positive sensitive blood smear (sBS) occurring after PfSPZ-CVac immunization starting on day 7 post DVI. Only pilot phase arms (Arms 1a, 2a) were analyzed for this outcome measure. Arms 5a and 6a were not performed, as no patent parasitemia was observed in either Arms 1a or 2a, per the protocol.
7 -12 days post-inoculation
Number of Participants With Local and Systemic Grade 3 Adverse Events (AEs) and Serious Adverse Events (SAEs)
Count of participants with local and systemic grade 3 signs or symptoms lasting more than 48 hours despite adequate management and serious adverse events (SAEs) occurring after PfSPZ-CVac DVI. Only arm 3a was analyzed for this outcome measure, per the protocol objectives.
From day of inoculation to 14 days post-inoculation
Number of Participants With Local and Systemic Adverse Events (AEs) and Serious Adverse Events (SAEs)
Count of participants with local and systemic adverse events (AEs) and serious adverse events (SAEs) occurring after PfSPZ-CVac immunization. This outcome measure applies to main phase arms 1b, 2b, 4a, and 4b. Arms 5b and 6b were not performed as patent parasitemia with the higher dose of PfSPZ was not observed in the pilot phase (Arms 1a, 2a).
For the main phase: from the day of inoculation to approximately 6 months post-3rd inoculation. For the booster phase: from the time of inoculation to approximately 6 months post-booster inoculation
Study Arms (13)
1a
EXPERIMENTALReceiving 400,000 PfSPZ with 75 mg pyrimethamine day 0 post PfSPZ
1b
EXPERIMENTALReceiving 400,000 PfSPZ with 75 mg pyrimethamine day 0 post PfSPZ
2a
EXPERIMENTALReceiving 400,000 PfSPZ with 75 mg pyrimethamine days 2\&3 post PfSPZ
2b
EXPERIMENTALReceiving 400,000 PfSPZ with 75 mg pyrimethamine days 2\&3 post PfSPZ
3a
EXPERIMENTALReceiving 400,000 PfSPZ with chloroquine 2 days prior + 5 days post PfSPZibuprofen (if necessary)
3b
EXPERIMENTALReceiving 400,000 PfSPZ with weekly chloroquineibuprofen (if necessary)
4a
PLACEBO COMPARATORReceiving normal saline with 75 mg pyrimethamine day 0 post injection
4b
PLACEBO COMPARATORReceiving normal saline with 75 mg pyrimethamine days 2\&3 post injection
4c
PLACEBO COMPARATORReceiving normal saline with weekly chloroquineibuprofen (if necessary)
5a
EXPERIMENTALReceiving 300,000 PfSPZ with 75 mg pyrimethamine day 0 post PfSPZ (if necessary)
5b
EXPERIMENTALReceiving 300,000 PfSPZ with 75 mg pyrimethamine day 0 post PfSPZ
6a
EXPERIMENTALReceiving 300,000 PfSPZ with 75 mg pyrimethamine days 2\&3 post PfSPZ (if necessary)
6b
EXPERIMENTALReceiving 300,000 PfSPZ with 75 mg pyrimethamine days 2\&3 post PfSPZ (if necessary)
Interventions
Chloroquine phosphate is approved for suppressive treatment (prophylaxis) and for acute attacks of malaria due to P. vivax, P. malariae, P. ovale, and susceptible strains of Pf. Chloroquine is a blood-stage schizonticide, highly active against replicating forms of blood-stage drug- sensitive parasites. As such, it is routinely employed as first-line prophylaxis against development of patent parasitemia and clinical malaria in non-immune travelers to areas with chloroquine sensitive Pf. In the pilot, chloroquine administration will begin with a loading dose 2 days prior to PfSPZ Challenge and finishing with a maintenance dose 5 days after PfSPZ Challenge. In the main phase, chloroquine will be first administered as a loading dose 2 days prior to PfSPZ Challenge and continuing weekly using a maintenance dose for a total of 10 doses, finishing with a last dose 5 days after the third injection with PfSPZ Challenge.
PfSPZ Challenge (NF54) acts as the immunogen in the PfSPZ-CVac approach to vaccinating against malaria. Participants will receive either one (in the pilot phase) or 3 (in the main phase) 400,000 or 300,000 aseptic, purified, cryopreserved, fully infectious PfSPZ injections by DVI (with concurrent administration of antimalarial drugs). Following immunization, participants in the main phase will be followed through the transmission season in order to assess vaccine efficacy.
Pyrimethamine has been FDA approved for acute treatment and chemoprophylaxis of malaria due to susceptible strains of plasmodia. Pyrimethamine has been shown to possess both liver and blood stage activity. In this study, we plan to use a higher dose of pyrimethamine, 75 mg orally for either one or two days each month. The pilot arms will receive either a total of 1 daily dose or 2 daily doses. The main arms will receive a total of 3 daily doses or a total of 6 doses.
Antimalarial (Coartem ) will be administered to all participants twice during the study, approximately 2 weeks prior to the first vaccination in order to clear pre-existing parasitemia that may interfere with immunity development. The second dose will be given approximately 2 weeks prior to the 3rd vaccination in order to clear any parasitemia infection that may have happened naturally during the vaccination period and prior to the follow up period.
Ibuprofen likewise is not a part of the investigational product/regimen, but will be provided to participants in the chloroquine arm (Arm 4) if required to mitigate typical symptoms of malaria infection such as headache, myalgia, fever and chills.
Eligibility Criteria
You may qualify if:
- Age greater than or equal to 18 and less than or equal to 50 years (for booster phase, age greater than or equal to 18 and less than or equal to 52 years)
- Resident of Bancoumana or nearby areas
- In good general health and without clinically significant medical history
- Malaria comprehension exam completed, passed (a score of greater than or equal to 80% or per investigator s discretion) and reviewed prior to enrollment
- Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
- Willing to have blood samples stored for future research
- Available for the duration of the study
- Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to first PfSPZ Challenge injection to 28 days following last PfSPZ Challenge exposure (or equivalent study day for Arm 5 controls). For the booster phase, this applies from 21 days prior to the booster vaccination to 28 days post booster vaccination.
- Reliable methods of birth control include one of the following: confirmed pharmacologic contraceptives (parenteral) delivery; intrauterine or implantable device. OR
- Reliable methods of birth control include concurrent use of a pharmacologic and a barrier method, i.e., two of the following: confirmed pharmacologic contraceptives (oral, transdermal) delivery or vaginal ring AND condoms with spermicide or diaphragm with spermicide. OR
- Non-childbearing women will also be required to report date of last menstrual period, history of surgical sterility (i.e. tubal ligation, hysterectomy) or premature ovarian insufficiency (POI), and will have urine or serum pregnancy test performed per protocol.
- For booster phase only: previously or currently enrolled in protocol #19-I-N099 and completed all three primary vaccinations.
You may not qualify if:
- Pregnancy, as determined by a positive urine or serum human choriogonadotropin (beta-hCG) test (if female)
- NOTE: Pregnancy is also a criterion for discontinuation of any further dosing or non-safety related interventions for that subject.
- Currently breast-feeding (if female)
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol
- Hemoglobin, WBC, absolute neutrophils, and platelets outside the local laboratorydefined limits of normal (subjects may be included at the investigator s discretion for 'not clinically significant' values)
- Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratoryMali PfSPZ-CVac (pyrimethamine) defined upper limit of normal (subjects may be included at the investigator s discretion for not clinically significant values)
- Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B (HBV) (For the booster phase: re-testing NOT required for enrollment unless clinically indicated)
- Clinically significant abnormal electrocardiogram (ECG) (For the booster phase: re-testing NOT required for enrollment unless clinically indicated)
- Moderate or high risk for coronary heart disease (CHD) based on NHANES I cardiovascular risk assessment
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis
- History of receiving any other investigational product within the past 30 days
- Participation or planned participation in a clinical trial with an investigational product prior to completion of the last required protocol follow-up visit
- Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
- History of a severe allergic reaction or anaphylaxis
- Severe asthma (defined as asthma that is unstable or required emergent care,urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years)
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Malaria Vaccine Center STTB/MRTC
Bamako, Mali
Related Publications (3)
Bijker EM, Borrmann S, Kappe SH, Mordmuller B, Sack BK, Khan SM. Novel approaches to whole sporozoite vaccination against malaria. Vaccine. 2015 Dec 22;33(52):7462-8. doi: 10.1016/j.vaccine.2015.09.095. Epub 2015 Oct 23.
PMID: 26469716BACKGROUNDMordmuller B, Surat G, Lagler H, Chakravarty S, Ishizuka AS, Lalremruata A, Gmeiner M, Campo JJ, Esen M, Ruben AJ, Held J, Calle CL, Mengue JB, Gebru T, Ibanez J, Sulyok M, James ER, Billingsley PF, Natasha KC, Manoj A, Murshedkar T, Gunasekera A, Eappen AG, Li T, Stafford RE, Li M, Felgner PL, Seder RA, Richie TL, Sim BK, Hoffman SL, Kremsner PG. Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. Nature. 2017 Feb 23;542(7642):445-449. doi: 10.1038/nature21060. Epub 2017 Feb 15.
PMID: 28199305BACKGROUNDRoestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.
PMID: 19641203BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Dave Cook
- Organization
- Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Study Officials
- PRINCIPAL INVESTIGATOR
Patrick E Duffy, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- OTHER
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 15, 2019
First Posted
May 16, 2019
Study Start
May 23, 2019
Primary Completion
February 10, 2021
Study Completion
February 10, 2021
Last Updated
July 12, 2022
Results First Posted
July 12, 2022
Record last verified: 2021-07