Safety and Protective Efficacy of Genetically Attenuated PfSPZ-GA1 Vaccine in Healthy Dutch Volunteers
3 other identifiers
interventional
67
1 country
2
Brief Summary
This is a first-in-human, randomized clinical trial of PfSPZ-GA1 Vaccine (genetically attenuated PfSPZ) in healthy malaria-naïve adult volunteers. This Phase 1 trial is divided into two stages, Stage A and B. Stage A is an open label, single center, dose escalation study in 19 volunteers. Stage B is a multi-center, double blind, randomized, placebo-controlled trial in 48 volunteers. The primary objective of this study is to determine the safety and tolerability of direct venous inoculation (DVI) of PfSPZ-GA1 Vaccine in healthy adults.
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 2017
2 active sites
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
Study Start
First participant enrolled
May 12, 2017
CompletedFirst Submitted
Initial submission to the registry
May 19, 2017
CompletedFirst Posted
Study publicly available on registry
May 22, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 25, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
October 25, 2018
CompletedMarch 5, 2019
March 1, 2019
1.5 years
May 19, 2017
March 4, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Presence of blood stage parasites after inoculation with PfSPZ-GA1 Vaccine in Stage A
Presence of blood stage parasites after inoculation with PfSPZ-GA1 vaccine, as assessed by qPCR
From time of inoculation to till 28 days later
Frequency and magnitude of adverse events in study groups in Stage A and B
Frequency and magnitude of adverse events in study groups
From time of inoculation to end of study, assessed up to 17 months
Secondary Outcomes (1)
Presence of parasitemia after CHMI in Stage B
From time of inoculation to till 28 days later
Study Arms (7)
Group 1 - PfSPZ-GA1 Vaccine
EXPERIMENTALGroup 1 will comprise of 3 volunteers who will receive one immunization of 1.35 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine via DVI. Volunteers will be followed closely for monitoring of adverse events and possible breakthrough blood infections by testing for the presence of parasitemia by qPCR. All volunteers will be treated with a curative regimen of atovaquone/proguanil (A/P) should break-through parasites be detected in the peripheral blood, or at the end of the follow-up period (28 days) if they are not qPCR positive. Six months after the inoculation, a final visit will take place to assess adverse events.
Group 2 - PfSPZ-GA1 Vaccine
EXPERIMENTALGroup 2 will comprise of 3 volunteers who will receive one immunization of 4.5 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine via DVI. Volunteers will be followed closely for monitoring of adverse events and possible breakthrough blood infections by testing for the presence of parasitemia by qPCR. All volunteers will be treated with a curative regimen of atovaquone/proguanil (A/P) should break-through parasites be detected in the peripheral blood, or at the end of the follow-up period (28 days) if they are not qPCR positive. Six months after the inoculation, a final visit will take place to assess adverse events.
Group 3 - PfSPZ-GA1 Vaccine
EXPERIMENTALGroup 3 will comprise of 13 volunteers who will receive one immunization of 9.0 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine via DVI. Volunteers will be followed closely for monitoring of adverse events and possible breakthrough blood infections by testing for the presence of parasitemia by qPCR. All volunteers will be treated with a curative regimen of atovaquone/proguanil (A/P) should break-through parasites be detected in the peripheral blood, or at the end of the follow-up period (28 days) if they are not qPCR positive. Six months after the inoculation, a final visit will take place to assess adverse events.
Group 4 - PfSPZ-GA1 Vaccine
EXPERIMENTALGroup 4 will comprise of 13 volunteers who will receive 3 immunizations of 9.0 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine 8 weeks apart via DVI. 3 weeks after the last injection, volunteers will undergo mosquito-bite CHMI with five NF54-infected mosquitoes. After CHMI, volunteers will be followed closely for monitoring of adverse events and blood stage infections, and will be seen once daily from day 6 until day 21 after infection and on day 28. All volunteers will be treated with a curative regimen of antimalarials, which may be A/P or artemether/lumefantrine, at the time of detection of blood stage parasitemia by qPCR or 28 days after CHMI. Adverse events will be assessed up to 6 months after the CHMI.
Group 5 - PfSPZ-GA1 Vaccine
EXPERIMENTALGroup 5 will comprise of 13 volunteers who will receive 3 immunizations of 4.5 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine 8 weeks apart via DVI. 3 weeks after the last injection, volunteers will undergo mosquito-bite CHMI with five NF54-infected mosquitoes. After CHMI, volunteers will be followed closely for monitoring of adverse events and blood stage infections, and will be seen once daily from day 6 until day 21 after infection and on day 28. All volunteers will be treated with a curative regimen of antimalarials, which may be A/P or artemether/lumefantrine, at the time of detection of blood stage parasitemia by qPCR or 28 days after CHMI. Adverse events will be assessed up to 6 months after the CHMI.
Group 6 - PfSPZ Vaccine
EXPERIMENTALGroup 6 will comprise of 13 volunteers who will receive 3 immunizations of 4.5 x 10\^5 PfSPZ of PfSPZ Vaccine 8 weeks apart via DVI. 3 weeks after the last injection, volunteers will undergo mosquito-bite CHMI with five NF54-infected mosquitoes. After CHMI, volunteers will be followed closely for monitoring of adverse events and blood stage infections, and will be seen once daily from day 6 until day 21 after infection and on day 28. All volunteers will be treated with a curative regimen of antimalarials, which may be A/P or artemether/lumefantrine, at the time of detection of blood stage parasitemia by qPCR or 28 days after CHMI. Adverse events will be assessed up to 6 months after the CHMI.
Group 7 - Normal Saline Placebo control
PLACEBO COMPARATORGroup 7 will comprise of 9 volunteers who will receive 3 injections of normal saline placebo 8 weeks apart via DVI. 3 weeks after the last injection, volunteers will undergo mosquito-bite CHMI with five NF54-infected mosquitoes. After CHMI, volunteers will be followed closely for monitoring of adverse events and blood stage infections, and will be seen once daily from day 6 until day 21 after infection and on day 28. All volunteers will be treated with a curative regimen of antimalarials, which may be A/P or artemether/lumefantrine, at the time of detection of blood stage parasitemia by qPCR or 28 days after CHMI. Adverse events will be assessed up to 6 months after the CHMI.
Interventions
Aseptic, purified, cryopreserved, genetically attenuated P. falciparum sporozoites (Pf∆b9∆slarp), strain NF54
Aseptic, purified, cryopreserved, radiation attenuated P. falciparum sporozoites (PfSPZ Vaccine), strain NF54
Bites of 5 infected mosquitoes of NF54 strain
Eligibility Criteria
You may qualify if:
- Subject is aged ≥ 18 and ≤ 35 years and in good health.
- Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
- Subject is able to communicate well with the investigator, is available to attend all study visits.
- Furthermore, the subject will remain within the Netherlands from day -1 till day +28 after each parasite exposure. After CHMI, subjects have to be reachable by phone (24/7) from day -1 until day 35.
- Subject agrees to inform his/her general practitioner (GP) about participation in the study and to sign a request to release by the GP, and medical specialist when necessary, any relevant medical information concerning possible contra-indications for participation in the study.
- 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 (3 years minimum, depending on serology).
- Non-pregnant, non-lactating females of reproductive potential (i.e., have a uterus and are neither surgically sterilized nor post-menopausal) should agree to use adequate contraception and not to breastfeed for the duration of study.
- 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.
- Subject has signed informed consent.
You may not qualify if:
- 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:
- Body weight \< 50 kg or Body Mass Index (BMI) \< 18.0 or \> 30.0 kg/m\^2 at screening
- 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
- Functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD deficiency
- History of epilepsy in the period of five years prior to study onset, even if no longer on medication
- Positive HIV, HBV or HCV screening tests
- Chronic use of i) immunosuppressive drugs, ii) antibiotics, or iii) other immune modifying drugs within three months prior to study onset (excluding inhaled and topical corticosteroids and incidental use of oral anti-histamines) or expected use of such during the study period
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past five years
- Any history of treatment for severe psychiatric disease by a psychiatrist in the past year
- 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 infection or positive urine toxicology test for cannabis prior to infection.
- For female subjects: breastfeeding, or positive urine pregnancy test at screening or prior to immunization or prior to CHMI.
- Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study or CHMI.
- 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.
- Receipt of any vaccinations in the 3 months prior to the start of the study or plans to receive any other vaccinations during the study period or up to 8 weeks thereafter.
- Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sanaria Inc.lead
- Radboud University Medical Centercollaborator
- Leiden University Medical Centercollaborator
Study Sites (2)
Leiden University Medical Center, Albinusdreef 2
Leiden, 2333 ZA, Netherlands
Radboud University Medical Center, Geert Grooteplein 28
Nijmegen, 6525 GA, Netherlands
Related Publications (1)
van Schaijk BC, Ploemen IH, Annoura T, Vos MW, Foquet L, van Gemert GJ, Chevalley-Maurel S, van de Vegte-Bolmer M, Sajid M, Franetich JF, Lorthiois A, Leroux-Roels G, Meuleman P, Hermsen CC, Mazier D, Hoffman SL, Janse CJ, Khan SM, Sauerwein RW. A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites. Elife. 2014 Nov 19;3:e03582. doi: 10.7554/eLife.03582.
PMID: 25407681BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert W. Sauerwein, MD
Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands
- PRINCIPAL INVESTIGATOR
Leo G Visser, MD
Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Stage A is an open label study. Stage B of the clinical study will be double-blinded.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 19, 2017
First Posted
May 22, 2017
Study Start
May 12, 2017
Primary Completion
October 25, 2018
Study Completion
October 25, 2018
Last Updated
March 5, 2019
Record last verified: 2019-03
Data Sharing
- IPD Sharing
- Will not share