MalariaPhase 1NCT03163121

Safety and Protective Efficacy of Genetically Attenuated PfSPZ-GA1 Vaccine in Healthy Dutch Volunteers

A Phase 1 study testing PfSPZ-GA1 Vaccine, PfSPZ Vaccine and Normal Saline in people with Malaria, run by Sanaria Inc. at 2 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 35 yearsHealthy volunteers can take part
Conditions the study is for: Malaria
What is being tested?: PfSPZ-GA1 Vaccine, PfSPZ Vaccine and Normal Saline
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 67 participants
Where: 2 sitesNetherlands
Study dates: 12 May 2017to 25 Oct 2018
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 35 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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).

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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.

Who cannot join

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

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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.
Being an employee or student of the department of Medical Microbiology or Infectious Diseases of the Radboudumc or the LUMC.
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 would compromise the integrity of the data.

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

Leiden University Medical Center, Albinusdreef 2
Leiden, 2333 ZA
Radboud University Medical Center, Geert Grooteplein 28
Nijmegen, 6525 GA

Other trials in Netherlands

About this study

Official title: Safety and Protective Efficacy of Genetically Attenuated Pf∆b9∆Slarp (PfSPZ-GA1) Malaria Parasites in Healthy Dutch Volunteers

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.

Read the detailed description

Stage A, a Phase 1 dose-escalation study, will take place at Leiden University Medical Centre (LUMC). Stage B, a randomized, double-blind, placebo-controlled trial, will be conducted at LUMC and Radboudumc University Medical Centers (RUMC).

In Stage A, 19 healthy, adult volunteers will be allocated into three groups to receive increasing doses of PfSPZ-GA1 Vaccine by DVI. Group 1 (n=3) will receive one dose of 1.35 x 10^5 PfSPZ of PfSPZ-GA1 Vaccine. If this dose is safe for 28 days after inoculation, then Group 2 (n=3) will receive one dose of 4.5 x 10^5 PfSPZ of PfSPZ-GA1 Vaccine. If this dose is safe for 28 days after inoculation, Group 3 (n=13) will receive one dose of 9.0 x 10^5 PfSPZ of PfSPZ-GA1 Vaccine. 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.

If inoculation is deemed safe after 28 days for Group 3 and criteria for proceeding to Stage B are met, the trial will continue to Stage B. In Stage B, 48 healthy, adult volunteers will be randomized into four groups at 2 centers, LUMC and RUMC (24 volunteers at each site). Each group will receive 3 repeat doses, 8 weeks apart, of PfSPZ-GA1 Vaccine (low and high doses), PfSPZ Vaccine (radiation attenuated sporozoites), or normal saline (NS) placebo (as control) via DVI. Group 4 (n=13) will receive 9.0 x 10^5 PfSPZ of PfSPZ-GA1 Vaccine/dose. Group 5 (n=13) will receive 4.5 x 10^5 PfSPZ of PfSPZ-GA1 Vaccine/dose. Groups 6 (n=13) and 7 (n=9) will receive 4.5 x 10^5 PfSPZ Vaccine and NS placebo per dose, respectively. Three weeks after the last inoculation, all immunized volunteers and placebo controls (Group 7) will undergo a CHMI with five NF54-infected mosquitoes (wild-type) to determine degree of protection. After the 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 alternatively artemether/lumefantrine dosed according to Dutch clinical practice, 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.

Conditions: Malaria
Being tested: PfSPZ-GA1 Vaccine, PfSPZ Vaccine, Normal Saline, Mosquito-bite CHMI
Keywords: Plasmodium falciparum, PfSPZ Vaccine, PfSPZ-GA1 Vaccine, Controlled human malaria infection (CHMI), Genetically attenuated sporozoites, Plasmodium falciparum sporozoites (PfSPZ)
Medical subject headings: Malaria, Malaria, Falciparum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PfSPZ-GA1 VaccineBiological
Aseptic, purified, cryopreserved, genetically attenuated P. falciparum sporozoites (Pf∆b9∆slarp), strain NF54
PfSPZ VaccineBiological
Aseptic, purified, cryopreserved, radiation attenuated P. falciparum sporozoites (PfSPZ Vaccine), strain NF54
Normal SalineOther
0.9% sodium chloride
Mosquito-bite CHMIBiological
Bites of 5 infected mosquitoes of NF54 strain

Study groups in NCT03163121
Study group	Role	What they receive
Group 1 - PfSPZ-GA1 Vaccine	Experimental	Group 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. Receives: Biological: PfSPZ-GA1 Vaccine
Group 2 - PfSPZ-GA1 Vaccine	Experimental	Group 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. Receives: Biological: PfSPZ-GA1 Vaccine
Group 3 - PfSPZ-GA1 Vaccine	Experimental	Group 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. Receives: Biological: PfSPZ-GA1 Vaccine
Group 4 - PfSPZ-GA1 Vaccine	Experimental	Group 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. Receives: Biological: PfSPZ-GA1 Vaccine; Biological: Mosquito-bite CHMI
Group 5 - PfSPZ-GA1 Vaccine	Experimental	Group 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. Receives: Biological: PfSPZ-GA1 Vaccine; Biological: Mosquito-bite CHMI
Group 6 - PfSPZ Vaccine	Experimental	Group 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. Receives: Biological: PfSPZ Vaccine; Biological: Mosquito-bite CHMI
Group 7 - Normal Saline Placebo control	Placebo comparator	Group 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. Receives: Other: Normal Saline; Biological: Mosquito-bite CHMI

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: From time of inoculation to end of study, assessed up to 17 months

Secondary outcomes (1)

Presence of parasitemia after CHMI in Stage B
Presence of parasitemia after CHMI with the wild-type NF54 strain, as detected by qPCR
Measured: From time of inoculation to till 28 days later

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 May 201725 Oct 2018

First posted22 May 2017
Study start12 May 2017
Primary completion25 Oct 2018
Study completion25 Oct 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for MalariaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 67 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03163121
Sponsor's protocol ID: GA1
Other IDs: NL56657.000.16, 2016-000893-39, 2016
Status last verified: Mar 2019
First submitted: 19 May 2017
Last updated: 5 Mar 2019
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 25407681

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety and Protective Efficacy of Genetically Attenuated Pf∆b9∆Slarp (PfSPZ-GA1) Malaria Parasites in Healthy Dutch Volunteers
ClinicalTrials.gov ID: NCT03163121
Acronym / sponsor ID: GA1
Conditions: Malaria
Keywords: Plasmodium falciparum, PfSPZ Vaccine, PfSPZ-GA1 Vaccine, Controlled human malaria infection (CHMI), Genetically attenuated sporozoites, Plasmodium falciparum sporozoites (PfSPZ)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 67 participants (actual)
Lead sponsor: Sanaria Inc.Industry (pharma, biotech, devices)
Collaborators: Radboud University Medical Center, Leiden University Medical Center
Study start: 12 May 2017 (actual)
Primary completion: 25 Oct 2018 (actual)
Study completion: 25 Oct 2018 (actual)
First posted: 22 May 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 7

Arm	Type	Receives
Group 1 - PfSPZ-GA1 Vaccine	Experimental	Biological: PfSPZ-GA1 VaccineGroup 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	Experimental	Biological: PfSPZ-GA1 VaccineGroup 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	Experimental	Biological: PfSPZ-GA1 VaccineGroup 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	Experimental	Biological: PfSPZ-GA1 Vaccine, Biological: Mosquito-bite CHMIGroup 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	Experimental	Biological: PfSPZ-GA1 Vaccine, Biological: Mosquito-bite CHMIGroup 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	Experimental	Biological: PfSPZ Vaccine, Biological: Mosquito-bite CHMIGroup 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 comparator	Other: Normal Saline, Biological: Mosquito-bite CHMIGroup 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.

Who may qualify

Ages: 18 to 35 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

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.

Key exclusion criteria (17 listed)

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:
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PfSPZ-GA1 VaccineAseptic, purified, cryopreserved, genetically attenuated P. falciparum sporozoites (Pf∆b9∆slarp), strain NF54	Biological	Group 1 - PfSPZ-GA1 Vaccine, Group 2 - PfSPZ-GA1 Vaccine, Group 3 - PfSPZ-GA1 Vaccine, Group 4 - PfSPZ-GA1 Vaccine, Group 5 - PfSPZ-GA1 Vaccine
PfSPZ VaccineAseptic, purified, cryopreserved, radiation attenuated P. falciparum sporozoites (PfSPZ Vaccine), strain NF54	Biological	Group 6 - PfSPZ Vaccine
Normal Saline0.9% sodium chloride	Other	Group 7 - Normal Saline Placebo control
Mosquito-bite CHMIBites of 5 infected mosquitoes of NF54 strain	Biological	Group 4 - PfSPZ-GA1 Vaccine, Group 5 - PfSPZ-GA1 Vaccine, Group 6 - PfSPZ Vaccine, Group 7 - Normal Saline Placebo control

Primary outcome

Presence of blood stage parasites after inoculation with PfSPZ-GA1 Vaccine in Stage A
Time frame: From time of inoculation to till 28 days later
Presence of blood stage parasites after inoculation with PfSPZ-GA1 vaccine, as assessed by qPCR
Frequency and magnitude of adverse events in study groups in Stage A and B
Time frame: From time of inoculation to end of study, assessed up to 17 months
Frequency and magnitude of adverse events in study groups

1 secondary outcome

Presence of parasitemia after CHMI in Stage B
Time frame: From time of inoculation to till 28 days later

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
Background: PubMed 25407681van 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert W. Sauerwein, MD principal investigator

Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands

Leo G Visser, MD principal investigator

Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PfSPZ-GA1 Vaccine, PfSPZ Vaccine and Normal Saline in people with Malaria, run by Sanaria Inc. at 2 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Presence of blood stage parasites after inoculation with PfSPZ-GA1 Vaccine in Stage A (time frame: From time of inoculation to till 28 days later). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03163121, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2019.