MalariaPhase 1NCT03510481
Safety, Immunogenicity, and Protective Efficacy of Two Regimens of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Natural Transmission Season in Healthy African Adults in Mali
A Phase 1 study testing PfSPZ Vaccine, Normal Saline and artemether 20mg/lumefantrine 120mg (AL) in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
Trial summary
Background: The disease malaria affects many people in Mali and other parts of Africa and the world. It is caused by germs spread by mosquito bites. Malaria may be mild. But it can also be serious or lead to death if it is not treated promptly. Researchers want to find a safe vaccine that prevents malaria. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- PfSPZ Vaccine, Normal Saline and artemether 20mg/lumefantrine 120mg (AL)
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 478 participants
- Where
- 1 siteMali
- Study dates
- 14 May 2018to 13 Feb 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age greater than or equal to 18 and less than or equal to 35 years
- Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
- In good general health and without clinically significant medical history
- 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 Study Day 1 to 28 days after last vaccination.
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- Reliable methods of birth control include:
- one of the following: confirmed pharmacologic contraceptives (parenteral) delivery; intrauterine or implantable device. OR
- two of the following: a documented oral or transdermal or vaginal ring contraceptives; PLUS condoms with spermicide or diaphragm with spermicide.
- Note, Coartem (artemether specifically) may reduce the effectiveness of systemic hormonal contraceptives, therefore additional barrier methods such as condoms must also be used during the 3 days of Coartem dosing.
- Women who are not able to get pregnant 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.
Who cannot join
- Pregnancy, as determined by a positive urine or serum human chorionic gonadotropin (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 (Hb), WBC, absolute neutrophils, and platelets outside the local laboratory- defined 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 laboratory-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)
Show all 25Show fewer
- Known or documented sickle cell disease by history (Note: known sickle cell trait is NOT exclusionary)
- Clinically significant abnormal electrocardiogram (ECG) such as abnormal QTc.
- 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 investigational product within the past 30 days
- Participation or planned participation in a clinical trial with an investigational product prior to completion of the follow-up visit 28 days following last vaccination OR planned participation in an investigational vaccine study until the last required protocol 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(Grade 3 or higher or per PI discretion) or anaphylaxis
- Severe asthma (defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past two years, or that has required the use of oral or parenteral corticosteroids at any time during the past two years)
- Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia
- Known immunodeficiency syndrome
- Known asplenia or functional asplenia
- Use of:
- Chronic (greater than or equal to 14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of vaccination
- Use of antimalarials or systemic antibiotics with known antimalarial activity within 5 drug half-lives prior to the first vaccine (such as artemether, artemether-lumefantrine, sulfadoxine-pyrimethamine, trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones or azithromycin)
- Receipt of a live vaccine within the past four weeks or a killed vaccine within the past two weeks prior to Vaccination #1 and every subsequent vaccination day
- Receipt of immunoglobulins and/or blood products within the past six months
- Previous receipt of an investigational malaria vaccine in the last five years
- Known allergies or other contraindications against Coartem
- Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a participant participating in the trial, interfere with the evaluation of the study objectives, or would render the subject unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety, Immunogenicity, and Protective Efficacy of Two Regimens of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Natural Transmission Season in Healthy African Adults in Mali
Background:
The disease malaria affects many people in Mali and other parts of Africa and the world. It is caused by germs spread by mosquito bites. Malaria may be mild. But it can also be serious or lead to death if it is not treated promptly. Researchers want to find a safe vaccine that prevents malaria.
Read more
Objective:
To study how safe and tolerable the malaria vaccine called PfSPZ Vaccine is for healthy adults.
Eligibility:
Healthy adults:
- ages 18-35 in Ouelessebougou, Mali
- not infected with HIV, hepatitis B, or hepatitis C
- for females, not pregnant or breastfeeding and must use reliable birth control during the study
Design:
Participants will be screened with questions about malaria and will undergo blood, urine, and heart tests.
Participants will be randomly assigned to 1 of 4 groups. They will get injections of either the PfSPZ Vaccine or a salt-water placebo. They will not know which one they get.
Vaccinations will occur leading into the malaria transmission each year with 3 injections leading into Year 1 (malaria transmission season in 2018) and 1 injection prior to Year 2 (malaria transmission season 2019).
One vaccine group and one placebo group will get an injection 3 times over 4 weeks with an additional vaccination ~10 months later.
The other two groups (vaccine group and placebo) will get an injection 3 times over 16 weeks with an additional vaccination ~10 months later.
All participants will be treated with an antimalarial medication prior to the third injection and prior to fourth injection.
They will be followed for approximately 6 months after third and fourth injection.
At vaccine visits, female participants will have a pregnancy test before injection. All participants will have an arm cleaned and the vaccine injected in a vein. They will be watched for 30 minutes.
At non-vaccine visits, participants will have a physical exam and be asked how they are feeling. They will usually have blood tests.
Read the detailed description
It is known that humans can be protected against malaria by repeated immunization with radiation-attenuated sporozoites. Sanaria, Inc. has developed a process for manufacturing, in compliance with current Good Manufacturing Practices (cGMPs) aseptic, purified, radiation- attenuated cryopreserved sporozoites from a well-characterized isolate of Plasmodium falciparum (Pf). This product, which is called PfSPZ Vaccine, can be administered by needle and syringe.
A collaboration among the Malaria Research and Training Center (MRTC, Mali), the Laboratory of Malaria Immunology and Vaccinology (LMIV) National Institute of Allergy and Infectious Diseases (NIAID), and Sanaria, Inc. has shown that sterile protection against naturally occurring malaria infection can be achieved. In this study, five doses of 2.7 x 10^5 PfSPZ during the dry season resulted in protective efficacies of about 48% by time to first positive blood smears (BS) and about 29% by proportion of participants with at least one positive BS during a full malaria transmission season (20 weeks), higher than those reported for other malaria vaccine candidates.
A follow up study in 2015 (ClinicalTrials.gov Identifier: NCT02627456) that reduced the number of vaccinations (from 5 to 3) while increasing the dose of sporozoites at each vaccination (2.7 x10^5 to 1.8x10^6 PfSPZ Vaccine) was conducted. Preliminary results show that 42 of 55 (77.8%) participants from the placebo group and 32 of 54 participants (58.1%) from the vaccine group developed Pf infection. Per protocol, the vaccine efficacy (VE) was 51% (p=0.004, 95% CI 20-70) by time-to-infection analysis (intention to treat (ITT) 39%, p=0.033) and 24% (p=0.031, 95% CI 2-41) by proportional analysis (ITT 22%, p= 0.041), similar to the previous study.
Studies are ongoing to establish a vaccination regimen, optimum dose and schedule, that will lead to improved sterile protection in endemic regions. Preliminary results from more recent studies in malaria-naïve and malaria-experienced participants have shown that 9.0x10^5 PfSPZ Vaccine dose per vaccination (lower than 1.8 x10^6 used in studies above) in a three-dose regimen may be an optimal dose for immunization. In addition, there is emerging evidence that a condensed, more practical regimen may also lead to development of sterile immunity. This proposed study is therefore designed to assess safety, immunogenicity and protective efficacy of two separate three-dose vaccination regimens during natural transmission season.
Participants in the main phase were randomized into arms receiving either PfSPZ Vaccine or normal saline injections. Each group received three doses of the respective injection during Year 1. After completion of the follow up in the main phase, all participants that are still enrolled in the study will be offered continued participation to receive a booster dose of the vaccine (dose # 4) with 9.0x10^5 PfSPZ or normal saline (depending on the group they were originally randomized to) at approximately 10 months post #3 vaccination. The booster dose is timed prior to ensuing malaria transmission season. Participants will be followed, similarly to the follow up during the main phase, for safety and vaccine efficacy for approximately 6 months during this second transmission season.
- Conditions
- Malaria
- Being tested
- PfSPZ Vaccine, Normal Saline, artemether 20mg/lumefantrine 120mg (AL)
- Keywords
- PfSPZ Vaccine, Malaria, Plasmodium falciparum
- 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 VaccineBiological
PfSPZ Vaccine is Radiation attenuated, aseptic, purified, vialed, cryopreserved, NF54 P. falciparum sporozoites produced by Sanaria, Inc.
Normal SalineDrug
Clear liquid indistinguishable from the study product will be used as a placebo rather than a comparator vaccine.
artemether 20mg/lumefantrine 120mg (AL)Drug
Also called Coartem
Licensed antimalarial in the US and Mali for use for uncomplicated malaria.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm 1: Dosing interval 0, 8, 16, and 54 weeks | Experimental | Participants received 3 doses of PfSPZ Vaccine (9 x 10^5) via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection. Receives: Biological: PfSPZ Vaccine; Drug: artemether 20mg/lumefantrine 120mg (AL) |
| Experimental arm 2: Dosing interval 0, 1, 4, and 42 weeks | Experimental | Participants received 3 doses of PfSPZ Vaccine (9 x 10^5) via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection. Receives: Biological: PfSPZ Vaccine; Drug: artemether 20mg/lumefantrine 120mg (AL) |
| Placebo comparator 3a: Dosing interval 0, 8, 16, and 54 weeks | Placebo comparator | Control for Arm 1. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection. Receives: Drug: Normal Saline; Drug: artemether 20mg/lumefantrine 120mg (AL) |
| Placebo comparator 3b: Dosing interval 0, 1, 4, and 42 weeks | Placebo comparator | Control for Arm 2. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection. Receives: Drug: Normal Saline; Drug: artemether 20mg/lumefantrine 120mg (AL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Local and Systemic Adverse Events in Year One
Incidence of local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine administration in year one
Measured: Within 7 days after each vaccination in year one
Number of Participants With Local and Systemic Adverse Events in Year Two
Incidence of local and systemic adverse events (AEs) graded by severity occurring within 7 days after vaccine administration during year two (booster dose)
Measured: Within 7 days after each vaccination in year two
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2018
- Study start14 May 2018
- Primary completion23 Nov 2019
- Study completion13 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 478 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Sanaria Inc., Malaria Research and Training Center, Bamako, Mali
- Responsible party
- Sponsor
- Investigators
- Patrick E Duffy, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03510481
- Sponsor's protocol ID
- 999918084
- Other IDs
- 18-I-N084
- Status last verified
- May 2021
- First submitted
- 26 Apr 2018
- Last updated
- 20 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Sissoko MS, Healy SA, Katile A, Omaswa F, Zaidi I, Gabriel EE, Kamate B, Samake Y, Guindo MA, Dolo A, Niangaly A, Niare K, Zeguime A, Sissoko K, Diallo H, Thera I, Ding K, Fay MP, O'Connell EM, Nutman TB, Wong-Madden S, Murshedkar T, Ruben AJ, Li M, Abebe Y, Manoj A, Gunasekera A, Chakravarty S, Sim BKL, Billingsley PF, James ER, Walther M, Richie TL, Hoffman SL, Doumbo O, Duffy PE. Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial. Lancet Infect Dis. 2017 May;17(5):498-509. doi: 10.1016/S1473-3099(17)30104-4. Epub 2017 Feb 16.
PubMed 28216244Jongo SA, Church LWP, Mtoro AT, Schindler T, Chakravarty S, Ruben AJ, Swanson PA, Kassim KR, Mpina M, Tumbo AM, Milando FA, Qassim M, Juma OA, Bakari BM, Simon B, James ER, Abebe Y, Kc N, Saverino E, Fink M, Cosi G, Gondwe L, Studer F, Styers D, Seder RA, Schindler T, Billingsley PF, Daubenberger C, Sim BKL, Tanner M, Richie TL, Abdulla S, Hoffman SL. Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults. Clin Infect Dis. 2020 Dec 31;71(11):2849-2857. doi: 10.1093/cid/ciz1152.
PubMed 31782768Diawara H, Healy SA, Mwakingwe-Omari A, Issiaka D, Diallo A, Traore S, Soumbounou IH, Gaoussou S, Zaidi I, Mahamar A, Attaher O, Fried M, Wylie BJ, Mohan R, Doan V, Doritchamou JYA, Dolo A, Morrison RD, Wang J, Hu Z, Rausch KM, Zeguime A, Murshedkar T, Kc N, Sim BKL, Billingsley PF, Richie TL, Hoffman SL, Dicko A, Duffy PE; PfSPZ Vaccine Study Team. Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials. Lancet Infect Dis. 2024 Dec;24(12):1366-1382. doi: 10.1016/S1473-3099(24)00360-8. Epub 2024 Aug 14.
PubMed 39153490
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety, Immunogenicity, and Protective Efficacy of Two Regimens of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Natural Transmission Season in Healthy African Adults in Mali
- ClinicalTrials.gov ID
- NCT03510481
- Acronym / sponsor ID
- 999918084
- Conditions
- Malaria
- Keywords
- PfSPZ Vaccine, Malaria, Plasmodium falciparum
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 478 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Sanaria Inc., Malaria Research and Training Center, Bamako, Mali
- Study start
- 14 May 2018 (actual)
- Primary completion
- 23 Nov 2019 (actual)
- Study completion
- 13 Feb 2020 (actual)
- First posted
- 27 Apr 2018 (actual)
- Results
- Posted 20 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
The disease malaria affects many people in Mali and other parts of Africa and the world. It is caused by germs spread by mosquito bites. Malaria may be mild. But it can also be serious or lead to death if it is not treated promptly. Researchers want to find a safe vaccine that prevents malaria.
Objective:
To study how safe and tolerable the malaria vaccine called PfSPZ Vaccine is for healthy adults.
Eligibility:
Healthy adults:
- ages 18-35 in Ouelessebougou, Mali
- not infected with HIV, hepatitis B, or hepatitis C
- for females, not pregnant or breastfeeding and must use reliable birth control during the study
Design:
Participants will be screened with questions about malaria and will undergo blood, urine, and heart tests.
Participants will be randomly assigned to 1 of 4 groups. They will get injections of either the PfSPZ Vaccine or a salt-water placebo. They will not know which one they get.
Vaccinations will occur leading into the malaria transmission each year with 3 injections leading into Year 1 (malaria transmission season in 2018) and 1 injection prior to Year 2 (malaria transmission season 2019).
One vaccine group and one placebo group will get an injection 3 times over 4 weeks with an additional vaccination ~10 months later.
The other two groups (vaccine group and placebo) will get an injection 3 times over 16 weeks with an additional vaccination ~10 months later.
All participants will be treated with an antimalarial medication prior to the third injection and prior to fourth injection.
They will be followed for approximately 6 months after third and fourth injection.
At vaccine visits, female participants will have a pregnancy test before injection. All participants will have an arm cleaned and the vaccine injected in a vein. They will be watched for 30 minutes.
At non-vaccine visits, participants will have a physical exam and be asked how they are feeling. They will usually have blood tests.
Detailed description
It is known that humans can be protected against malaria by repeated immunization with radiation-attenuated sporozoites. Sanaria, Inc. has developed a process for manufacturing, in compliance with current Good Manufacturing Practices (cGMPs) aseptic, purified, radiation- attenuated cryopreserved sporozoites from a well-characterized isolate of Plasmodium falciparum (Pf). This product, which is called PfSPZ Vaccine, can be administered by needle and syringe.
A collaboration among the Malaria Research and Training Center (MRTC, Mali), the Laboratory of Malaria Immunology and Vaccinology (LMIV) National Institute of Allergy and Infectious Diseases (NIAID), and Sanaria, Inc. has shown that sterile protection against naturally occurring malaria infection can be achieved. In this study, five doses of 2.7 x 10^5 PfSPZ during the dry season resulted in protective efficacies of about 48% by time to first positive blood smears (BS) and about 29% by proportion of participants with at least one positive BS during a full malaria transmission season (20 weeks), higher than those reported for other malaria vaccine candidates.
A follow up study in 2015 (ClinicalTrials.gov Identifier: NCT02627456) that reduced the number of vaccinations (from 5 to 3) while increasing the dose of sporozoites at each vaccination (2.7 x10^5 to 1.8x10^6 PfSPZ Vaccine) was conducted. Preliminary results show that 42 of 55 (77.8%) participants from the placebo group and 32 of 54 participants (58.1%) from the vaccine group developed Pf infection. Per protocol, the vaccine efficacy (VE) was 51% (p=0.004, 95% CI 20-70) by time-to-infection analysis (intention to treat (ITT) 39%, p=0.033) and 24% (p=0.031, 95% CI 2-41) by proportional analysis (ITT 22%, p= 0.041), similar to the previous study.
Studies are ongoing to establish a vaccination regimen, optimum dose and schedule, that will lead to improved sterile protection in endemic regions. Preliminary results from more recent studies in malaria-naïve and malaria-experienced participants have shown that 9.0x10^5 PfSPZ Vaccine dose per vaccination (lower than 1.8 x10^6 used in studies above) in a three-dose regimen may be an optimal dose for immunization. In addition, there is emerging evidence that a condensed, more practical regimen may also lead to development of sterile immunity. This proposed study is therefore designed to assess safety, immunogenicity and protective efficacy of two separate three-dose vaccination regimens during natural transmission season.
Participants in the main phase were randomized into arms receiving either PfSPZ Vaccine or normal saline injections. Each group received three doses of the respective injection during Year 1. After completion of the follow up in the main phase, all participants that are still enrolled in the study will be offered continued participation to receive a booster dose of the vaccine (dose # 4) with 9.0x10^5 PfSPZ or normal saline (depending on the group they were originally randomized to) at approximately 10 months post #3 vaccination. The booster dose is timed prior to ensuing malaria transmission season. Participants will be followed, similarly to the follow up during the main phase, for safety and vaccine efficacy for approximately 6 months during this second transmission season.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Experimental arm 1: Dosing interval 0, 8, 16, and 54 weeks | Experimental | Biological: PfSPZ Vaccine, Drug: artemether 20mg/lumefantrine 120mg (AL)Participants received 3 doses of PfSPZ Vaccine (9 x 10^5) via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection. |
| Experimental arm 2: Dosing interval 0, 1, 4, and 42 weeks | Experimental | Biological: PfSPZ Vaccine, Drug: artemether 20mg/lumefantrine 120mg (AL)Participants received 3 doses of PfSPZ Vaccine (9 x 10^5) via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection. |
| Placebo comparator 3a: Dosing interval 0, 8, 16, and 54 weeks | Placebo comparator | Drug: Normal Saline, Drug: artemether 20mg/lumefantrine 120mg (AL)Control for Arm 1. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection. |
| Placebo comparator 3b: Dosing interval 0, 1, 4, and 42 weeks | Placebo comparator | Drug: Normal Saline, Drug: artemether 20mg/lumefantrine 120mg (AL)Control for Arm 2. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
Key exclusion criteria (25 listed)
- Pregnancy, as determined by a positive urine or serum human chorionic gonadotropin (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 (Hb), WBC, absolute neutrophils, and platelets outside the local laboratory- defined 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 laboratory-defined upper limit of normal (subjects may be included at the investigator s discretion for not clinically significant values)
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 VaccinePfSPZ Vaccine is Radiation attenuated, aseptic, purified, vialed, cryopreserved, NF54 P. falciparum sporozoites produced by Sanaria, Inc. | Biological | Experimental arm 1: Dosing interval 0, 8, 16, and 54 weeks, Experimental arm 2: Dosing interval 0, 1, 4, and 42 weeks |
| Normal SalineClear liquid indistinguishable from the study product will be used as a placebo rather than a comparator vaccine. | Drug | Placebo comparator 3a: Dosing interval 0, 8, 16, and 54 weeks, Placebo comparator 3b: Dosing interval 0, 1, 4, and 42 weeks |
| artemether 20mg/lumefantrine 120mg (AL)Also: CoartemLicensed antimalarial in the US and Mali for use for uncomplicated malaria. | Drug | Experimental arm 1: Dosing interval 0, 8, 16, and 54 weeks, Experimental arm 2: Dosing interval 0, 1, 4, and 42 weeks, Placebo comparator 3a: Dosing interval 0, 8, 16, and 54 weeks, Placebo comparator 3b: Dosing interval 0, 1, 4, and 42 weeks |
Primary outcome
Number of Participants With Local and Systemic Adverse Events in Year One
Time frame: Within 7 days after each vaccination in year one
Incidence of local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine administration in year one
Number of Participants With Local and Systemic Adverse Events in Year Two
Time frame: Within 7 days after each vaccination in year two
Incidence of local and systemic adverse events (AEs) graded by severity occurring within 7 days after vaccine administration during year two (booster dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28216244Sissoko MS, Healy SA, Katile A, Omaswa F, Zaidi I, Gabriel EE, Kamate B, Samake Y, Guindo MA, Dolo A, Niangaly A, Niare K, Zeguime A, Sissoko K, Diallo H, Thera I, Ding K, Fay MP, O'Connell EM, Nutman TB, Wong-Madden S, Murshedkar T, Ruben AJ, Li M, Abebe Y, Manoj A, Gunasekera A, Chakravarty S, Sim BKL, Billingsley PF, James ER, Walther M, Richie TL, Hoffman SL, Doumbo O, Duffy PE. Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial. Lancet Infect Dis. 2017 May;17(5):498-509. doi: 10.1016/S1473-3099(17)30104-4. Epub 2017 Feb 16.
- Background: PubMed 31782768Jongo SA, Church LWP, Mtoro AT, Schindler T, Chakravarty S, Ruben AJ, Swanson PA, Kassim KR, Mpina M, Tumbo AM, Milando FA, Qassim M, Juma OA, Bakari BM, Simon B, James ER, Abebe Y, Kc N, Saverino E, Fink M, Cosi G, Gondwe L, Studer F, Styers D, Seder RA, Schindler T, Billingsley PF, Daubenberger C, Sim BKL, Tanner M, Richie TL, Abdulla S, Hoffman SL. Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults. Clin Infect Dis. 2020 Dec 31;71(11):2849-2857. doi: 10.1093/cid/ciz1152.
- Derived from this study: PubMed 39153490Diawara H, Healy SA, Mwakingwe-Omari A, Issiaka D, Diallo A, Traore S, Soumbounou IH, Gaoussou S, Zaidi I, Mahamar A, Attaher O, Fried M, Wylie BJ, Mohan R, Doan V, Doritchamou JYA, Dolo A, Morrison RD, Wang J, Hu Z, Rausch KM, Zeguime A, Murshedkar T, Kc N, Sim BKL, Billingsley PF, Richie TL, Hoffman SL, Dicko A, Duffy PE; PfSPZ Vaccine Study Team. Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials. Lancet Infect Dis. 2024 Dec;24(12):1366-1382. doi: 10.1016/S1473-3099(24)00360-8. Epub 2024 Aug 14.
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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.
Patrick E Duffy, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site 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 Vaccine, Normal Saline and artemether 20mg/lumefantrine 120mg (AL) in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
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 11 inclusion and 25 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 20 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mali. 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?
Yes. Results are posted in the registry (first posted 20 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Local and Systemic Adverse Events in Year One (time frame: Within 7 days after each vaccination in year one). 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 NCT03510481, which also lists 3 linked publications.
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 20 Aug 2021.