MalariaPhase 2NCT04940130
PfSPZ Vaccine Trial in Malian Children
A Phase 2 study testing Sanaria® PfSPZ Vaccine and Normal Saline in people with Malaria and Malaria,Falciparum, run by Sanaria Inc. at 1 site in Mali.
Trial summary
In this randomized, double-blind, placebo-controlled trial, 268 healthy Malian children aged 6-10 years, residing in Bancoumana and surrounding villages, will be administered three doses of 9.0x10^5 Pf sporozoites (PfSPZ) of PfSPZ Vaccine (or placebo) at 1, 8, and 29-days using direct venous inoculation (DVI). Read more about this study
- Who is it for?
- Ages 6 to 10 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Malaria,Falciparum
- What is being tested?
- Sanaria® PfSPZ Vaccine and Normal Saline
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 290 participants
- Where
- 1 siteMali
- Study dates
- 1 Apr 2022to 10 Dec 2022
- Phase
- Phase 2
- 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 6 to 10 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Parent(s) or guardian(s) willing and able to provide consent prior to initiation of any study procedures
- Stated willingness of parent(s) or guardian(s) to comply with all study procedures and availability for the duration of the study
- Malaria comprehension exam completed by parent(s) or guardian(s) and passed with a score of ≥80% or per investigator's discretion
- Healthy children 6-10 years of age at enrollment (inclusive)
- Parent(s) or guardian(s) are 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
Who cannot join
- Medical, behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant's parent and/or legal guardian to understand and comply with the study protocol
- Menstruating females (in order to avoid cultural implications of further assessing pregnancy potential i.e. sexual activity in this age group)
- Hemoglobin (Hgb), WBC, absolute neutrophils, and platelets outside the local laboratory-defined limits of normal and ≥ Grade 2 (subjects may be included at the investigator's discretion for 'not clinically significant' abnormal values)
- Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal and ≥ Grade 2 (subjects may be included at the investigator's discretion for 'not clinically significant' abnormal values)
- Infected with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
- Sickle cell disease by history
Show all 24Show fewer
- Taking or planning to take seasonal malaria chemoprophylaxis
- Clinically significant abnormal electrocardiogram (ECG) such as abnormal QTc
- History of receipt of the following:
- Investigational malaria vaccine in the last 2 years
- Immunoglobulins and/or blood products within 6 months of enrollment
- Investigational product within 3 months of enrollment
- Chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone ≥20 mg/day or equivalent) or immunosuppressive drugs within 30 days of enrollment
- Live vaccine within 30 days of enrollment
- Killed vaccine within 14 days of enrollment or planned receipt of a killed vaccine within 14 days of scheduled vaccination
- Known medical problems:
- Pre-existing autoimmune or antibody-mediated diseases (e.g. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia)
- 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)
- Immunodeficiency disorder
- Asplenia or functional asplenia
- Diabetes
- Deep venous thrombosis or thromboembolic event
- Seizures (exception is simple febrile seizures during childhood)
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Trial of Safety, Immunogenicity, and Efficacy Against Plasmodium Falciparum Malaria of PfSPZ Vaccine in Children in Mali
In this randomized, double-blind, placebo-controlled trial, 268 healthy Malian children aged 6-10 years, residing in Bancoumana and surrounding villages, will be administered three doses of 9.0x10^5 Pf sporozoites (PfSPZ) of PfSPZ Vaccine (or placebo) at 1, 8, and 29-days using direct venous inoculation (DVI).
The study is composed of a single cohort with two arms (categorized by placebo control/experimental groups) designed to assess the safety, immunogenicity and protective efficacy of PfSPZ Vaccine.
All subjects will receive artemether-lumefantrine (AL) approximately 1- 2 weeks before the first dose of PfSPZ Vaccine or normal saline for clearance of Pf parasitemia. Vaccinated participants and non-immunized controls will be followed for safety and monitored for development of parasitemia through the natural malaria transmission season to estimate vaccine efficacy (VE).
Read the detailed description
This phase 2 study will enroll healthy Malian children between 6 and 10 years of age residing in Bancoumana and surrounding villages to participate in a randomized, double blind, placebo- controlled study to assess the safety, immunogenicity and protective efficacy of PfSPZ Vaccine.
Participants will be immunized with a 3-dose series of 9.0 x10^5 PfSPZ of PfSPZ Vaccine or normal saline (placebo) at 1, 8, and 29 days. Subjects will be screened for eligibility for enrollment. Enrollment will begin with AL dosing approximately 1-2 weeks prior to their first dose of vaccine. Volunteers will be randomized into two arms (1 vaccine arm, 1 control arm) in a 1:1 ratio.
Vaccinated subjects and controls will then be followed for safety and assessment for malaria infection during the subsequent malaria transmission season.
268 children between the ages of 6 and 10 years old inclusive will be enrolled as follows:
Arm 1(PfSPZ Vaccine): (n = 134) children ages 6 - 10 will receive three doses of PfSPZ Vaccine (9.0x10^5 PfSPZ) via direct venous inoculation (DVI) at 1, 8, and 29 days
Arm 2 (normal saline): (n = 134) children ages 6 - 10 will receive normal saline via DVI at 1, 8, and 29 days All subjects will receive artemether-lumefantrine (AL) approximately 1- 2 weeks before the first dose of PfSPZ Vaccine or normal saline for clearance of Pf parasitemia.
Vaccinated participants and non-vaccinated controls will be monitored for development of Pf malaria with symptoms and Pf malaria (parasitemia) through the natural malaria transmission season to estimate vaccine efficacy (VE). During the surveillance period, both active and passive surveillance will be used to identify Pf malaria with symptoms. Blood smears will be made at any time a participant presents with a clinical syndrome consistent with malaria and read in real time, with all infections treated.
In addition, blood smears will be made every four weeks in all participants as active surveillance for Pf malaria (parasitemia). However, to avoid confounding the primary clinical endpoint, these blood smears will be read retrospectively at the end of the primary surveillance period.
Primary Case Definition:
Pf malaria with symptoms is defined as a positive thick blood smear at a density of >1000 parasites/uL (P/uL) plus:
- Measured auxiliary temperature ≥ 37.5 degrees Celsius or history of fever (subjective or objective) in the last 24 hours, or,
- Symptoms of malaria -
- Verbal individual (individual able and willing to answer questions): A verbal individual is considered symptomatic if reporting at the time of evaluation at least two of the following symptoms/symptom groups: headache, chills and/or rigors, malaise and/or fatigue, dizziness and/or light-headedness, myalgias and/or arthralgias; or
- Non-verbal individual (small child or any individual unable or unwilling to answer questions): A non-verbal individual is considered symptomatic if manifesting at the time of evaluation at least two of the following signs/sign groups: drowsiness, irritability and/or fussiness, inability and/or refusal to eat or drink, prostration; or
- Any individual: Signs of severe malaria (e.g. impairment of consciousness, severe anemia, hemoglobinuria, acute kidney injury, etc.)
Secondary Case Definition:
Pf malaria with symptoms is defined as a positive thick blood smear at a density of > 0 P/uL plus:
- Measured axillary temperature ≥ 37.5 degrees Celsius or history of fever (subjective or objective) in the last 24 hours, or,
- Symptoms of malaria as defined in the primary case definition; or
- Meeting criteria for severe malaria
Pf malaria is defined as:
- At least one unambiguous asexual parasite on thick blood smear identified by two independent microscopists after each examining 0.50 μL of blood in a study participant
- Conditions
- Malaria, Malaria,Falciparum
- Being tested
- Sanaria® PfSPZ Vaccine, Normal Saline
- 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.
Sanaria® PfSPZ VaccineBiological
non-adjuvanted, live (metabolically active), radiation-attenuated, non-replicating, whole sporozoite (SPZ) vaccine designed to prevent malaria infection caused by Plasmodium falciparum (Pf).
Normal SalineOther
placebo control- saline
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (PfSPZ Vaccine) | Experimental | 134 children ages 6 - 10 will receive three doses of PfSPZ Vaccine (9.0x10^5 PfSPZ) via DVI at 1, 8, and 29 days Receives: Biological: Sanaria® PfSPZ Vaccine |
| Arm 2 (normal saline) | Placebo comparator | 134 children ages 6 - 10 will receive normal saline via DVI at 1, 8, and 29 days Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Possibly, Probably, or Definitely Related Serious Adverse Events (SAEs)
Proportion of vaccinees compared to controls experiencing related SAEs from V1 to 26 weeks after V3
Measured: From day of first vaccination until 26 weeks after 3rd vaccination (study day 1 to day 211)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2021
- Study start1 Apr 2022
- Primary completion10 Dec 2022
- Study completion10 Dec 2022
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.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, placebo controlled, with concurrent arms
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 290 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanaria Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Malaria Research and Training Center, Bamako, Mali, University of the Sciences, Techniques and Technologies of Bamako, National Institute of Allergy and Infectious Diseases (NIAID)
- Responsible party
- Sponsor
- Investigators
- Patrick Duffy, MD, Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)Issaka Sagara, MD MSPH PhD, Principal investigator, Malaria Research and Training Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04940130
- Sponsor's protocol ID
- MLSPZV5
- Status last verified
- Dec 2023
- First submitted
- 3 Jun 2021
- Last updated
- 7 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Safety, Immunogenicity, and Efficacy Against Plasmodium Falciparum Malaria of PfSPZ Vaccine in Children in Mali
- ClinicalTrials.gov ID
- NCT04940130
- Acronym / sponsor ID
- MLSPZV5
- Conditions
- Malaria, Malaria,Falciparum
- Keywords
- PfSPZ Vaccine, Malaria, Plasmodium falciparum
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 290 participants (actual)
- Lead sponsor
- Sanaria Inc.Industry (pharma, biotech, devices)
- Collaborators
- Malaria Research and Training Center, Bamako, Mali, University of the Sciences, Techniques and Technologies of Bamako, National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- 10 Dec 2022 (actual)
- Study completion
- 10 Dec 2022 (actual)
- First posted
- 25 Jun 2021 (actual)
- Results
- Posted 7 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this randomized, double-blind, placebo-controlled trial, 268 healthy Malian children aged 6-10 years, residing in Bancoumana and surrounding villages, will be administered three doses of 9.0x10^5 Pf sporozoites (PfSPZ) of PfSPZ Vaccine (or placebo) at 1, 8, and 29-days using direct venous inoculation (DVI).
The study is composed of a single cohort with two arms (categorized by placebo control/experimental groups) designed to assess the safety, immunogenicity and protective efficacy of PfSPZ Vaccine.
All subjects will receive artemether-lumefantrine (AL) approximately 1- 2 weeks before the first dose of PfSPZ Vaccine or normal saline for clearance of Pf parasitemia. Vaccinated participants and non-immunized controls will be followed for safety and monitored for development of parasitemia through the natural malaria transmission season to estimate vaccine efficacy (VE).
Detailed description
This phase 2 study will enroll healthy Malian children between 6 and 10 years of age residing in Bancoumana and surrounding villages to participate in a randomized, double blind, placebo- controlled study to assess the safety, immunogenicity and protective efficacy of PfSPZ Vaccine.
Participants will be immunized with a 3-dose series of 9.0 x10^5 PfSPZ of PfSPZ Vaccine or normal saline (placebo) at 1, 8, and 29 days. Subjects will be screened for eligibility for enrollment. Enrollment will begin with AL dosing approximately 1-2 weeks prior to their first dose of vaccine. Volunteers will be randomized into two arms (1 vaccine arm, 1 control arm) in a 1:1 ratio.
Vaccinated subjects and controls will then be followed for safety and assessment for malaria infection during the subsequent malaria transmission season.
268 children between the ages of 6 and 10 years old inclusive will be enrolled as follows:
Arm 1(PfSPZ Vaccine): (n = 134) children ages 6 - 10 will receive three doses of PfSPZ Vaccine (9.0x10^5 PfSPZ) via direct venous inoculation (DVI) at 1, 8, and 29 days
Arm 2 (normal saline): (n = 134) children ages 6 - 10 will receive normal saline via DVI at 1, 8, and 29 days All subjects will receive artemether-lumefantrine (AL) approximately 1- 2 weeks before the first dose of PfSPZ Vaccine or normal saline for clearance of Pf parasitemia.
Vaccinated participants and non-vaccinated controls will be monitored for development of Pf malaria with symptoms and Pf malaria (parasitemia) through the natural malaria transmission season to estimate vaccine efficacy (VE). During the surveillance period, both active and passive surveillance will be used to identify Pf malaria with symptoms. Blood smears will be made at any time a participant presents with a clinical syndrome consistent with malaria and read in real time, with all infections treated.
In addition, blood smears will be made every four weeks in all participants as active surveillance for Pf malaria (parasitemia). However, to avoid confounding the primary clinical endpoint, these blood smears will be read retrospectively at the end of the primary surveillance period.
Primary Case Definition:
Pf malaria with symptoms is defined as a positive thick blood smear at a density of >1000 parasites/uL (P/uL) plus:
- Measured auxiliary temperature ≥ 37.5 degrees Celsius or history of fever (subjective or objective) in the last 24 hours, or,
- Symptoms of malaria -
- Verbal individual (individual able and willing to answer questions): A verbal individual is considered symptomatic if reporting at the time of evaluation at least two of the following symptoms/symptom groups: headache, chills and/or rigors, malaise and/or fatigue, dizziness and/or light-headedness, myalgias and/or arthralgias; or
- Non-verbal individual (small child or any individual unable or unwilling to answer questions): A non-verbal individual is considered symptomatic if manifesting at the time of evaluation at least two of the following signs/sign groups: drowsiness, irritability and/or fussiness, inability and/or refusal to eat or drink, prostration; or
- Any individual: Signs of severe malaria (e.g. impairment of consciousness, severe anemia, hemoglobinuria, acute kidney injury, etc.)
Secondary Case Definition:
Pf malaria with symptoms is defined as a positive thick blood smear at a density of > 0 P/uL plus:
- Measured axillary temperature ≥ 37.5 degrees Celsius or history of fever (subjective or objective) in the last 24 hours, or,
- Symptoms of malaria as defined in the primary case definition; or
- Meeting criteria for severe malaria
Pf malaria is defined as:
- At least one unambiguous asexual parasite on thick blood smear identified by two independent microscopists after each examining 0.50 μL of blood in a study participant
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- randomized, placebo controlled, with concurrent arms
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (PfSPZ Vaccine) | Experimental | Biological: Sanaria® PfSPZ Vaccine134 children ages 6 - 10 will receive three doses of PfSPZ Vaccine (9.0x10^5 PfSPZ) via DVI at 1, 8, and 29 days |
| Arm 2 (normal saline) | Placebo comparator | Other: Normal Saline134 children ages 6 - 10 will receive normal saline via DVI at 1, 8, and 29 days |
Who may qualify
- Ages
- 6 to 10 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Parent(s) or guardian(s) willing and able to provide consent prior to initiation of any study procedures
- Stated willingness of parent(s) or guardian(s) to comply with all study procedures and availability for the duration of the study
- Malaria comprehension exam completed by parent(s) or guardian(s) and passed with a score of ≥80% or per investigator's discretion
- Healthy children 6-10 years of age at enrollment (inclusive)
- Parent(s) or guardian(s) are able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
Key exclusion criteria (24 listed)
- Medical, behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant's parent and/or legal guardian to understand and comply with the study protocol
- Menstruating females (in order to avoid cultural implications of further assessing pregnancy potential i.e. sexual activity in this age group)
- Hemoglobin (Hgb), WBC, absolute neutrophils, and platelets outside the local laboratory-defined limits of normal and ≥ Grade 2 (subjects may be included at the investigator's discretion for 'not clinically significant' abnormal values)
- Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal and ≥ Grade 2 (subjects may be included at the investigator's discretion for 'not clinically significant' abnormal values)
- Infected with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
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 |
|---|---|---|
| Sanaria® PfSPZ Vaccinenon-adjuvanted, live (metabolically active), radiation-attenuated, non-replicating, whole sporozoite (SPZ) vaccine designed to prevent malaria infection caused by Plasmodium falciparum (Pf). | Biological | Arm 1 (PfSPZ Vaccine) |
| Normal Salineplacebo control- saline | Other | Arm 2 (normal saline) |
Primary outcome
Number of Participants With Possibly, Probably, or Definitely Related Serious Adverse Events (SAEs)
Time frame: From day of first vaccination until 26 weeks after 3rd vaccination (study day 1 to day 211)
Proportion of vaccinees compared to controls experiencing related SAEs from V1 to 26 weeks after V3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Patrick Duffy, MD principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
Issaka Sagara, MD MSPH PhD principal investigator
Malaria Research and Training Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sanaria® PfSPZ Vaccine and Normal Saline in people with Malaria and Malaria,Falciparum, run by Sanaria Inc. 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 6 inclusion and 24 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 7 Feb 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 7 Feb 2024). 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 Possibly, Probably, or Definitely Related Serious Adverse Events (SAEs) (time frame: From day of first vaccination until 26 weeks after 3rd vaccination (study day 1 to day 211)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Feb 2024.