CompletedNCT02942277Updated Dec 10, 2024Results posted

Safety and Immunogenicity of Pfs25M-EPA/AS01 and Pfs230D1M-EPA/AS01 Vaccines, Transmission Blocking Vaccines Against Plasmodium Falciparum, at Full and Fractional Dosing in Adults in Mali

A Phase 1 interventional study of Pfs25M-EPA and Pfs230D1M-EPA in Malaria, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 1 site in Mali. Open to participants aged 18 Years to 52 Years. Per ClinicalTrials.gov, last updated 2024-12-10.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Prevention

Phase: Phase 1
Study type: Interventional
Enrollment: 301
Allocation: Randomized
Ages: 18 Years to 52 Years
Sex: All

Study summary

Background:

Researchers are looking for new ways to control and eradicate malaria. They want to test vaccines to block malaria transmission in adults in Mali. These vaccines work by inducing antibodies in a person. The antibody is then taken up with blood by a mosquito that bites the person. This blocks parasite development in the mosquito. This stops malaria transmission to another person.

Objective:

To test the safety, reactogenicity, immunogenicity, and transmission-blocking activity of the vaccines Pfs25M-EPA and Pfs230D1M-EPA with AS01 in Malian adults.

Eligibility:

Healthy Malians ages 18-50 living in certain areas in Mali who:

Are not pregnant or breastfeeding

Are not infected with HIV, Hepatitis B and Hepatitis C

Do not have evidence of immunodeficiency

Do not have history of severe allergic reaction or anaphylaxis

Design:

Participants will be screened with:

Medical history

Physical exam

Malaria Comprehension Exam

Blood and urine tests

Electrocardiogram (for participants in certain study groups)

Participants will be randomly assigned to a study group.

Participants will be monitored for 12-16 months. For the first 7 months, they will have between 1 and nine visits a month. The number depends on the month and on what group they are in. For the rest of the months, they will have 1 monthly visit.

Each visit includes a physical exam. Most include blood tests.

Participants will get 3 doses of a study or comparator vaccine. They get the vaccine through an injection in the upper arm. This occurs at their first visit, then 1 month later, and then 5 months later.

Participants will be followed for at least 6 months after the last vaccine.

If participants develop an injection site rash or reaction, photographs may be taken of the site.

Read the detailed description

A vaccine to interrupt malaria transmission (VIMT) would be a valuable tool for local elimination or eradication of this disease, and may contain components that block transmission to mosquitoes (such as Pfs25 or Pfs230) or that prevent human infection (such as the vaccine RTS,S). Pfs25 and Pfs230, surface antigens of zygotes and ookinetes (and gametocytes for Pfs230) in the mosquito stage of P. falciparum, are the lead candidates for a malaria transmission blocking vaccine (TBV). Recombinant Pfs25M and recombinant Pfs230D1M have each been conjugated to P. aeruginosa ExoProtein A (EPA) and adjuvanted with AS01. Our ongoing experience with Pfs25M-EPA and Pfs230D1M-EPA in Malian adult trial participants, and the extensive experience with the AS01 adjuvants in African children and adults, justify conducting the first-in-human trial of Pfs25M-EPA and Pfs230D1M-EPA with AS01 in Malian adults. This dose-escalating phase 1 study will determine safety, immunogenicity, and functional activity of these vaccines in Malian adults. Pfs25M-EPA + Pfs230D1M-EPA in AS01 will be assessed by mosquito feeding assays in Malian adults for evidence that they may reduce the number of malaria transmission events in study subjects.

A total of 305 subjects will be enrolled at multiple sites in Mali, West Africa to receive escalating doses of a malaria transmission blocking vaccine (s): Pfs25M-EPA/AS01, Pfs230D1M-EPA/AS01, or simultaneous administration of Pfs25M-EPA/AS01 and Pfs230D1M-EPA/AS01; or a comparator vaccine (ENERGIX-B). Enrollment within each group will be staggered for additional safety and subjects will only be enrolled into the co-administration group once each individual dose has been administered. Subjects will be followed for at least 6 months after the last vaccination. Safety outcomes will be local and systemic adverse events and serious adverse events. Immunogenicity outcomes will be antibody responses as measured by ELISA against recombinant Pfs25, Pfs230, EPA, CSP, and B cell and T cell responses. Functional activity of the induced antibodies will be assessed in TBV arms by standard membrane feeding assays conducted at the National Institute of Allergy and Infectious Diseases, and activity that interrupts malaria transmission will be measured in all arms by direct skin feeding assays in Mali.

Subjects in the open label safety cohorts (Arms 1a, 1b, 2a, 2b, 3a, 3b, 4a, 4b) will be offered reenrollment for follow-up laboratory assessment to explore the duration of immunogenicity and functional activity at approximately 9, 12 months post vaccination. Following scheduled, intentional unblinding, subjects enrolled in Arms 2c, 2d, and 4c will be provided the opportunity to re-enroll for a fourth vaccination (Arm 2c and 2d with 40 microgram dose of Pfs230D1M-EPA/AS01; Arm 4c with Menatctra) approximately 1 year post vaccination #3. Subjects in these arms will also be eligible to re-enroll for follow up of duration of immunogenicity and functional activity at approximately 9, 12 months post vaccination if they choose not to enroll to recive the booster vaccination. Subjects will be followed similarly to the previous year for safety, immunogenicity, and functional activity.

Conditions studied

Malaria

Browse trials for

Malaria 1,315

Keywords

Malaria
Reactogenicity
Antibody
Direct Skin Feed
Mosquito

In context

Malaria

1,315 studies on the registry are indexed under Malaria; 86 are open to participants now.

This study's enrollment of 301 is above the median of 220 across 1,041 interventional studies indexed under Malaria.

Browse Malaria studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,445 studies on the registry; 182 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 300 (75%) have results posted.

Browse National Institute of Allergy and Infectious Diseases (NIAID) studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 52 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Age greater than or equal to 18 and less than or equal to 50 years.
Available for the duration of the trial.
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 in the opinion of the investigator.
Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to Study Day 0 (Study Day 476 for re-enrollment) and then until 3 months after last vaccination.
- Reliable methods of birth control include one of the following: confirmed pharmacologic contraceptives (parenteral) delivery; intrauterine or implantable device.
- Reliable methods of birth control include concurrent use of a pharmacologic and a barrier method, i.e. two of the following: confirmed pharmacologic contraceptives (oral, transdermal) delivery or vaginal ring AND condoms with spermicide or diaphragm with spermicide.
- Non-childbearing women will also be required to report date of last menstrual period, history of surgical sterility (i.e. tubal ligation, hysterectomy) or premature ovarian insufficiency (POI), and will have a baseline urine or serum pregnancy test performed.
Willingness to have blood samples stored for future research.
Willingness to undergo DSFs (Arms 3c, 3d, 4c only).
Known resident of Bancoumana or Doneguebougou or surrounding area or known student or long term resident (more than 1 year) of Bamako/Sotuba, Mali

Exclusion criteria

EXCLUSION CRITERIA:

Pregnancy as determined by a positive urine or serum human choriogonadotropin (beta-hCG) test (if female).
NOTE: Pregnancy is also a criteria for discontinuation of any further dosing or non-safety related interventions for that subject.
Currently breast-feeding (if female).
Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol.
Hemoglobin, WBC, absolute neutrophils, and platelets outside the local laboratory-defined limits of normal (subjects may be included at the investigator s discretion for not clinically significant values outside of normal range and less than or equal to Grade 1).
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 outside of normal range and less than or equal to Grade 1).
Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B (HBV).
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
Subject has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
History of a severe allergic reaction or anaphylaxis.
Severe asthma, defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years.
Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sj(SqrRoot)(Delta)gren 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 intravenous corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of Study Day 0.
Prior to Study Day 0 and every subsequent vaccination day, receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks.
Receipt of immunoglobulins and/or blood products within the past 6 months.
Previous receipt of an investigational malaria vaccine in the last 5 years.
History of severe reaction to mosquito bites (Arms 3c, 3d, 4c only)
History of allergy to the comparator vaccine (such as latex, yeast, or previous Hepatitis B vaccine)
Known allergies or contraindications (such as significant cardiac disease; prolonged QTc >450 ms; currently taking medications that may prolong your QTc; serious side effects from Coartem in the past) to study treatment (Coartem [artemether/lumefantrine]) (Arms 3c, 3d, 4c only)
Other condition 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.

Study design

Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 301 participants (actual)

Study arms

Experimental
1a
(n=5), to receive 16 microgram Pfs25M-EPA/AS01 on D0, D28, D168
Biological: Pfs25M-EPA · Other: AS01 · Other: Normal Saline
Experimental
1b
(n=10), to receive 47 microgram Pfs25M-EPA/AS01 on D0, D28, D168
Biological: Pfs25M-EPA · Other: AS01
Experimental
2a
(n=5), to receive 13 microgram Pfs230D1M-EPA/AS01 on D0, D28, D168
Biological: Pfs230D1M-EPA · Other: AS01 · Other: Normal Saline
Experimental
2b
(n=10), to receive 40 microgram Pfs230D1M-EPA/AS01 on D0, D28, D168
Biological: Pfs230D1M-EPA · Other: AS01
Experimental
2c
(n=60), to receive 40 micrograms Pfs230D1M-EPA/AS01 on D0, D28, D168; all subjects will undergo antimalarial drug treatment with Coartem on D-7 (prior to vaccination #1); 4th vaccination on D476
Biological: Pfs230D1M-EPA · Other: AS01 · Drug: Coartem
Experimental
2d
(n=60), to receive 40 micrograms Pfs230D1M-EPA/AS01 (500 (Micro)L TBV + AS01) on D0, D28, then 8 micro liters Pfs230D1M- EPA/AS01 (100 (Micro)L TBV + AS01;fractional dose) on D168; all subjects will undergo antimalarial drug treatment with Coartem on D-7 (prior to vaccination #1); 4th vaccination on D476
Biological: Pfs230D1M-EPA · Other: AS01 · Drug: Coartem
Experimental
3a
(n=5), to receive 16 microgram Pfs25M-EPA/AS01 and 13 microgram Pfs230D1M-EPA/AS01 on D0, D28, D168
Biological: Pfs25M-EPA · Biological: Pfs230D1M-EPA · Other: AS01 · Other: Normal Saline
Experimental
3b
(n=10), to receive 47 microgram Pfs25M-EPA/AS01 and 40 microgram Pfs230D1M-EPA/AS01 on D0, D28, D168 (Bamako)
Biological: Pfs25M-EPA · Biological: Pfs230D1M-EPA · Other: AS01
Active comparator
4a
(n=10), to receive ENGERIX-B on D0, D28, and D168
Biological: Engerix-B · Other: Normal Saline
Active comparator
4b
(n=10), to receive ENGERIX-B on DO, D28, and Dl68
Biological: Engerix-B · Drug: Coartem
Active comparator
4c
(n=120), to receive ENGERIX-B on D0, D28, and D168 (start study with Arm 2c and 2d); all subjects will undergo antimalarial drug treatment with Coartem on D-7 (prior to vaccination #1); vaccination with Menactra on D476
Biological: Engerix-B · Biological: Menactra · Drug: Coartem

Interventions

BiologicalPfs25M-EPA
The PpPfs25M and EcEPA lots, both manufactured at Walter Reed Bioproduction facility (Silver Spring, Maryland) in cGMP compliance, were used to manufacture the conjugate. PpPfs25M is a Pichia- expressed recombinant Pfs25 with a molecular mass of 18,713 Daltons.The Pfs25M- EPA was formulated as conjugated Pfs25M in 4 mM PBS to a 2X dilution of the high dose (188 (Micro)g/ml in 0.5 ml volume) in cGMP compliance at Walter Reed Bio-production facility in April 2016 and will be provided as a single use vial.
BiologicalPfs230D1M-EPA
The Pfs230D1M-EPA was formulated as conjugated Pfs230D1M in 4 mM PBS to a 2X dilution of the high dose (160 (Micro)g/ml in 0.5 ml volume) in cGMP compliance at Walter Reed Bio-production facility in April 2016 and will be provided as a single use vial.
OtherAS01
AS01B adjuvant will also be provided as a single use vial by GSK, 100 microgram/mL MPL and 100microgram/mL QS21 in a liposomal formulation in a volume of 0.625 mL. One dose injected of AS01B corresponds to 50 μg QS21 and 50 μg MPL.
BiologicalEngerix-B
ENGERIX-B (hepatitis B vaccine; recombinant): is a sterile suspension of noninfectious hepatitis B virus surface antigen (HBsAg) for intramuscular administration. It contains purified HBsAg obtained by culturing genetically engineered Saccharomyces cerevisiae cells, which carry the surface antigen gene of the hepatitis B virus. Each 1-mL adult dose contains 20 g of HBsAg adsorbed on 0.5 mg aluminum as aluminum hydroxide. FDA approved for persons 20 years of age and older for a series of 3 doses on a 0-, 1-, 6-month schedule.
BiologicalMenactra
Menactra is FDA approved for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135 (but does not protect against serotype B) for use in individuals 9 months through 55 years of age
OtherNormal Saline
Sterile isotonic (0.9%) normal saline will be commercially procured in the US and shipped to Mali at ambient temperature. Normal saline will be administered in a 0.5 mL dose as an intramuscular injection. Normal saline will also be used for diluting Pfs25M-EPA and Pfs230D1M-EPA prior to formulation with AS01B for the lower dose groups in Bamako, Mali.
DrugCoartem
Artemether/lumefantrine (Coartem(R)) is a licensed antimalarial in the US and Mali for treatment of uncomplicated malaria. It has an excellent safety profile and is widely used to treat malaria. Subjects who may have any contraindications to the use of these drugs will be excluded at screening. Coartem will be dosed with food and administered over 3 days for a total of 6 doses, as per package insert and standard adult dosing

What researchers measure

Primary outcomes

Number of Participants With Local and Systemic Adverse Events in Year 1
Number of participants with local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine
Time frame: Within 7 days after each vaccination
Number of Participants With Local and Systemic Adverse Events in Year 2
Number of participants with local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine
Time frame: Within 7 days after each vaccination

Results

Posted Jan 28, 2022

Limitations and caveats

No limitations or caveats to report.

Participant flow

Community permission was obtained from village elders and other community members in Sotuba/Bamako, Bancoumana, and Doneguebougou after explanation and discussion of the study at a community meeting. A general announcement inviting household and family members to the participating clinic to learn about the study was made at the time of community permission, using local radio or any traditional channel of communication.

Year 1

Participant flow — Year 1
Milestone	Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days
Started	5	10	5	10	56	61	5	10	10	10	119
Completed	5	8	5	9	49	51	5	9	10	10	104
Not completed	0	2	0	1	7	10	0	1	0	0	15
Withdrew: Withdrawal by subject	0	0	0	0	1	3	0	1	0	0	3
Withdrew: Travel	0	1	0	0	4	5	0	0	0	0	8
Withdrew: Joined army	0	1	0	0	0	0	0	0	0	0	0
Withdrew: Subject met withdrawal criteria	0	0	0	1	0	0	0	0	0	0	0
Withdrew: Lost to follow-up	0	0	0	0	1	0	0	0	0	0	2
Withdrew: Protocol violation	0	0	0	0	1	1	0	0	0	0	2
Withdrew: Pregnancy	0	0	0	0	0	1	0	0	0	0	0

Year 2

Participant flow — Year 2
Milestone	Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days
Started	5	8	5	9	49	51	5	9	10	10	104
Completed	5	7	4	8	36	40	4	8	10	9	79
Not completed	0	1	1	1	13	11	1	1	0	1	25
Withdrew: Lost to follow-up	0	0	0	0	2	1	0	0	0	0	0
Withdrew: Did not rescreen	0	0	1	1	9	6	0	1	0	0	21
Withdrew: Met withdrawal criteria	0	0	0	0	1	2	0	0	0	0	1
Withdrew: Travel	0	1	0	0	0	1	0	0	0	1	3
Withdrew: Non-compliant	0	0	0	0	1	1	0	0	0	0	0
Withdrew: Withdrawal by subject	0	0	0	0	0	0	1	0	0	0	0

Outcome measures

PrimaryNumber of Participants With Local and Systemic Adverse Events in Year 1

Number of participants with local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine

Time frame:: Within 7 days after each vaccination
Reported as:: Count of participants · Participants

Number of Participants With Local and Systemic Adverse Events in Year 1
Participants	Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days
Number of Participants With Local and Systemic Adverse Events in Year 1	2	6	4	6	31	25	3	8	2	3	52

PrimaryNumber of Participants With Local and Systemic Adverse Events in Year 2

Number of participants with local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine

Time frame:: Within 7 days after each vaccination
Reported as:: Count of participants · Participants

Number of Participants With Local and Systemic Adverse Events in Year 2
Participants	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days
Number of Participants With Local and Systemic Adverse Events in Year 2	28	27	20

Adverse events

Collected over Adverse Events were assessed 7 days from the time of each vaccination in Years 1 and 2. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	0/5 (0%)	0/5 (0%)	2/5 (40%)
Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	0/10 (0%)	0/10 (0%)	7/10 (70%)
Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	0/5 (0%)	0/5 (0%)	5/5 (100%)
Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	0/10 (0%)	0/10 (0%)	8/10 (80%)
Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	0/56 (0%)	0/56 (0%)	53/56 (94.6%)
Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	0/61 (0%)	0/61 (0%)	58/61 (95.1%)
Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	0/5 (0%)	0/5 (0%)	4/5 (80%)
Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	0/10 (0%)	0/10 (0%)	9/10 (90%)
Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	0/10 (0%)	0/10 (0%)	4/10 (40%)
Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	0/10 (0%)	1/10 (10%)	4/10 (40%)
Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days	0/119 (0%)	1/119 (0.8%)	79/119 (66.4%)

Most frequent serious events

Most frequent serious events
Event	Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days
Pulmonary TuberculosisInfections and infestations	—	—	—	—	—	—	—	—	—	1/10	0/119
Snake BiteInjury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	0/10	1/119

Most frequent other events

Showing 10 of 57

Most frequent other events
Event	Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days
Injection site painGeneral disorders	2/5	7/10	4/5	7/10	51/56	48/61	4/5	8/10	0/10	3/10	38/119
HeadacheNervous system disorders	0/5	0/10	1/5	4/10	23/56	25/61	1/5	5/10	1/10	1/10	11/119
NeutropeniaBlood and lymphatic system disorders	1/5	2/10	0/5	3/10	7/56	3/61	0/5	0/10	1/10	0/10	7/119
Alanine aminotransferase increasedInvestigations	0/5	0/10	1/5	0/10	3/56	1/61	0/5	1/10	0/10	0/10	2/119
ArthralgiaMusculoskeletal and connective tissue disorders	0/5	0/10	0/5	2/10	7/56	2/61	0/5	2/10	0/10	1/10	1/119
Blood creatinine increasedInvestigations	0/5	0/10	1/5	0/10	0/56	1/61	0/5	0/10	0/10	0/10	3/119
FatigueGeneral disorders	1/5	0/10	0/5	1/10	3/56	1/61	1/5	1/10	0/10	0/10	1/119
Gastrointestinal disorderGastrointestinal disorders	0/5	0/10	0/5	0/10	0/56	0/61	1/5	0/10	0/10	0/10	0/119
Injection site movement impairmentGeneral disorders	0/5	0/10	0/5	2/10	6/56	2/61	0/5	2/10	0/10	0/10	3/119
MyalgiaMusculoskeletal and connective tissue disorders	0/5	0/10	0/5	0/10	4/56	1/61	1/5	0/10	0/10	0/10	1/119

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days	Total
<=18 years	0	0	0	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	5	10	5	10	56	61	5	10	10	10	119	301
>=65 years	0	0	0	0	0	0	0	0	0	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days	Total
Female	1	2	2	3	18	17	1	4	1	6	41	96
Male	4	8	3	7	38	44	4	6	9	4	78	205

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days	Total
Bambara	2	5	0	7	14	19	3	5	5	4	27	91
Bozo	0	0	0	0	0	1	0	0	0	0	2	3
Malinke	0	1	2	0	25	24	0	0	2	1	56	111
Peulh	0	0	2	1	6	5	1	0	1	1	5	22
Sarakole	0	1	0	1	11	11	0	3	0	3	25	55
Sonrhai	0	0	0	0	0	1	0	0	0	0	1	2
Other	3	3	1	1	0	0	1	2	2	1	3	17

Region of Enrollment
Region of Enrollment(participants)	Pilot/Safety Arm 1a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 1b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 2b: Dosing Interval 0, 28, 168 Days	Safety/Efficacy Arm 2c: Dosing Interval 0, 28, 168, 476 Days	Safety/Efficacy Arm 2d: Dosing Interval 0, 28, 168, 476 Days	Pilot/Safety Arm 3a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Arm 3b: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4a: Dosing Interval 0, 28, 168 Days	Pilot/Safety Comparator Arm 4b: Dosing Interval 0, 28, 168 Days	Safety Comparator & Efficacy Comparator Arm 4c: Dosing Interval 0, 28, 168, 476 Days	Total
Mali	5	10	5	10	56	61	5	10	10	10	119	301

Study locations

1 site

Bancoumana Malaria Vaccine Center
Bamako, Mali

References and documents

Publications

Wu Y, Przysiecki C, Flanagan E, Bello-Irizarry SN, Ionescu R, Muratova O, Dobrescu G, Lambert L, Keister D, Rippeon Y, Long CA, Shi L, Caulfield M, Shaw A, Saul A, Shiver J, Miller LH. Sustained high-titer antibody responses induced by conjugating a malarial vaccine candidate to outer-membrane protein complex. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18243-8. doi: 10.1073/pnas.0608545103. Epub 2006 Nov 16. PubMed 17110440 ↗
Tachibana M, Wu Y, Iriko H, Muratova O, MacDonald NJ, Sattabongkot J, Takeo S, Otsuki H, Torii M, Tsuboi T. N-terminal prodomain of Pfs230 synthesized using a cell-free system is sufficient to induce complement-dependent malaria transmission-blocking activity. Clin Vaccine Immunol. 2011 Aug;18(8):1343-50. doi: 10.1128/CVI.05104-11. Epub 2011 Jun 29. PubMed 21715579 ↗
Diallo M, Toure AM, Traore SF, Niare O, Kassambara L, Konare A, Coulibaly M, Bagayogo M, Beier JC, Sakai RK, Toure YT, Doumbo OK. Evaluation and optimization of membrane feeding compared to direct feeding as an assay for infectivity. Malar J. 2008 Dec 2;7:248. doi: 10.1186/1475-2875-7-248. PubMed 19055715 ↗
Healy SA, Sagara I, Assadou MH, Katile A, Kone M, Imeru A, Kwan JL, Swihart BJ, Fintzi J, Potter GE, Zeguime A, Dolo A, Diarra B, Narum DL, Rausch KM, MacDonald NJ, Zhu D, Mohan R, Thera I, Morrison RD, Zaidi I, Doritchamou JYA, Sylla D, Hume JCC, Coulibaly MB, Morelle D, Lievens M, Doumbo OK, Duffy PE; Pfs230D1 Vaccine Team. A Vaccine to Block Plasmodium falciparum Transmission. NEJM Evid. 2025 Jul;4(7):EVIDoa2400188. doi: 10.1056/EVIDoa2400188. Epub 2025 Jun 24. PubMed 40552966 ↗
Cao Y, da Silva Araujo M, Lorang CG, Dos Santos NAC, Tripathi A, Vinetz J, Kumar N. Distinct immunogenicity outcomes of DNA vaccines encoding malaria transmission-blocking vaccine target antigens Pfs230D1M and Pvs230D1. Vaccine. 2025 Feb 15;47:126696. doi: 10.1016/j.vaccine.2024.126696. Epub 2025 Jan 8. PubMed 39787798 ↗

Study documents

Protocol and statistical analysis plan · Jul 21, 2020

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 10, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02942277
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party: Sponsor
First posted: Oct 24, 2016
Start date: Oct 21, 2016
Primary completion: Jul 15, 2020
Completion: Jul 15, 2020
Results posted: Jan 28, 2022
Last update: Dec 10, 2024

Study contacts

Patrick E Duffy, M.D.

principal investigator · National Institute of Allergy and Infectious Diseases (NIAID)

Oversight

FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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