Malaria
Conditions
Keywords
Pregnancy, Tolerability, Immune, Response, Vaccination
Brief summary
Background: Malaria is a disease spread by mosquitos. Pregnant women are highly susceptible to malaria. This can lead to poor health outcomes for pregnant women and their babies. Researchers want to test a malaria vaccine in women of child bearing potential (WOCBP) and pregnant women. This has not been done before. Objective: To assess the safety and tolerability of PfSPZ vaccine in healthy Malian WOCBP. Eligibility: Healthy women ages 18 38 who live in Ouelessebougou, Mali, and surrounding villages Design: Participants will be screened with: * Physical exam * Medical history * Blood, urine, and heart tests * Multiple-choice test about malaria Participants will get 3 injections by needle into a vein of the study vaccine or a placebo. All 3 will be within 1 month. They will not know whether they receive the vaccine or placebo. Participants will receive treatment to prevent malaria. This will be about 2 weeks before the first and third injections. After the third injection, participants will be followed for about 1 year. They will be tested to see if the vaccine is safe and protects against malaria infection. They will have blood tests. If participants get a rash or injection site reaction, photos of the site may be taken. Any women who become pregnant during the trial will be followed through the end of pregnancy. Babies and their mothers will be followed through the first year of life
Detailed description
Pregnant women are highly susceptible to Plasmodium falciparum malaria, leading to substantial maternal, perinatal, and infant mortality. While malaria vaccine development has made significant progress in recent years, no trials of malaria vaccines have ever been conducted in only women of child bearing potential (WOCBP) or in pregnant women. PfSPZ Vaccine (Sanaria, Inc) is an advanced malaria candidate being developed for use in pregnant women, owing in part to its highly favorable safety profile. The vaccine is comprised of aseptic, metabolically active, non-replicating, purified, cryopreserved P. falciparum sporozoites. In multiple double-blind, placebo-controlled trials, there have been no differences in adverse events between vaccinees versus controls. PfSPZ Vaccine induces immune responses to the sporozoite and liver stages of parasite development in the human host and prevents progression to blood stage parasitemia as well as averting disease sequelae; a compelling rationale to test PfSPZ Vaccine for its benefits in this proposed population. Sanaria has already achieved vaccine efficacy against homologous and heterogenous parasite populations in endemic areas following three doses of PfSPZ Vaccine in several studies with 9.0x10\^5 and 1.8x10\^6 PfSPZ Vaccine and has explored accelerated regimens, such as 1, 8, 29 days. Accelerated PfSPZ Vaccine regimens such as this could induce protection earlier in pregnancy, minimizing the period at risk and improving pregnancy outcomes over the control group. Given this, the Malaria Research and Training Center, the Laboratory of Malaria Immunology and Vaccinology National Institute of Allergy and Infectious Diseases, and Sanaria, Inc. propose to initiate testing of the day 1, 8, and 29 dosing regimen of PfSPZ Vaccine in WOCBP, and in subsequent studies, in pregnant women, using doses of 9.0x10\^5 and 1.8x10\^6 PfSPZ Vaccine. This will be the first step in a clinical development plan for PfSPZ Vaccine in WOCBP and pregnant women: 1) safety and efficacy studies in non-pregnant WOCBP (this trial), 2) studies of the safety and efficacy of a primary immunization series in all trimesters, and 3) studies to evaluate the safety and efficacy of boosting during pregnancy. A pregnancy registry study (#17-I-N018) has been ongoing in Mali since 2017 to gain background data on maternal/fetal outcomes in the target population in anticipation of this study. Women who become pregnant during the course of this study, and their offspring, will be followed for maternal clinical outcomes and malaria infection.
Interventions
BIOLOGICALPfSPZ Vaccine
PfSPZ vaccine is comprised of aseptic, metabolically active, non-replicating, purified, cryopreserved P. falciparum sporozoites.
OTHERNormal Saline
Sterile isotonic (0.9%) normal saline is a clear liquid, making it indistinguishable from the study product when drawn up into a syringe; and will be used as a placebo, rather than a comparator vaccine
Sponsors
Malaria Research and Training Center, Bamako, Mali
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 38 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: 1. Females of child bearing potential aged greater than or equal to 18 and less than or equal to 38 years 2. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process 3. In good general health and without clinically significant medical history 4. Willing to have blood samples stored for future research 5. Available for the duration of the study 6. Must be willing to use reliable contraception (defined as: pharmacologic contraceptives \[parental delivery\] or pre-existing intrauterine or implantable device) from 21 days prior to study day 1 to 28 days after last vaccination 7. Report being interested in becoming pregnant within the next 1-2 years
Exclusion criteria
1. Pregnancy at the time of enrollment/vaccination, as determined by a positive urine or serum human chorionic gonadotropin (beta-hCG) test 2. Biologically unable to become pregnant secondary to: surgical sterilization, premature ovarian insufficiency (defined as no menses for greater than or equal to 12 months without an alternative medical cause) 3. 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 4. Hemoglobin (Hgb), white blood cell count (WBC), absolute neutrophils, and platelets outside the local laboratory-defined limits of normal and greater than or equal to Grade 2 (subjects may be included at the investigators discretion for not clinically significant abnormal values) 5. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal and greater than or equal to Grade 2 (subjects may be included at the investigators discretion for not clinically significant abnormal values) 6. Infected with human immunodeficiency virus (HIV) 7. Known or documented sickle cell disease by history (Note: known sickle cell trait is NOT exclusionary) 8. Clinically significant abnormal electrocardiogram (ECG) such as abnormal corrected QT interval (QTc). 9. 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 10. History of receiving any investigational product within the past 30 days 11. 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 12. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months 13. History of a severe allergic reaction (Grade 2 or higher or per PI discretion) or anaphylaxis 14. 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) 15. 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 16. Known immunodeficiency syndrome 17. Known asplenia or functional asplenia 18. Use of chronic (greater than or equal to 14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone greater than or equal to 20 mg/day) or immunosuppressive drugs within 30 days of vaccination 19. 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 20. Receipt of immunoglobulins and/or blood products within the past six months 21. Previous receipt of an investigational malaria vaccine in the last five years 22. Known allergies or other contraindications against use of artemeter/lumefantrine 23. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events Within 7 Days After Each Vaccine Administration | 7 days after each vaccination at days 1, 8, and 29 | Assess safety and tolerability of PfSPZ Vaccine primary series in healthy Malian women of child-bearing potential (WOCBP) when given at 1, 8, 29 days at two doses (9 x10\^5; 1.8 x10\^6). |
Countries
Mali
Participant flow
Pre-assignment details
324 participants were enrolled, but 24 participants were not assigned to any treatment arms due to withdrawn consent; thus 300 total participants were assigned to treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Participants received 3 doses of PfSPZ Vaccine (9 x10\^5) via direct venous inoculation (DVI) at 1, 8, 29 days. Oral antimalarial treatment with artemether/lumefantrine (AL) was given 2 weeks prior to 1st and 3rd injection. | 100 |
| Arm 2 Participants received 3 doses of PfSPZ Vaccine (1.8 x10\^6) via direct venous inoculation (DVI) at 1, 8, 29 days. Oral antimalarial treatment with artemether/lumefantrine (AL) was given 2 weeks prior to 1st and 3rd injection. | 100 |
| Arm 3 Participants received 3 doses of saline injection via direct venous inoculation (DVI) at 1, 8, 29 days. Oral antimalarial treatment with artemether/lumefantrine (AL) was given 2 weeks prior to 1st and 3rd injection. | 100 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Post-Year 3 (up to 3 Years, 8 Months) | Lost to Follow-up | 1 | 2 | 2 |
| Post-Year 3 (up to 3 Years, 8 Months) | Missed last study visit | 2 | 1 | 0 |
| Post-Year 3 (up to 3 Years, 8 Months) | Relocated | 0 | 0 | 1 |
| Post-Year 3 (up to 3 Years, 8 Months) | Travel | 0 | 3 | 0 |
| Post-Year 3 (up to 3 Years, 8 Months) | Widowhood | 1 | 0 | 0 |
| Post-Year 3 (up to 3 Years, 8 Months) | Withdrawal by Subject | 1 | 1 | 1 |
| Year 1 | Lost to Follow-up | 5 | 2 | 5 |
| Year 1 | Subject met withdrawal criteria | 1 | 0 | 1 |
| Year 1 | Withdrawal by Subject | 6 | 2 | 7 |
| Year 2 | Death | 0 | 1 | 0 |
| Year 2 | Definitive displacement outside the study site | 0 | 1 | 0 |
| Year 2 | Lost to Follow-up | 7 | 3 | 4 |
| Year 2 | P11 missing | 1 | 3 | 7 |
| Year 2 | P16 missing | 4 | 2 | 1 |
| Year 2 | Subject missed last study visit | 0 | 1 | 0 |
| Year 2 | Subject non-compliant | 3 | 2 | 0 |
| Year 2 | Subject not reachable | 0 | 0 | 1 |
| Year 2 | Travel | 1 | 0 | 1 |
| Year 2 | Withdrawal by Subject | 3 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Arm 2 | Arm 1 | Arm 3 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 300 Participants | 100 Participants | 100 Participants | 100 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — |
| Race/Ethnicity, Customized Bambara | 222 Participants | 76 Participants | 72 Participants | 74 Participants |
| Race/Ethnicity, Customized Bobo | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Dogon | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Gana | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Kakolo | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Koroko | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Malinke | 11 Participants | 4 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Mianka | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Mossi | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Peulh | 24 Participants | 7 Participants | 7 Participants | 10 Participants |
| Race/Ethnicity, Customized Sarakole | 17 Participants | 5 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized Senoufo | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Soninke | 10 Participants | 1 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Sonrhai | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Wolof | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Mali | 300 Participants | 100 Participants | 100 Participants | 100 Participants |
| Sex: Female, Male Female | 300 Participants | 100 Participants | 100 Participants | 100 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 1 / 100 | 0 / 100 |
| other Total, other adverse events | 51 / 100 | 43 / 100 | 43 / 100 |
| serious Total, serious adverse events | 0 / 100 | 0 / 100 | 0 / 100 |
Outcome results
Primary
Number of Participants With Adverse Events Within 7 Days After Each Vaccine Administration
Assess safety and tolerability of PfSPZ Vaccine primary series in healthy Malian women of child-bearing potential (WOCBP) when given at 1, 8, 29 days at two doses (9 x10\^5; 1.8 x10\^6).
Time frame: 7 days after each vaccination at days 1, 8, and 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 | Number of Participants With Adverse Events Within 7 Days After Each Vaccine Administration | 51 Participants |
| Arm 2 | Number of Participants With Adverse Events Within 7 Days After Each Vaccine Administration | 43 Participants |
| Arm 3 | Number of Participants With Adverse Events Within 7 Days After Each Vaccine Administration | 43 Participants |