Safety Evaluation of PfSPZ Vaccine in Pregnant Women in Mali (MalVIP1)

Malaria Clinical Trial

Official title: Phase 1 Safety Evaluation of PfSPZ Vaccine in Pregnant Women in Mali (MalVIP1)

Status Suspended

Clinical Trial Summary

Background:

Malaria is a disease that affects many people in Africa. It is caused by germs carried by some mosquitoes. A person bitten by an infected mosquito will get malaria. Most malaria infections cause only mild symptoms or none at all, but sometimes the disease can be deadly. Malaria can also harm pregnant women. They may lose their pregnancies or deliver too early, and the mother and newborn may die. An experimental malaria vaccine (PfSPZ) has shown some protection against malaria infection. It is not yet known if PfSPZ is safe for pregnant women.

Objective:

To test the PfSPZ vaccine in pregnant women.

Eligibility:

Healthy women aged 18 to 34 years at 14 to 32 weeks gestation with 1 fetus.

Design:

The study will be in Mali. Participants will have about 40 clinic visits over 20 months.

They will be screened. They will have an ultrasound exam and a test of their heart function. They will have blood and urine tests.

Participants will receive an injection through a needle into a vein on 3 visits over 1 month. Some will receive the PfSPZ vaccine; others will be injected with salt water. They will not know which injection they are getting.

After the last injection, participants will visit the clinic every 2 weeks. They will have blood tests at each visit.

After giving birth, participants and their infants will visit the clinic every 2 weeks for 4 months; then they will have visits each month until the infant is 1 year old. The infant will be examined and will have blood tests at each visit.

Clinical Trial Description

Study Description:

A randomized double blind, placebo-controlled study to assess the safety, tolerability, immunogenicity and protective efficacy of a 1, 8, 29-day regimen of 9x105 PfSPZ of PfSPZ Vaccine or placebo (normal saline) in healthy pregnant women and their fetus/newborn. The first immunization is to be administered at 16 0/7 to 32 6/7 weeks of gestation and targeted to be completed prior to delivery. Offspring and post-partum women will be followed for 12 months post-delivery.

The study is composed of two cohorts (3rd trimester: Arms 1A, 2A, 2nd trimester: Arms 1B, 2B) with two arms (PfSPZ Vaccine, normal saline placebo) and associated offspring. Enrollment and vaccinations will be staggered for safety with only third trimester women (n=30; based on guidance provided by regulatory bodies) enrolling first in two separate subsets (n=10 [5 PfSPZ Vaccine/5 normal saline], n=20 [10 PfSPZ Vaccine/10 normal saline]) and receiving all three doses of vaccine in a staggered manner and undergoing safety reviews prior to further enrollments. Third trimester enrollment in this staggered manner is to account for any significant events occurring immediately post initial vaccinations with the smaller first subset of women (n=10; DSMB review). After all third trimester pregnancy outcomes are reviewed (by DSMB, FDA, Sponsor, EC/IRB), an additional cohort of women in their second trimester will be vaccinated in two separate subsets (n=10 [5 PfSPZ Vaccine/5 normal saline], n=20 [10 PfSPZ Vaccine/10 normal saline]) separated by at least six weeks. A longer time period of review will be conducted during the 2nd trimester out of additional safety measures to ensure no significant events of concern occur post receipt of a full vaccination series (n=10; DSMB review) before proceeding to the last subset of women (n=20).

Arm 1 (9x10^5 PfSPZ Vaccine): (n = 30) pregnant women will receive three doses of PfSPZ Vaccine (9x10^5 PfSPZ) via direct venous inoculation (DVI) at 1, 8, 29 days

• Arm 1A: (n=15) women 28 0/7 to 32 6/7 WGA (third trimester) at time of first vaccination

• Arm 1B: (n=15) women 16 0/7 to 27 6/7 WGA (second trimester) at time of first vaccination

Arm 2 (normal saline): (n = 30) pregnant women will receive normal saline via DVI at 1, 8, 29 days

• Arm 2A: (n=15) women 28 0/7 to 32 6/7 WGA (third trimester) at time of first vaccination

• Arm 2B: (n=15) women 16 0/7 to 27 6/7 WGA (second trimester) at time of first vaccination

All participants will receive intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) as per standard of care in Mali. The study team will coordinate with the women s antenatal care (ANC) provider to time her IPTp prior to vaccine dose 1 (approximately 2 weeks prior) and between vaccine dose 2 and dose 3 (approximately 2 weeks prior to dose 3) within the protocol defined windows.

Pregnant women will be monitored closely for the duration of their pregnancy and for at least 12 months post-partum for safety, tolerability, immunogenicity, and malaria infection during the follow-up period.

Infants (n=up to 60) born to enrolled women will also be monitored closely for 12 months post-delivery for safety, immunogenicity, and malaria infection.

Objectives:

Primary Objectives:

-To describe the safety of PfSPZ Vaccine at 9x10^5 PfSPZ at dosing schedule of 1, 8, 29 days in pregnant women and their fetuses using a composite measure of adverse maternal and birth outcomes

Secondary Objectives:

• To describe the safety and tolerability of PfSPZ Vaccine at 9x10^5 PfSPZ at dosing schedule of 1, 8, 29 days in pregnant women and their fetuses using solicited adverse events (AEs), unsolicited AEs, and laboratory abnormalities

• To describe the safety of maternal vaccination with PfSPZ Vaccine in infants

Exploratory Objectives:

• To explore the protective efficacy against Pf malaria of PfSPZ Vaccine in pregnant women (peripheral blood, placenta) and infants (peripheral, cord blood)

• To assess the immune response to PfSPZ Vaccine in pregnant women and infants and their association with protection against Pf malaria

• To assess genetic relatedness of the PfSPZ Vaccine parasite strain to malaria infection parasites in pregnant women and infants

Endpoints:

Primary Endpoints:

-Composite endpoint of adverse maternal or birth outcomes defined as: preterm birth, miscarriage, stillbirth, early neonatal death, direct maternal death, low birth weight, small for gestational age (counts and proportions)

Secondary Endpoints:

• Safety and tolerability in pregnant women and their fetuses

• Solicited local and systemic AEs through 7 days post injection (counts and proportions)

• Clinical laboratory parameters through 14 days post injection (counts and proportions)

• All unsolicited AEs, AEs of special interest (AESIs), and serious AEs (SAEs) through delivery and six months thereafter (counts and proportions)

• Safety in infants

• Neonatal SAEs (including late neonatal deaths or AESIs) through 6 months of age (counts and proportions)

• Growth and developmental milestones through 1 year of age (counts and proportions)

• All unsolicited AEs through 6 months of age (counts and proportions)

Exploratory Endpoints:

• Protective efficacy

• Pf blood stage infection measured by blood smear and nucleic acid detection in women starting immediately following 3rd injection over 24-week period (time to event, binary)

• Pf blood stage infection measured by blood smear and nucleic acid detection in infants through 1 year of age (time to event, binary)

• Pf blood stage infection measure by blood smear and nucleic acid detection in post-partum women starting immediately following 3rd injection until 1 year post-delivery (time to event, binary)

• Pf infection measure by blood smear and nucleic acid in cord blood (counts and proportions)

• Pf infection measure by blood smear and nucleic acid in placentas (counts and proportions)

• Immune responses (antibody, cellular) to PfSPZ Vaccine in pregnant and post-partum women and infants and their association with protection against Pf malaria

• Genotyping of maternal peripheral blood or placental and newborn/infant peripheral or cord blood Pf parasites ;

Related Conditions & MeSH terms

• Malaria

• NCT number: NCT05652504
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Suspended
• Phase: Phase 1
• Start date: June 26, 2024
• Completion date: November 30, 2024