About the Trials
Phase 1 MLSPZV3 Trial:
- Trial Name: 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
- Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
- Completion Date: February 13, 2020
Phase 2 MLSPZV4 Trial:
- Trial Name: Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Malaria Transmission Season in Healthy African Adult Women of Childbearing Potential in Mali
- ClinicalTrials.gov ID: NCT03989102
- Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
- Completion Date: March 17, 2023
According to recent research published in The Lancet Infectious Diseases, an experimental malaria vaccine, PfSPZ (Sanaria), was found to be safe and well tolerated in adults and women in Mali who anticipated conception. The radiation-attenuated, non-replicating, whole-organism vaccine based on the Plasmodium falciparum sporozoites has previously shown efficacy in protecting African adult patients from infection.1,2
During pregnancy, P falciparum parasitemia can cause maternal, fetal, and infant mortality. Additionally, poor pregnancy outcomes are related to blood-stage parasite sequestration. The investigators aimed to explore the vaccine’s safety and efficacy in adults and women who anticipated becoming pregnant by conducting 2 randomized, double-blind, placebo-controlled clinical trials, the phase 1 trial MLSPZV3 (NCT03510481) and phase 2 trial MLSPZV4 (NCT03989102).2
For the phase 1 MLSPZV3 trial, adults aged 18 to 35 years were enrolled and stratified by village. All 478 patients were randomly assigned using block randomization to receive either 3 doses of the 9 × 105 PfSPZ vaccine or saline placebo which were administered in a 4-week (weeks 0, 1, and 4) or 16-week schedule (weeks 0, 8, and 16). Additionally, patients received a booster dose about 1 year later.2,3
Similarly, the phase 2 MLSPZV4 trial enrolled non-pregnant women aged 18 to 38 years who anticipated being pregnant within a year of trial enrollment. Two weeks prior to dose 1, all women received presumptive artemether–lumefantrine (20mg/120mg) 2 times per day for 3 days. Following this, they were randomly assigned using block randomization to receive either 3 doses of either 9 × 105 or 1.8 × 106 PfSPZ vaccine, or a saline placebo. Regardless of the vaccine they received or their dosage, all women adhered to a 4-week vaccination schedule (weeks 0, 1, and 4).2,4
The investigators note that across both trials, all participants received artemether–lumefantrine 2 weeks before dose 3, and in the MLSPZV3 trial, an additional dose at 2 weeks before the booster (dose 4). Both trials’ outcomes were the number of participants with adverse events (AEs) after each vaccination within year 1. This was assessed 7 days after each vaccination, which occurred at days 1, 8, and 29. Additionally, the secondary outcome assessed vaccine efficacy from dose 3 until the end of transmission season in the modified intention-to-treat population.3,4
Further, in exploratory analyses, MLSPZV4 evaluated the incidence of maternal obstetric and neonatal outcomes as safety outcomes, and vaccine efficacy against P falciparum parasitemia during pregnancy, which was defined as time-to-first positive blood smear after conception. In addition, women in the MLSPZV4 trial were followed at least once per month with human chorionic gonadotropin testing, and those who became pregnant received standard of care—intermittent presumptive sulfadoxine–pyrimethamine antimalarial drugs after the first trimester—during routine antenatal visits.2,4
According to the phase 1 MLSPZV3 trial findings, the majority of patients in each group (4-week group: 68 of 70 patients, 97%; 16-week group: 66 of 69, 96%; and placebo group: 70 of 71, 99%) received all 3 doses during year 1. In the 4-week and 16-week groups, the vaccine did not show efficacy against parasitemia at years 1 (4-week: 27% [95% CI –18 to 55]; and 16-week: 16% [–34 to 48]) and 2 (4-week: 42% [–5 to 68]; and 16-week: –14% [–95 to 33]), with efficacies being similar or worse against clinical malaria compared with saline.1,2
In the phase 2 MLSPZV4 trial, 407 women were assessed for eligibility, and 300 women were randomly assigned, with 100 participants per group (PfSPZ Vaccine, 9 × 105, 1·8 × 106, or saline). According to the findings, both doses of the PfSPZ vaccine showed significant efficacy against parasitemia at years 1 (9 × 105 dose: 41% [15 to 59], p = .0069; and 1.8 × 106 dose: 54% [34 to 69], p < .0001) and 2 (9 × 105 dose: 61% [36 to 77], p = .0011; and 1.8 × 106 dose: 45% [13 to 65], p = .029). Efficacy was also observed against clinical malaria for both doses at years 1 (9 × 105 dose: 47% [20 to 65], p = .0045; and 1.8 × 106 dose: 48% [22 to 65], p = .0013) and 2 (9 × 105 dose: 56% [22 to 75], p = .0081; and 1.8 × 106 dose: 40% [2 to 64], p = .069). Further, vaccine efficacy against post-conception P falciparum parasitemia during first pregnancies that arose during the 2-year follow-up was approximately 57% (14 to 78; p = .017) in the 9 × 105 group compared with 49% (3 to 73; p = .042) in the 1.8 × 106 group. Among the 55 women who were pregnant within 24 weeks after receiving their third dose, vaccine efficacy was approximately 65% (23 to 84; p = .0088) with the 9 × 105 group and 86% (64 to 94; p < .0001) for the 1.8 × 106 group.1,2
Additionally, first trimester miscarriages were the most commonly reported serious AE but occurred at a similar rate across study groups. There was 1 unrelated maternal death that occurred 425 days after the last vaccine dose in the 1.8 × 106 group as a result of peritonitis shortly after childbirth.2
The most related AEs events reported in MLSPZV3 and MLSPZV4 were mild, and the frequency of AEs in the PfSPZ vaccine groups did not differ from that in the placebo group. There were 2 unrelated serious AEs that occurred in the MLSPZV3 trial: 1 participant had appendicitis in the 9 × 105 group, and the other was a participant in the placebo group whose death was related to a car accident.2
“Preconception immunization is a new strategy to reduce mortality for women with malaria in pregnancy. Existing measures are not protecting women from malaria in pregnancy. A safe and effective vaccine is urgently needed, and our results indicate PfSPZ Vaccine might be a suitable candidate,” said the researchers in a news release.1
REFERENCES
1. NIH/National Institute of Allergy and Infectious Diseases. Candidate malaria vaccine provides lasting protection in NIH-sponsored trials. News release. August 14, 2024. Accessed September 16, 2024. https://www.eurekalert.org/news-releases/1054618
2. Diawara, H, Healy, SA, Mwakingwe-Omari, A, et al.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. doi:10.1016/S1473-3099(24)00360-8
3. 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 identifier: NCT03510481. Updated August 20, 2021. Accessed September 17, 2024. https://clinicaltrials.gov/study/NCT03510481
4. Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Malaria Transmission Season in Healthy African Adult Women of Childbearing Potential in Mali.ClinicalTrials.gov identifier: NCT03989102. Updated March 19, 2024. Accessed September 17, 2024. https://clinicaltrials.gov/study/NCT03989102
