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

NCT03989102 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 99991911319-I-N113
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 1

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

Conditions

Malaria

Keywords

Pregnancy; Tolerability; Immune; Response; Vaccination

Outcome Measures

Primary Outcomes (1)

• 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).

  7 days after each vaccination at days 1, 8, and 29

Study Arms (3)

Arm 1

EXPERIMENTAL

Arm 1: (n= 100) will receive 3 doses of PfSPZ Vaccine (9 x10(5)) via direct venous inoculation (DVI) at 1, 8, 29 days.

Biological: PfSPZ Vaccine

Arm 2

EXPERIMENTAL

Arm 2: (n= 100) will receive 3 doses of PfSPZ Vaccine (1.8 x10(6)) via DVI at 1, 8, 29 days.

Biological: PfSPZ Vaccine

Arm 3

PLACEBO COMPARATOR

Arm 3: (n=100): will receive 3 doses of normal saline (placebo) injection via DVI at 1, 8, 29 days.

Other: Normal Saline

Interventions

PfSPZ Vaccine BIOLOGICAL

PfSPZ vaccine is comprised of aseptic, metabolically active, non-replicating, purified, cryopreserved P. falciparum sporozoites.

Arm 1; Arm 2

Normal Saline OTHER

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

Arm 3

Eligibility Criteria

• Age: Up to 38 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Females of child bearing potential aged greater than or equal to 18 and less than or equal to 38 years
• 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
• Willing to have blood samples stored for future research
• Available for the duration of the study
• 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
• Report being interested in becoming pregnant within the next 1-2 years

You may not qualify if:

• Pregnancy at the time of enrollment/vaccination, as determined by a positive urine or serum human chorionic gonadotropin (beta-hCG) test
• 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)
• 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 (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)
• 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)
• Infected with human immunodeficiency virus (HIV)
• Clinically significant abnormal electrocardiogram (ECG) such as abnormal corrected QT interval (QTc).
• 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
• 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 (Grade 2 or higher or per PI discretion) or anaphylaxis
• 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)
• 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
• Known immunodeficiency syndrome

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Malaria Research and Training Center, Bamako, Mali: collaborator

Study Sites (1)

Ouelessebougou Health Research Unit

Wolossébougou, Mali

Location

Related Publications (7)

• Seder RA, Chang LJ, Enama ME, Zephir KL, Sarwar UN, Gordon IJ, Holman LA, James ER, Billingsley PF, Gunasekera A, Richman A, Chakravarty S, Manoj A, Velmurugan S, Li M, Ruben AJ, Li T, Eappen AG, Stafford RE, Plummer SH, Hendel CS, Novik L, Costner PJ, Mendoza FH, Saunders JG, Nason MC, Richardson JH, Murphy J, Davidson SA, Richie TL, Sedegah M, Sutamihardja A, Fahle GA, Lyke KE, Laurens MB, Roederer M, Tewari K, Epstein JE, Sim BK, Ledgerwood JE, Graham BS, Hoffman SL; VRC 312 Study Team. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science. 2013 Sep 20;341(6152):1359-65. doi: 10.1126/science.1241800. Epub 2013 Aug 8.

  PMID: 23929949 BACKGROUND

• Sissoko MS, Healy SA, Katile A, Omaswa F, Zaidi I, Gabriel EE, Kamate B, Samake Y, Guindo MA, Dolo A, Niangaly A, Niare K, Zeguime A, Sissoko K, Diallo H, Thera I, Ding K, Fay MP, O'Connell EM, Nutman TB, Wong-Madden S, Murshedkar T, Ruben AJ, Li M, Abebe Y, Manoj A, Gunasekera A, Chakravarty S, Sim BKL, Billingsley PF, James ER, Walther M, Richie TL, Hoffman SL, Doumbo O, Duffy PE. Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial. Lancet Infect Dis. 2017 May;17(5):498-509. doi: 10.1016/S1473-3099(17)30104-4. Epub 2017 Feb 16.

  PMID: 28216244 BACKGROUND

• Hoffman SL, Billingsley PF, James E, Richman A, Loyevsky M, Li T, Chakravarty S, Gunasekera A, Chattopadhyay R, Li M, Stafford R, Ahumada A, Epstein JE, Sedegah M, Reyes S, Richie TL, Lyke KE, Edelman R, Laurens MB, Plowe CV, Sim BK. Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria. Hum Vaccin. 2010 Jan;6(1):97-106. doi: 10.4161/hv.6.1.10396. Epub 2010 Jan 21.

  PMID: 19946222 BACKGROUND

• Sirima SB, Ouedraogo A, Tiono AB, Kabore JM, Bougouma EC, Ouattara MS, Kargougou D, Diarra A, Henry N, Ouedraogo IN, Billingsley PF, Manoj A, Abebe Y, Kc N, Ruben A, Richie TL, James ER, Joshi S, Shrestha B, Strauss K, Lyke KE, Plowe CV, Potter GE, Cox C, Jones W, Sim BKL, Hoffman SL, Laurens MB. A randomized controlled trial showing safety and efficacy of a whole sporozoite vaccine against endemic malaria. Sci Transl Med. 2022 Dec 7;14(674):eabj3776. doi: 10.1126/scitranslmed.abj3776. Epub 2022 Dec 7.

  PMID: 36475905 BACKGROUND

• Mordmuller B, Sulyok Z, Sulyok M, Molnar Z, Lalremruata A, Calle CL, Bayon PG, Esen M, Gmeiner M, Held J, Heimann HL, Woldearegai TG, Ibanez J, Flugge J, Fendel R, Kreidenweiss A, Kc N, Murshedkar T, Chakravarty S, Riyahi P, Billingsley PF, Church LWP, Richie TL, Sim BKL, Hoffman SL, Kremsner PG. A PfSPZ vaccine immunization regimen equally protective against homologous and heterologous controlled human malaria infection. NPJ Vaccines. 2022 Aug 23;7(1):100. doi: 10.1038/s41541-022-00510-z.

  PMID: 35999221 BACKGROUND

• Sissoko MS, Healy SA, Katile A, Zaidi I, Hu Z, Kamate B, Samake Y, Sissoko K, Mwakingwe-Omari A, Lane J, Imeru A, Mohan R, Thera I, Guindo CO, Dolo A, Niare K, Koita F, Niangaly A, Rausch KM, Zeguime A, Guindo MA, Bah A, Abebe Y, James ER, Manoj A, Murshedkar T, Kc N, Sim BKL, Billingsley PF, Richie TL, Hoffman SL, Doumbo O, Duffy PE. Safety and efficacy of a three-dose regimen of Plasmodium falciparum sporozoite vaccine in adults during an intense malaria transmission season in Mali: a randomised, controlled phase 1 trial. Lancet Infect Dis. 2022 Mar;22(3):377-389. doi: 10.1016/S1473-3099(21)00332-7. Epub 2021 Nov 18.

  PMID: 34801112 BACKGROUND

• Diawara H, Healy SA, Mwakingwe-Omari A, Issiaka D, Diallo A, Traore S, Soumbounou IH, Gaoussou S, Zaidi I, Mahamar A, Attaher O, Fried M, Wylie BJ, Mohan R, Doan V, Doritchamou JYA, Dolo A, Morrison RD, Wang J, Hu Z, Rausch KM, Zeguime A, Murshedkar T, Kc N, Sim BKL, Billingsley PF, Richie TL, Hoffman SL, Dicko A, Duffy PE; PfSPZ Vaccine Study Team. 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 Dec;24(12):1366-1382. doi: 10.1016/S1473-3099(24)00360-8. Epub 2024 Aug 14.

  PMID: 39153490 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Patrick E. Duffy
• Organization: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health

patrick.duffy@nih.gov

301.761.5089

Study Officials

• Patrick E Duffy, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: June 18, 2019
• Study Start: July 3, 2019
• Primary Completion: April 5, 2022
• Study Completion: March 17, 2023
• Last Updated: March 19, 2024
• Results First Posted: March 19, 2024

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)