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

NCT03510481 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 99991808418-I-N084
• Study Type: interventional
• Target: 478
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The disease malaria affects many people in Mali and other parts of Africa and the world. It is caused by germs spread by mosquito bites. Malaria may be mild. But it can also be serious or lead to death if it is not treated promptly. Researchers want to find a safe vaccine that prevents malaria. Objective: To study how safe and tolerable the malaria vaccine called PfSPZ Vaccine is for healthy adults. Eligibility: Healthy adults:

• ages 18-35 in Ouelessebougou, Mali
• not infected with HIV, hepatitis B, or hepatitis C
• for females, not pregnant or breastfeeding and must use reliable birth control during the study Design: Participants will be screened with questions about malaria and will undergo blood, urine, and heart tests. Participants will be randomly assigned to 1 of 4 groups. They will get injections of either the PfSPZ Vaccine or a salt-water placebo. They will not know which one they get. Vaccinations will occur leading into the malaria transmission each year with 3 injections leading into Year 1 (malaria transmission season in 2018) and 1 injection prior to Year 2 (malaria transmission season 2019). One vaccine group and one placebo group will get an injection 3 times over 4 weeks with an additional vaccination \~10 months later. The other two groups (vaccine group and placebo) will get an injection 3 times over 16 weeks with an additional vaccination \~10 months later. All participants will be treated with an antimalarial medication prior to the third injection and prior to fourth injection. They will be followed for approximately 6 months after third and fourth injection. At vaccine visits, female participants will have a pregnancy test before injection. All participants will have an arm cleaned and the vaccine injected in a vein. They will be watched for 30 minutes. At non-vaccine visits, participants will have a physical exam and be asked how they are feeling. They will usually have blood tests.

Conditions

Malaria

Keywords

PfSPZ Vaccine; Malaria; Plasmodium falciparum

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Local and Systemic Adverse Events in Year One

  Incidence of local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine administration in year one

  Within 7 days after each vaccination in year one

• Number of Participants With Local and Systemic Adverse Events in Year Two

  Incidence of local and systemic adverse events (AEs) graded by severity occurring within 7 days after vaccine administration during year two (booster dose)

  Within 7 days after each vaccination in year two

Study Arms (4)

Experimental arm 1: Dosing interval 0, 8, 16, and 54 weeks

EXPERIMENTAL

Participants received 3 doses of PfSPZ Vaccine (9 x 10\^5) via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.

Biological: PfSPZ Vaccine; Drug: artemether 20mg/lumefantrine 120mg (AL)

Experimental arm 2: Dosing interval 0, 1, 4, and 42 weeks

EXPERIMENTAL

Participants received 3 doses of PfSPZ Vaccine (9 x 10\^5) via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.

Biological: PfSPZ Vaccine; Drug: artemether 20mg/lumefantrine 120mg (AL)

Placebo comparator 3a: Dosing interval 0, 8, 16, and 54 weeks

PLACEBO COMPARATOR

Control for Arm 1. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.

Drug: Normal Saline; Drug: artemether 20mg/lumefantrine 120mg (AL)

Placebo comparator 3b: Dosing interval 0, 1, 4, and 42 weeks

PLACEBO COMPARATOR

Control for Arm 2. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.

Drug: Normal Saline; Drug: artemether 20mg/lumefantrine 120mg (AL)

Interventions

PfSPZ Vaccine BIOLOGICAL

PfSPZ Vaccine is Radiation attenuated, aseptic, purified, vialed, cryopreserved, NF54 P. falciparum sporozoites produced by Sanaria, Inc.

Experimental arm 1: Dosing interval 0, 8, 16, and 54 weeks; Experimental arm 2: Dosing interval 0, 1, 4, and 42 weeks

Normal Saline DRUG

Clear liquid indistinguishable from the study product will be used as a placebo rather than a comparator vaccine.

Placebo comparator 3a: Dosing interval 0, 8, 16, and 54 weeks; Placebo comparator 3b: Dosing interval 0, 1, 4, and 42 weeks

artemether 20mg/lumefantrine 120mg (AL) DRUG

Licensed antimalarial in the US and Mali for use for uncomplicated malaria.

Also known as: Coartem

Experimental arm 1: Dosing interval 0, 8, 16, and 54 weeks; Experimental arm 2: Dosing interval 0, 1, 4, and 42 weeks; Placebo comparator 3a: Dosing interval 0, 8, 16, and 54 weeks; Placebo comparator 3b: Dosing interval 0, 1, 4, and 42 weeks

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age greater than or equal to 18 and less than or equal to 35 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
• Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to Study Day 1 to 28 days after last vaccination.
• Reliable methods of birth control include:
• one of the following: confirmed pharmacologic contraceptives (parenteral) delivery; intrauterine or implantable device. OR
• two of the following: a documented oral or transdermal or vaginal ring contraceptives; PLUS condoms with spermicide or diaphragm with spermicide.
• Note, Coartem (artemether specifically) may reduce the effectiveness of systemic hormonal contraceptives, therefore additional barrier methods such as condoms must also be used during the 3 days of Coartem dosing.
• Women who are not able to get pregnant 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 urine or serum pregnancy test performed per protocol.

You may not qualify if:

• Pregnancy, as determined by a positive urine or serum human chorionic gonadotropin (beta-hCG) test (if female). NOTE: Pregnancy is also a criterion 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 (Hb), 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)
• 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)
• Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B (HBV)
• Clinically significant abnormal electrocardiogram (ECG) such as abnormal 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 3 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
• Sanaria Inc.: collaborator
• Malaria Research and Training Center, Bamako, Mali: collaborator

Study Sites (1)

Malaria Research and Training Center

Bamako, Mali

Location

Related Publications (3)

• 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

• Jongo SA, Church LWP, Mtoro AT, Schindler T, Chakravarty S, Ruben AJ, Swanson PA, Kassim KR, Mpina M, Tumbo AM, Milando FA, Qassim M, Juma OA, Bakari BM, Simon B, James ER, Abebe Y, Kc N, Saverino E, Fink M, Cosi G, Gondwe L, Studer F, Styers D, Seder RA, Schindler T, Billingsley PF, Daubenberger C, Sim BKL, Tanner M, Richie TL, Abdulla S, Hoffman SL. Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults. Clin Infect Dis. 2020 Dec 31;71(11):2849-2857. doi: 10.1093/cid/ciz1152.

  PMID: 31782768 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; Malaria, Falciparum

Interventions

Saline Solution; Artemether; Lumefantrine; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Drug Combinations

Results Point of Contact

• Title: Dr. Patrick Duffy
• Organization: NIAID/LMIV

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: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: April 27, 2018
• Study Start: May 14, 2018
• Primary Completion: November 23, 2019
• Study Completion: February 13, 2020
• Last Updated: August 20, 2021
• Results First Posted: August 20, 2021

Record last verified: 2021-05

Locations

MA (1)