Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites in Healthy African Adults in Mali

NCT02627456 | Completed Phase 1 FDA Drug

• 2 other identifiers: 99991600416-I-N004
• Study Type: interventional
• Target: 409
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Malaria is still a health problem in Sub-Saharan Africa. Death rates are stable and have even increased in some areas. There are malaria vaccines. However, researchers think repeated immunizations with a vaccine called PfSPZ may work better. Objective: To see if PfSPZ is safe, tolerable, and effective against malaria. Eligibility: Healthy adults ages 18 to 50 years who live in the Doneguebougou area in Mali Design: Participants will be screened with medical history and physical exam. Participants will sign or fingerprint the consent form. They will take a survey to see how well they understand the study. Participants will give blood and urine samples. Participants will have at least one ECG: Soft electrodes will be stuck to the skin. A machine will record heart signals. Participants will have HIV counseling. Participants will be assigned to a group. Groups will get a different strength doses. Groups will get a different number of vaccines over different periods of time. If a participant develops a rash or injection site reaction, photographs may be taken. Participants will receive an oral anti-malaria drug during the study. Participants will be monitored for 3 to 6 months after the last vaccine.

Conditions

Malaria

Keywords

Malaria; Cryopreserved; Infection; Human; Immunization

Outcome Measures

Primary Outcomes (2)

• Duration

  P. falciparum blood stage infection defined as time to first positive blood smear (detection of at least 2 P. falciparum parasites by microscopic examination of 0.5 muL)

  For 24 weeks starting approximately 1 year post vaccination #3

• Safety

  Measure the incidence and severity of local and systemic adverse events occurring within 7 days after each vaccine administration and SAE related to vaccination.

  Approximately within 7 days after each vaccination and SAEs related to vaccination

Secondary Outcomes (2)

• Protective Efficacy (pilot phase)

  Immediately following PfSPZ CHMI

• Protective Efficacy (main phase)

  Immediately following 3rd vaccination

Study Arms (7)

1A

EXPERIMENTAL

(n=5), will be a safety group. Subjects will receive 1 dose of PfSPZ Vaccine (4.5x105) via DVI. All 5 subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to PfSPZ Vaccine. Subjects will be followed for approximately 3 months post vaccination.

Biological: PfSPZ Vaccine; Drug: PBS and HSA Diluent; Drug: ASAQ

1B

EXPERIMENTAL

(n=S), will be a safety group. Subjects will receive 1 dose of PfSPZ Vaccine (9.0x10S) via DVI. All S subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to PfSPZ Vaccine. Subjects will be followed for approximately 3 months post vaccination

Biological: PfSPZ Vaccine; Drug: PBS and HSA Diluent; Drug: ASAQ

1C

EXPERIMENTAL

(n=30), will be the targeted dose for the Pilot Safety Group. Subjects will receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. 15 subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to each administration of PfSPZ Vaccine, while 15 will not, except prior to PfSPZ Vaccine #3 when all 30 subjects will receive antimalarial treatment with ASAQ.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge Material; Drug: PBS and HSA Diluent; Drug: ASAQ

1D

EXPERIMENTAL

(n=15), will be the CHMI control group. Subjects will not receive any PfSPZ vaccinations but will serve as infectivity controls for CHMI. All 15 subjects will receive antimalarial treatment with ASAQ prior to PfSPZ Challenge.

Biological: PfSPZ Challenge Material; Drug: PBS and HSA Diluent; Drug: ASAQ

2

EXPERIMENTAL

(n=60), will be the targeted vaccine dose arm and receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. All subjects will receive antimalarial treatment prior to Vaccination #1 and #3 unless results obtained and analyzed from the pilot study indicate otherwise.

Biological: PfSPZ Vaccine; Drug: PBS and HSA Diluent; Drug: Coartem; Drug: ASAQ

3

PLACEBO COMPARATOR

(n=60), will be the placebo arm and receive vaccinations with normal saline via DVI on Day 1, 57, 113. All subjects will receive antimalarial treatment prior to Vaccination #1 and #3 unless results obtained and analyzed from the Pilot Study indicate otherwise.

Other: Normal Saline; Drug: ASAQ

4

ACTIVE COMPARATOR

(n=SS), will be group- matched (age, sex, village) controls for Arm 2 for the duration study. Subjects previously enrolled in Arm 3 may re-enroll in Arm 4. All subjects will receive antimalaria treatment at enrollment

Drug: Coartem

Interventions

PfSPZ Vaccine BIOLOGICAL

PfSPZ Vaccine contains aseptic, purified, vialed, cryopreserved, radiation attenuated NF54 P. falciparum sporozoites. PfSPZ Vaccine will be delivered by DVI in the pilot and main phases of the study. Participants will receive either 1 or 3 injections.

1A; 1B; 1C; 2

PfSPZ Challenge Material BIOLOGICAL

PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites used for CHMI trials. PfSPZ Challenge is not radiated, thus it is fully infections. It will be administered via DVI to participants in Arm 1c and 1d.

1C; 1D

PBS and HSA Diluent DRUG

The diluent for PfSPZ Vaccine and Challenge is composed of phosphate-buffered saline (PBS) and human serum albumin (HSA). Vials of sterile PBS (1.6ml) and HSA (0.5ml) will be shipped to the clinical site, where diluent composed of PBS and HSA is prepared. HSA is a licensed product which is approved for parenteral, IV administration to humans. The HSA lots are extensively tested to ensure that it is free of infectious agents as listed in the CoA and is approved for use by the Food and Drug Administration(FDA).

1A; 1B; 1C; 1D; 2

Normal Saline OTHER

Sterile isotonic (0.9%) normal saline will be procured in the US and shipped to Mali at ambient temperature. Like the product, normal saline is a clear liquid, making it indistinguishable from the study product when drawn up into a syringe.

3

Coartem DRUG

Artemether/lumefantrine (coartem) is a licensed antimalarial in the US and Mali for use for uncomplicated malaria. It has an excellent safety profile and is widely used to treat malaria. Artemether /lumefantrine is a Category C pregnancy drug. Thus all female participants will undergo pregnancy testing prior to receiving this drug.

2; 4

ASAQ DRUG

ASAQ is a fixed dose artemisinin based combination therapy that is indicated and approved for the management of uncomplicated P. falciparum malaria. It has been shown to be as effective as artemether /lumefantrine when taken at a once/day dosage.

1A; 1B; 1C; 1D; 2; 3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must fulfill all the following criteria to be eligible for the pilot and main study:
• Age greater than or equal to 18 and less than or equal to 50 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 3 months after the last vaccination.
• Reliable methods of birth control include one of the following: confirmed pharmacologic contraceptives (parenteral) delivery; intrauterine or implantable device.
• Reliable methods of birth control include concurrent use of a pharmacologic and a barrier method, i.e., two of the following: confirmed pharmacological contraceptives (oral, transdermal) delivery or vaginal ring AND condoms with spermicide or diaphragm with spermicide.
• Non-childbearing women 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.
• Subjects must fulfill all the following criteria to be eligible for the duration study:
• Age greater than or equal to 18 and less than or equal to 52 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

You may not qualify if:

• A subject will be excluded from participating in the pilot or main trial if any one of the following criteria is fulfilled:
• Pregnancy, as determined by a positive urine or serum human choriogonadotropin (beta-hCG) test (if female)
• 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, 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 ECG
• 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 or anaphylaxis
• Severe asthma (defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has rquired the use of oral or parenteral corticosteroids at any time during the past 2 years.
• Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sj(SqrRoot)(Delta)gren s syndrome, or autoimmune thrombocytopenia

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Bamako (USTTB/MRTC)

Bamako, Mali

Location

Related Publications (4)

• 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

• Mordmuller B, Supan C, Sim KL, Gomez-Perez GP, Ospina Salazar CL, Held J, Bolte S, Esen M, Tschan S, Joanny F, Lamsfus Calle C, Lohr SJ, Lalremruata A, Gunasekera A, James ER, Billingsley PF, Richman A, Chakravarty S, Legarda A, Munoz J, Antonijoan RM, Ballester MR, Hoffman SL, Alonso PL, Kremsner PG. Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection: a dose-finding trial in two centres. Malar J. 2015 Mar 18;14:117. doi: 10.1186/s12936-015-0628-0.

  PMID: 25889522 BACKGROUND

• 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, 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 DERIVED

MeSH Terms

Conditions

Malaria; Infections

Interventions

Saline Solution; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Patrick E Duffy, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

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: December 9, 2015
• First Posted: December 11, 2015
• Study Start: December 9, 2015
• Primary Completion: March 31, 2018
• Study Completion: July 3, 2018
• Last Updated: April 21, 2021

Record last verified: 2021-04

Locations

MA (1)