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

• Status: Completed
• Trial end date: 2018-07-03
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Artemether, Lumefantrine Drug Combination; Vaccines

Criteria

• INCLUSION CRITERIA PILOT and MAIN STUDY:

Subjects must fulfill all the following criteria to be eligible for the pilot and main study:

1. Age greater than or equal to 18 and less than or equal to 50 years

2. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process

3. In good general health and without clinically significant medical history

4. Willing to have blood samples stored for future research

5. Available for the duration of the study

6. 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.

INCLUSION CRITERIA DURATION STUDY:

Subjects must fulfill all the following criteria to be eligible for the duration study:

1. Age greater than or equal to 18 and less than or equal to 52 years

2. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process

3. In good general health and without clinically significant medical history

4. Willing to have blood samples stored for future research

5. Available for the duration of the study

6. Participated in the main phase of this protocol (Arms 2,3) AND received all three vaccinations OR suitable to serve as a matched control for such an individual.

EXCLUSION CRITERIA PILOT and MAIN STUDY:

A subject will be excluded from participating in the pilot or main trial if any one of the following criteria is fulfilled:

1. Pregnancy, as determined by a positive urine or serum human choriogonadotropin (beta-hCG) test (if female)

2. Currently breast-feeding (if female)

3. 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

4. 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)

5. 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)

6. Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B (HBV)

7. Known or documented sickle cell disease by history (Note: known sickle cell trait is NOT exclusionary)

8. Clinically significant abnormal ECG

9. 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

10. History of receiving any investigational product within the past 30 days

11. 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

12. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.

13. History of a severe allergic reaction or anaphylaxis

14. 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.

15. 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

16. Known immunodeficiency syndrome

17. Known asplenia or functional asplenia

18. Use of:

• Chronic (greater than or equal to 14 days) oral or intravenous corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of vaccination

• Use of antimalarials or systemic antibiotics with known antimalarial activity within 30 days prior to the first vaccine

19. Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to Vaccination #1 and every subsequent vaccination day

20. Receipt of immunoglobulins and/or blood products within the past 6 months

21. Previous receipt of an investigational malaria vaccine in the last 5 years

22. Known allergies or contraindication against: ASAQ or Coartem

23. Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a participant participating in the trial, interfere with the evaluation of the study objectives, or would render the subject unable to comply with the protocol.

EXCLUSION CRITERIA DURATION STUDY:

Subjects must

1. Known to be pregnant by history or as determined by a positive urine or serum human choriogonadotropin (Beta-hCG) test (if female)

2. 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

3. 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)

4. 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)

5. Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B (HBV)

6. Known or documented sickle cell disease by history (Note: known sickle cell trait is NOT exclusionary)

7. Receipt of artemether/lumefantrine within less than 14 days from enrollment.

8. Knwn allergies or contraindications (such as significant cardiac disease; prolonged QTc greater than 450 ms; currently taking medications that may prolong your QTc; serious side effects from artemether/lumefantrine in the past) to study treatment (artemether/lumefantrine)

9. 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

10. Enrollment in another investigational trial during the study period (participating in screening for other investigational trials is permitted).

11. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.

12. 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

13. Known immunodeficiency syndrome

14. Known asplenia or functional asplenia

15. Use of Chronic (greater than or equal to 14 days) oral or intravenous corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of Study Day 0

16. Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a participant participating in the trial, interfere with the evaluation of the study objectives, or would render the subject unable to comply with the protocol.