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

• Status: Completed
• Trial end date: 2020-02-13
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Malaria Research and Training Center, Bamako, Mali; Sanaria Inc.
• Treatments: Artemether; Artemether-lumefantrine combination; Artemisinins; Lumefantrine; Vaccines

Criteria

• INCLUSION CRITERIA:

1. Age greater than or equal to 18 and less than or equal to 35 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 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.

EXCLUSION CRITERIA:

1. 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.

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 (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)

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 electrocardiogram (ECG) such as abnormal QTc.

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(Grade 3 or higher or per PI discretion) or anaphylaxis

14. 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)

15. 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

16. Known immunodeficiency syndrome

17. Known asplenia or functional asplenia

18. Use of:

• Chronic (greater than or equal to 14 days) oral or IV 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 5 drug half-lives prior to the first vaccine (such as artemether, artemether-lumefantrine, sulfadoxine-pyrimethamine, trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones or azithromycin)

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

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

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

22. Known allergies or other contraindications against 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