Overview

This trial is active, not recruiting.

Condition malaria
Treatments pfspz vaccine, pfspz challenge material, pbs and hsa diluent
Phase phase 1
Sponsor National Institute of Allergy and Infectious Diseases (NIAID)
Start date October 2015
End date January 2017
Trial size 500 participants
Trial identifier NCT02627456, 16-I-N004, 999916004

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose prevention
Arm
(Experimental)
(n=5), will be asafety group.Subjects will receive1 dose of PfSPZVaccine (4.5x105)
pfspz vaccine
PfSPZ Vaccine contains aseptic, purified, cryopreserved, radiation attenuated NF54 P. falciparum sporozoites (PfSPZ) produced and manufactured by Sanaria Inc, located in Rockville, Maryland, USA. It is manufactured in compliance with GMP regulations (21 CFR 211), and USP<71> sterility testing. The diluent for PfSPZ Vaccine and Challenge is composed of phosphate-buffered saline (PBS) and human serum albumin (HSA). PBS was manufactured in compliance with GMP by Sanaria, Inc. HSA is a licensed product approved for parenteral, IV administration to humans.
pbs and hsa diluent
Sterile 0.9% normal saline is commercially procured in the US and shipped to Mali. Normal saline is a clear liquid, making it indistinguishable from the study product.
(Experimental)
n=5), will be asafety group.Subjects will receive1 dose of PfSPZVaccine (9.0x105)via DVI. All 5subjects will receiveantimalarialtreatment withartesunate/amodiaquine (ASAQ) prior toPfSPZ Vaccine.Subjects will befollowed forapproximately 3months postvaccination.
pfspz vaccine
PfSPZ Vaccine contains aseptic, purified, cryopreserved, radiation attenuated NF54 P. falciparum sporozoites (PfSPZ) produced and manufactured by Sanaria Inc, located in Rockville, Maryland, USA. It is manufactured in compliance with GMP regulations (21 CFR 211), and USP<71> sterility testing. The diluent for PfSPZ Vaccine and Challenge is composed of phosphate-buffered saline (PBS) and human serum albumin (HSA). PBS was manufactured in compliance with GMP by Sanaria, Inc. HSA is a licensed product approved for parenteral, IV administration to humans.
pbs and hsa diluent
Sterile 0.9% normal saline is commercially procured in the US and shipped to Mali. Normal saline is a clear liquid, making it indistinguishable from the study product.
(Experimental)
(n=30), will be thetargeted dose forthe primary PilotSafety Group.Subjects will receive3 doses of PfSPZVaccine (18x105)via DVI on Day 1,57, 113. 15 subjectswill receiveantimalarialtreatment withartesunate/amodiaquine (AS/AQ) priorto eachadministration ofPfSPZ Vaccine, while15 will not. All 30subjects will receiveantimalarialtreatment withASAQ prior to PfSPZChallenge.
pfspz vaccine
PfSPZ Vaccine contains aseptic, purified, cryopreserved, radiation attenuated NF54 P. falciparum sporozoites (PfSPZ) produced and manufactured by Sanaria Inc, located in Rockville, Maryland, USA. It is manufactured in compliance with GMP regulations (21 CFR 211), and USP<71> sterility testing. The diluent for PfSPZ Vaccine and Challenge is composed of phosphate-buffered saline (PBS) and human serum albumin (HSA). PBS was manufactured in compliance with GMP by Sanaria, Inc. HSA is a licensed product approved for parenteral, IV administration to humans.
pbs and hsa diluent
Sterile 0.9% normal saline is commercially procured in the US and shipped to Mali. Normal saline is a clear liquid, making it indistinguishable from the study product.
(Experimental)
(n=15), will be theCHMI control group.Subjects will notreceive any PfSPZvaccinations but willserve as infectivitycontrols for CHMI.All 10 subjects willreceive antimalarialtreatment withASAQ prior to PfSPZ challenge
pfspz vaccine
PfSPZ Vaccine contains aseptic, purified, cryopreserved, radiation attenuated NF54 P. falciparum sporozoites (PfSPZ) produced and manufactured by Sanaria Inc, located in Rockville, Maryland, USA. It is manufactured in compliance with GMP regulations (21 CFR 211), and USP<71> sterility testing. The diluent for PfSPZ Vaccine and Challenge is composed of phosphate-buffered saline (PBS) and human serum albumin (HSA). PBS was manufactured in compliance with GMP by Sanaria, Inc. HSA is a licensed product approved for parenteral, IV administration to humans.
pfspz challenge material
PfSPZ Challenge are live and infectious aseptic, purified, cryopreserved NF54 P.falciparum sporozoites. PfSPZ Challenge is manufactured identical to PfSPZ Vaccine without irradiation.
pbs and hsa diluent
Sterile 0.9% normal saline is commercially procured in the US and shipped to Mali. Normal saline is a clear liquid, making it indistinguishable from the study product.

Primary Outcomes

Measure
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.
time frame: Approximately 7 days after each vaccination

Secondary Outcomes

Measure
(Protective Efficacy)P. falciparum blood stage infection defined asdetection of at least 2 P. falciparum parasites by microscopic examination of 0.5 L starting immediately following PfSPZ CHMI (Arms 1c, 1d) [PILOT STUDY]
time frame: Immediately following PfSPZ CHMI
(Protective Efficacy)P. falciparum blood stage infection defined asdetection of at least 2 P. falciparum parasites by microscopic examination of 0.5 L starting immediately following Vaccination #3 (Arms 2, 3) [MAIN STUDY]
time frame: Immediately following 3rd vaccination

Eligibility Criteria

Male or female participants from 18 years up to 50 years old.

- INCLUSION CRITERIA: 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 from 21 days prior to Study Day 1 to 3 months after the last vaccination. EXCLUSION CRITERIA: 1. Pregnancy, as determined by a positive urine or serum human choriogonadotropin 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 5. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal 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 PfSPZ Vaccine in Mali, Africa- Dose Escalation 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 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.

Additional Information

Official title Dose Escalating and Randomized, Placebo-Controlled, Double-Blind Study to Assess Safaty, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) in Healthy African Adults in Mali
Principal investigator Sara A Healy, M.D.
Description It is known that humans can be protected against malaria by repeated immunization with radiation-attenuated sporozoites. Traditionally, those sporozoites are administered by exposing the vaccinee to at least 1000 bites of sporozoite-infected irradiated mosquitoes, an approach that is unsuitable for mass vaccination campaigns. Recently, Sanaria, Inc. developed a process for manufacturing, in compliance with current Good Manufacturing Practices (cGMPs) aseptic, purified, radiation attenuated cryopreserved sporozoites from a well-characterized isolate of P. falciparum. This product, which is called PfSPZ Vaccine, can be administered by needle and syringe. Previous studies conducted by the Vaccine Research Center and the Navy have established that IV administration of PfSPZ Vaccine can induce sterile protection against controlled human malaria infection (CHMI) with a homologous strain of P. falciparum in up to 100% of malaria na(SqrRoot) ve individuals. A recent study conducted as collaboration among the Malaria Research and Training Center (MRTC, Mali), the Laboratory of Malaria Immunology and Vaccinology (LMIV) National Institute of Allergy and Infectious Diseases (NIAID), and Sanaria, Inc. has shown that sterile protection against naturally occurring malaria infection can be achieved, but not at the level seen in the US nor at the level desired. The next logical step in an attempt to improve protective efficacy in the targeted endemic population is to increase the PfSPZ Vaccine dose, increasing the interval between the first and second doses to 8 weeks (as was done in WRAIR 2080 in the group receiving 3 doses of 4.5x105 PfSPZ), and reducing the numbers of doses to three. Additionally, in this study design, we also can begin to understand how the standard controlled human malaria infection (CHMI) model may be used in the field and start to explore the impact of such factors as malaria co-infection and drug treatment have on vaccine responses. The initial dose escalation pilot study will focus on safety and tolerability of the PfSPZ Vaccine. A defined number of subjects enrolled during the pilot study will also undergo further evaluation, including randomization to receive or not receive drug treatment immediately prior to each vaccination and examination of protective efficacy against homologous CHMI via PfSPZ Challenge. The targeted dose (18x105 PfSPZ Vaccine), if safe and tolerable, will be administered to a larger cohort in a double blind, randomized, placebo controlled trial to examine the protective efficacy of the vaccine against naturally occurring infection. Subjects will be recruited from rural villages in Mali. The study will be conducted as collaboration among MRTC, LMIV/NIAID, and Sanaria, Inc.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by National Institutes of Health Clinical Center (CC).