NCT01988636

Brief Summary

Background: \- Malaria is caused by small germs carried by mosquitoes. People can get malaria if an infected mosquito bites them. Malaria destroys red blood cells and reduces oxygen in the blood. Most malaria is mild, but severe malaria kills at least 660,000 people each year. About 75% of these are children in Sub-Saharan Africa, most under age 5. Researchers want to find a safe vaccine that helps prevent malaria. Objectives: \- To see if a new malaria vaccine is well tolerated and effective. Eligibility: \- Healthy adults 18 35 years old who are not pregnant and live in Mali. Design:

  • Participants will be screened with medical history, physical exam, and blood test. They will also have an ECG. Soft electrodes will be stuck to the skin. A machine will record the heart s electrical signals.
  • Study participation will last about 1 year.
  • Participants will be randomly placed in 5 groups. Some will get 2 doses of the PfSPZ vaccine weeks apart; some will get 3 or 5 doses of vaccine; some will get 3 or 5 doses of placebo.
  • Doses will be given through a needle in the arm directly into the bloodstream. Then participants must stay at the clinic for 2 hours.
  • After each dose, participants will return to the clinic several times for blood tests and physical exam.
  • A week before the first dose and 2 weeks after the last, participants will take a full course of anti-malaria drugs.
  • If a participant gets malaria during the study, they will take another course of anti-malaria drugs.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
296

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Oct 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 29, 2013

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

November 9, 2013

Completed
11 days until next milestone

First Posted

Study publicly available on registry

November 20, 2013

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 20, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 20, 2015

Completed
Last Updated

December 3, 2019

Status Verified

August 20, 2015

Enrollment Period

1.8 years

First QC Date

November 9, 2013

Last Update Submit

November 30, 2019

Conditions

Malaria

Keywords

RandomizedDouble BlindedMaliMalariaTransmission

Outcome Measures

Primary Outcomes (1)

  • Assess the safety of repeated IV immunizations with PfSPZ Vaccine

    28 days

Study Arms (3)

Group 1

EXPERIMENTAL

Pilot Safety Group- 135000 PfSPZ + 270000 PfSPZ; staggered at Day 0 and 2 weeks

Biological: PfSPZ Vaccine

Group 4

ACTIVE COMPARATOR

Group to start at week 4 after Group 1 is deemed safe - 5 immunizations of 270000 PfSPZ at weeks 4, 8, 12, 16 and 24

Biological: PfSPZ Vaccine

Group 5

PLACEBO COMPARATOR

Group to receive placebo at same points as Group 4 - 5 immunizations of normal saline at weeks 4, 8, 12, 16 and 24

Drug: Placebo

Interventions

PfSPZ VaccineBIOLOGICAL

Aseptic, purified, vialed, cryopreserved, radiation attenuated NF54 p.falciparum sporozoites produced by Sanaria, Inc.

Group 1Group 4
PlaceboDRUG

Placebo

Group 5

Eligibility Criteria

Age18 Years - 35 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • The subject must satisfy all the following criteria to be eligible for the study:
  • Signed informed consent form (ICF)
  • Aged 18 to 35 years
  • Long term resident of study site (living there for at least 4 years)
  • Willingness to remain resident in the village and to abstain from travel for prolonged periods during the study
  • Willingness to take a curative anti-malarial regimen when prescribed by the investigator
  • Willingness to provide blood for safety data.
  • For females: agreement to use reliable contraception (in the setting where this trial takes place documented depot injection of contraceptives, surgical sterilization ; or an implanted device (all with written evidence provided by an appropriately trained physician) is considered reliable contraception) for the duration of the vaccination phase (i.e., from 1 month prior to first vaccination until 1 month after last vaccination)
  • For females: negative pregnancy test at screening and before each vaccination; women found pregnant will not be given subsequent doses but will be followed up for safety reasons

You may not qualify if:

  • Use of antimalarials (other than that prescribed by the investigator) or systemic antibiotics with known antimalarial activity within 30 days prior to the first vaccine dose (e.g. Trimethoprim-Sulfamethoxazole, Doxycycline, Tetracycline, Clindamycin, Erythromycin, Fluoroquinolones, or Azithromycin)
  • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
  • Prior receipt of a malaria vaccine candidate
  • Recurrent, severe infections other than malaria, and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
  • Use of immunoglobulins or blood products within 3 months prior to enrolment
  • A history of allergic disease or significant reactions against mosquito bites
  • Known allergies or contraindications against Artemether/Lumefantrine, or
  • Atovaquone/Proguanil, such as:
  • Concurrent medication with Neuroleptics, Antidepressants (i.e., Imipramine, Amitryptilline, Clomipramine and others), Drugs used to treat tuberculosis, including Rifampicin and Rifabutine, Macrolide antibiotics (i.e., Erythromycin, Clarithromycin, Azithromycin, Roxitromycin), Fluoroquinolones (i.e., Ciprofloxacin, Moxifloxacin, Levofloxacin), Antimykotics (i.e., Ketoconazole, Itraconazole), Cimetidine, Class IA and class III antiarrhythmics (i.e., Quinidine, Ajmalin, Disopyramid, Amiodaron, Sotalol), Flecainid, Metoprolol, Cisaprid, Terfenadin, Astemizole, and Metoclopramide
  • Renal impairment
  • Symptoms of low potassium, and/or low magnesium
  • A family history of sudden cardiac death, which in the opinion of the investigator was caused by a pre-existing arrhythmia
  • Known diagnosis or family history of long QT syndrome
  • Heart disease (i.e., heart failure, arrhythmias)
  • History of cancer (except basal cell carcinoma)
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Bamako

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: 19946222BACKGROUND

  • 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: 23929949BACKGROUND

  • Epstein JE, Tewari K, Lyke KE, Sim BK, Billingsley PF, Laurens MB, Gunasekera A, Chakravarty S, James ER, Sedegah M, Richman A, Velmurugan S, Reyes S, Li M, Tucker K, Ahumada A, Ruben AJ, Li T, Stafford R, Eappen AG, Tamminga C, Bennett JW, Ockenhouse CF, Murphy JR, Komisar J, Thomas N, Loyevsky M, Birkett A, Plowe CV, Loucq C, Edelman R, Richie TL, Seder RA, Hoffman SL. Live attenuated malaria vaccine designed to protect through hepatic CD8(+) T cell immunity. Science. 2011 Oct 28;334(6055):475-80. doi: 10.1126/science.1211548. Epub 2011 Sep 8.

    PMID: 21903775BACKGROUND

  • 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: 28216244DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Study Officials

  • Sara A Healy, 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
FACTORIAL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 9, 2013

First Posted

November 20, 2013

Study Start

October 29, 2013

Primary Completion

August 20, 2015

Study Completion

August 20, 2015

Last Updated

December 3, 2019

Record last verified: 2015-08-20

Locations

MA(1)