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AzTrials

MalariaPhase 1NCT02627456

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

A Phase 1 study testing PfSPZ Vaccine, PfSPZ Challenge Material and PBS and HSA Diluent in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 years
Conditions the study is for
Malaria
What is being tested?
PfSPZ Vaccine, PfSPZ Challenge Material and PBS and HSA Diluent
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
409 participants
Where
1 siteMali
Study dates
9 Dec 2015to 3 Jul 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
Show all 17Show fewer
  • 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
  • Available for the duration of the study
  • 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.

Who cannot join

  • 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)
Show all 43Show fewer
  • Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B (HBV)
  • Known or documented sickle cell disease by history (Note: known sickle cell trait is NOT exclusionary)
  • 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
  • Known immunodeficiency syndrome
  • Known asplenia or functional asplenia
  • 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
  • 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
  • Receipt of immunoglobulins and/or blood products within the past 6 months
  • Previous receipt of an investigational malaria vaccine in the last 5 years
  • Known allergies or contraindication against: ASAQ or Coartem
  • 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.
  • Subjects must
  • Known to be pregnant by history or as determined by a positive urine or serum human choriogonadotropin (Beta-hCG) test (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)
  • Known or documented sickle cell disease by history (Note: known sickle cell trait is NOT exclusionary)
  • Receipt of artemether/lumefantrine within less than 14 days from enrollment.
  • 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)
  • 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
  • Enrollment in another investigational trial during the study period (participating in screening for other investigational trials is permitted).
  • Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
  • 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
  • Known immunodeficiency syndrome
  • Known asplenia or functional asplenia
  • 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
  • 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.

Trial locations and contacts

1 site in 1 country.

Mali1 site

  • University of Bamako (USTTB/MRTC)

    Bamako

Other trials in Mali

About this study

Official title: Dose Escalating and Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) in Healthy African Adults in Mali

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.

Read more

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.

Read the detailed 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 (Hoffman et al., 2010). 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 (Seder et al., 2013). 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. (Sissoko et al., unpublished) 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. PfSPZ Vaccinees (Arm 2) from the main study will be re enrolled the following malaria transmission along with age, sex, and village matched controls (re enrolled Arm 3, additional controls) to explore the duration of protection through another malaria transmission season.

Subjects will be recruited from rural villages in Mali. The study will be conducted as collaboration among MRTC, LMIV/NIAID, and Sanaria, Inc.

Conditions
Malaria
Being tested
PfSPZ Vaccine, PfSPZ Challenge Material, PBS and HSA Diluent, Normal Saline, Coartem
Keywords
Malaria, Cryopreserved, Infection, Human, Immunization
Medical subject headings
Malaria, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PfSPZ VaccineBiological

    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.

  • PfSPZ Challenge MaterialBiological

    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.

  • PBS and HSA DiluentDrug

    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).

  • Normal SalineOther

    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.

  • CoartemDrug

    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.

  • ASAQDrug

    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.

Study groups in NCT02627456
Study groupRoleWhat they receive
1AExperimental(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.
Receives: Biological: PfSPZ Vaccine; Drug: PBS and HSA Diluent; Drug: ASAQ
1BExperimental(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
Receives: Biological: PfSPZ Vaccine; Drug: PBS and HSA Diluent; Drug: ASAQ
1CExperimental(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.
Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge Material; Drug: PBS and HSA Diluent; Drug: ASAQ
1DExperimental(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.
Receives: Biological: PfSPZ Challenge Material; Drug: PBS and HSA Diluent; Drug: ASAQ
2Experimental(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.
Receives: Biological: PfSPZ Vaccine; Drug: PBS and HSA Diluent; Drug: Coartem; Drug: ASAQ
3Placebo 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.
Receives: Other: Normal Saline; Drug: ASAQ
4Active 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
Receives: Drug: Coartem

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Duration

    1. 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)

    Measured: For 24 weeks starting approximately 1 year post vaccination #3

  2. 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.

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

Secondary outcomes (2)

  1. Protective Efficacy (pilot phase)

    1. falciparum blood stage infection defined as detection of at least 2 P. falciparum parasites by microscopic examination of 0.5 (Micro)L starting immediately following PfSPZ CHMI(Arms lc, ld)

    Measured: Immediately following PfSPZ CHMI

  2. Protective Efficacy (main phase)

    1. falciparum blood stage infection defined as detection of at least 2 P. falciparum parasites by microscopic examination of 0.5 muL starting immediately following Vaccination #3 (Arms 2, 3)

    Measured: Immediately following 3rd vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2015 (estimated)
  2. Study start9 Dec 2015
  3. Primary completion31 Mar 2018
  4. Study completion3 Jul 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
409 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02627456
Sponsor's protocol ID
999916004
Other IDs
16-I-N004
Status last verified
Apr 2021
First submitted
9 Dec 2015
Last updated
21 Apr 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 19946222

  • 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.

    PubMed 25889522

  • 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.

    PubMed 23929949

  • 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.

    PubMed 34801112

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PfSPZ Vaccine, PfSPZ Challenge Material and PBS and HSA Diluent in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Duration (time frame: For 24 weeks starting approximately 1 year post vaccination #3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02627456, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2021.

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