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MalariaPhase 2NCT03989102

Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Malaria Transmission Season in Healthy African Adult Women of Childbearing Potential in Mali

A Phase 2 study testing PfSPZ Vaccine and Normal Saline 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
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Trial summary

Background: Malaria is a disease spread by mosquitos. Pregnant women are highly susceptible to malaria. This can lead to poor health outcomes for pregnant women and their babies. Researchers want to test a malaria vaccine in women of child bearing potential (WOCBP) and pregnant women. This has not been done before. Read more about this study

Who is it for?
Ages Up to 38 years
Conditions the study is for
Malaria
What is being tested?
PfSPZ Vaccine and Normal Saline
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
324 participants
Where
1 siteMali
Study dates
3 Jul 2019to 17 Mar 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Up to 38 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Females of child bearing potential aged greater than or equal to 18 and less than or equal to 38 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
  • Must be willing to use reliable contraception (defined as: pharmacologic contraceptives [parental delivery] or pre-existing intrauterine or implantable device) from 21 days prior to study day 1 to 28 days after last vaccination
  • Report being interested in becoming pregnant within the next 1-2 years

Who cannot join

  • Pregnancy at the time of enrollment/vaccination, as determined by a positive urine or serum human chorionic gonadotropin (beta-hCG) test
  • Biologically unable to become pregnant secondary to: surgical sterilization, premature ovarian insufficiency (defined as no menses for greater than or equal to 12 months without an alternative medical cause)
  • 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 (Hgb), white blood cell count (WBC), absolute neutrophils, and platelets outside the local laboratory-defined limits of normal and greater than or equal to Grade 2 (subjects may be included at the investigators discretion for not clinically significant abnormal values)
  • Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal and greater than or equal to Grade 2 (subjects may be included at the investigators discretion for not clinically significant abnormal values)
  • Infected with human immunodeficiency virus (HIV)
Show all 23Show fewer
  • Known or documented sickle cell disease by history (Note: known sickle cell trait is NOT exclusionary)
  • Clinically significant abnormal electrocardiogram (ECG) such as abnormal corrected QT interval (QTc).
  • 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 (Grade 2 or higher or per PI discretion) or anaphylaxis
  • 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)
  • 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
  • Known immunodeficiency syndrome
  • Known asplenia or functional asplenia
  • Use of chronic (greater than or equal to 14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone greater than or equal to 20 mg/day) or immunosuppressive drugs within 30 days of vaccination
  • 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
  • Receipt of immunoglobulins and/or blood products within the past six months
  • Previous receipt of an investigational malaria vaccine in the last five years
  • Known allergies or other contraindications against use of artemeter/lumefantrine
  • 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

  • Ouelessebougou Health Research Unit

    Wolossébougou

Other trials in Mali

About this study

Official title: Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Malaria Transmission Season in Healthy African Adult Women of Childbearing Potential in Mali

Background:

Malaria is a disease spread by mosquitos. Pregnant women are highly susceptible to malaria. This can lead to poor health outcomes for pregnant women and their babies. Researchers want to test a malaria vaccine in women of child bearing potential (WOCBP) and pregnant women. This has not been done before.

Read more

Objective:

To assess the safety and tolerability of PfSPZ vaccine in healthy Malian WOCBP.

Eligibility:

Healthy women ages 18 38 who live in Ouelessebougou, Mali, and surrounding villages

Design:

Participants will be screened with:

  • Physical exam
  • Medical history
  • Blood, urine, and heart tests
  • Multiple-choice test about malaria

Participants will get 3 injections by needle into a vein of the study vaccine or a placebo. All 3 will be within 1 month. They will not know whether they receive the vaccine or placebo.

Participants will receive treatment to prevent malaria. This will be about 2 weeks before the first and third injections.

After the third injection, participants will be followed for about 1 year. They will be tested to see if the vaccine is safe and protects against malaria infection. They will have blood tests.

If participants get a rash or injection site reaction, photos of the site may be taken.

Any women who become pregnant during the trial will be followed through the end of pregnancy. Babies and their mothers will be followed through the first year of life

Read the detailed description

Pregnant women are highly susceptible to Plasmodium falciparum malaria, leading to substantial maternal, perinatal, and infant mortality. While malaria vaccine development has made significant progress in recent years, no trials of malaria vaccines have ever been conducted in only women of child bearing potential (WOCBP) or in pregnant women.

PfSPZ Vaccine (Sanaria, Inc) is an advanced malaria candidate being developed for use in

pregnant women, owing in part to its highly favorable safety profile. The vaccine is comprised of aseptic, metabolically active, non-replicating, purified, cryopreserved P. falciparum sporozoites. In multiple double-blind, placebo-controlled trials, there have been no differences in adverse events between vaccinees versus controls. PfSPZ Vaccine induces immune responses to the sporozoite and liver stages of parasite development in the human host and prevents progression to blood stage parasitemia as well as averting disease sequelae; a compelling rationale to test PfSPZ Vaccine for its benefits in this proposed population.

Sanaria has already achieved vaccine efficacy against homologous and heterogenous parasite populations in endemic areas following three doses of PfSPZ Vaccine in several studies with 9.0x10^5 and 1.8x10^6 PfSPZ Vaccine and has explored accelerated regimens, such as 1, 8, 29 days. Accelerated PfSPZ Vaccine regimens such as this could induce protection earlier in pregnancy, minimizing the period at risk and improving pregnancy outcomes over the control group.

Given this, the Malaria Research and Training Center, the Laboratory of Malaria Immunology

and Vaccinology National Institute of Allergy and Infectious Diseases, and Sanaria, Inc. propose to initiate testing of the day 1, 8, and 29 dosing regimen of PfSPZ Vaccine in WOCBP, and in subsequent studies, in pregnant women, using doses of 9.0x10^5 and 1.8x10^6 PfSPZ Vaccine. This will be the first step in a clinical development plan for PfSPZ Vaccine in WOCBP and pregnant women: 1) safety and efficacy studies in non-pregnant WOCBP (this trial), 2) studies of the safety and efficacy of a primary immunization series in all trimesters, and 3) studies to evaluate the safety and efficacy of boosting during pregnancy.

A pregnancy registry study (#17-I-N018) has been ongoing in Mali since 2017 to gain

background data on maternal/fetal outcomes in the target population in anticipation of this study. Women who become pregnant during the course of this study, and their offspring, will be followed for maternal clinical outcomes and malaria infection.

Conditions
Malaria
Being tested
PfSPZ Vaccine, Normal Saline
Keywords
Pregnancy, Tolerability, Immune, Response, Vaccination
Medical subject headings
Malaria

What participants receive

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

  • PfSPZ VaccineBiological

    PfSPZ vaccine is comprised of aseptic, metabolically active, non-replicating, purified, cryopreserved P. falciparum sporozoites.

  • Normal SalineOther

    Sterile isotonic (0.9%) normal saline is a clear liquid, making it indistinguishable from the study product when drawn up into a syringe; and will be used as a placebo, rather than a comparator vaccine

Study groups in NCT03989102
Study groupRoleWhat they receive
Arm 1ExperimentalArm 1: (n= 100) will receive 3 doses of PfSPZ Vaccine (9 x10(5)) via direct venous inoculation (DVI) at 1, 8, 29 days.
Receives: Biological: PfSPZ Vaccine
Arm 2ExperimentalArm 2: (n= 100) will receive 3 doses of PfSPZ Vaccine (1.8 x10(6)) via DVI at 1, 8, 29 days.
Receives: Biological: PfSPZ Vaccine
Arm 3Placebo comparatorArm 3: (n=100): will receive 3 doses of normal saline (placebo) injection via DVI at 1, 8, 29 days.
Receives: Other: Normal Saline

What is being measured

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

  1. Number of Participants With Adverse Events Within 7 Days After Each Vaccine Administration

    Assess safety and tolerability of PfSPZ Vaccine primary series in healthy Malian women of child-bearing potential (WOCBP) when given at 1, 8, 29 days at two doses (9 x10^5; 1.8 x10^6).

    Measured: 7 days after each vaccination at days 1, 8, and 29

Timeline

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

  1. First posted18 Jun 2019
  2. Study start3 Jul 2019
  3. Primary completion5 Apr 2022
  4. Study completion17 Mar 2023

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 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
324 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03989102
Sponsor's protocol ID
999919113
Other IDs
19-I-N113
Status last verified
May 2022
First submitted
14 Jun 2019
Last updated
19 Mar 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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, 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.

    PubMed 28216244

  • 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

  • Sirima SB, Ouedraogo A, Tiono AB, Kabore JM, Bougouma EC, Ouattara MS, Kargougou D, Diarra A, Henry N, Ouedraogo IN, Billingsley PF, Manoj A, Abebe Y, Kc N, Ruben A, Richie TL, James ER, Joshi S, Shrestha B, Strauss K, Lyke KE, Plowe CV, Potter GE, Cox C, Jones W, Sim BKL, Hoffman SL, Laurens MB. A randomized controlled trial showing safety and efficacy of a whole sporozoite vaccine against endemic malaria. Sci Transl Med. 2022 Dec 7;14(674):eabj3776. doi: 10.1126/scitranslmed.abj3776. Epub 2022 Dec 7.

    PubMed 36475905

  • Mordmuller B, Sulyok Z, Sulyok M, Molnar Z, Lalremruata A, Calle CL, Bayon PG, Esen M, Gmeiner M, Held J, Heimann HL, Woldearegai TG, Ibanez J, Flugge J, Fendel R, Kreidenweiss A, Kc N, Murshedkar T, Chakravarty S, Riyahi P, Billingsley PF, Church LWP, Richie TL, Sim BKL, Hoffman SL, Kremsner PG. A PfSPZ vaccine immunization regimen equally protective against homologous and heterologous controlled human malaria infection. NPJ Vaccines. 2022 Aug 23;7(1):100. doi: 10.1038/s41541-022-00510-z.

    PubMed 35999221

  • 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

  • Diawara H, Healy SA, Mwakingwe-Omari A, Issiaka D, Diallo A, Traore S, Soumbounou IH, Gaoussou S, Zaidi I, Mahamar A, Attaher O, Fried M, Wylie BJ, Mohan R, Doan V, Doritchamou JYA, Dolo A, Morrison RD, Wang J, Hu Z, Rausch KM, Zeguime A, Murshedkar T, Kc N, Sim BKL, Billingsley PF, Richie TL, Hoffman SL, Dicko A, Duffy PE; PfSPZ Vaccine Study Team. Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials. Lancet Infect Dis. 2024 Dec;24(12):1366-1382. doi: 10.1016/S1473-3099(24)00360-8. Epub 2024 Aug 14.

    PubMed 39153490

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PfSPZ Vaccine and Normal Saline 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 7 inclusion and 23 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 19 Mar 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Adverse Events Within 7 Days After Each Vaccine Administration (time frame: 7 days after each vaccination at days 1, 8, and 29). 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 NCT03989102, which also lists 7 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 19 Mar 2024.

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