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NCT03952650

Sanaria PfSPZ Challenge With Pyrimethamine or Chloroquine Chemoprophylaxis Vaccination (PfSPZ-CVac Approach): A Randomized Double Blind Placebo Controlled Phase I/II Trial to Determine Safety and Protective Efficacy Against Natural Plasmodium Falcipa...

Completed Phase 1, PHASE2 Results posted Last updated 12 July 2022
What this trial tests

Phase 1, PHASE2 trial testing Chloroquine Phosphate in Malaria in 252 participants. Completed in 10 February 2021.

Timeline
23 May 2019
Primary endpoint
10 February 2021
10 February 2021

Quick facts

Lead sponsorNational Institute of Allergy and Infectious Diseases (NIAID)
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingdouble
Primary purposeother
Enrollment252
Start date23 May 2019
Primary completion10 February 2021
Estimated completion10 February 2021
Sites1 location across Mali

Drugs / interventions tested

Conditions studied

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 18 to 50, any sex, with Malaria. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Positive Sensitive Blood Smear (sBS) Primary · 7 -12 days post-inoculation

Count of participants with positive sensitive blood smear (sBS) occurring after PfSPZ-CVac immunization starting on day 7 post DVI. Only pilot phase arms (Arms 1a, 2a) were analyzed for this outcome measure. Arms 5a and 6a were not performed, as no patent parasitemia was observed in either Arms 1a or 2a, per the protocol.

GroupValue95% CI
1a - Pilot/Safety: Dosing Interval on Days: 10
2a - Pilot/Safety: Dosing Interval on Days: 10
Number of Participants With Local and Systemic Grade 3 Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · From day of inoculation to 14 days post-inoculation

Count of participants with local and systemic grade 3 signs or symptoms lasting more than 48 hours despite adequate management and serious adverse events (SAEs) occurring after PfSPZ-CVac DVI. Only arm 3a was analyzed for this outcome measure, per the protocol objectives.

GroupValue95% CI
3a - Pilot/Safety: Dosing Interval on Days: 10
Number of Participants With Local and Systemic Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · For the main phase: from the day of inoculation to approximately 6 months post-3rd inoculation. For the booster phase: from the time of inoculation to approximately 6 months post-booster inoculation

Count of participants with local and systemic adverse events (AEs) and serious adverse events (SAEs) occurring after PfSPZ-CVac immunization. This outcome measure applies to main phase arms 1b, 2b, 4a, and 4b. Arms 5b and 6b were not performed as patent parasitemia with the higher dose of PfSPZ was not observed in the pilot phase (Arms 1a, 2a).

GroupValue95% CI
1b - Safety/Efficacy: Dosing Interval on Days: 1, 29, 5788
2b - Safety/Efficacy: Dosing Interval on Days: 1, 29, 5759
4a - Safety Comparator: Dosing Interval on Days: 1, 29, 5751
4b - Safety Comparator: Dosing Interval on Days: 1, 29, 5736

Adverse events — posted to ClinicalTrials.gov

Time frame: One month for pilot phase; eight months for main phase; seven months for booster phase. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1a - Pilot/Safety: Dosing Interval on Days: 1
Serious: 0/4 (0%)
Deaths: 0/4
1b - Safety/Efficacy: Dosing Interval on Days: 1, 29, 57
Serious: 1/90 (1%)
Deaths: 1/90
2a - Pilot/Safety: Dosing Interval on Days: 1
Serious: 0/4 (0%)
Deaths: 0/4
2b - Safety/Efficacy: Dosing Interval on Days: 1, 29, 57
Serious: 0/60 (0%)
Deaths: 0/60
3a - Pilot/Safety: Dosing Interval on Days: 1
Serious: 0/4 (0%)
Deaths: 0/4
4a - Safety Comparator: Dosing Interval on Days: 1, 29, 57
Serious: 1/54 (2%)
Deaths: 0/54
4b - Safety Comparator: Dosing Interval on Days: 1, 29, 57
Serious: 0/36 (0%)
Deaths: 0/36

Serious adverse events (2 terms)

ReactionSystem1a - Pilot/Safety: Dosing …1b - Safety/Efficacy: Dosi…2a - Pilot/Safety: Dosing …2b - Safety/Efficacy: Dosi…3a - Pilot/Safety: Dosing …4a - Safety Comparator: Do…4b - Safety Comparator: Do…
Gun shot woundInjury, poisoning and procedural complications
VolvulusGastrointestinal disorders
Other adverse events (83 terms — click to expand)

ReactionSystem1a - Pilot/Safety: Dosing …1b - Safety/Efficacy: Dosi…2a - Pilot/Safety: Dosing …2b - Safety/Efficacy: Dosi…3a - Pilot/Safety: Dosing …4a - Safety Comparator: Do…4b - Safety Comparator: Do…
RhinitisInfections and infestations
LeukopeniaBlood and lymphatic system disorders
Blood creatinine increasedInvestigations
NeutropeniaBlood and lymphatic system disorders
MalariaInfections and infestations
HeadacheNervous system disorders
Dental cariesGastrointestinal disorders
ConjunctivitisEye disorders
WoundInjury, poisoning and procedural complications
GastritisGastrointestinal disorders
PainGeneral disorders
SinobronchitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
BronchitisInfections and infestations
InfluenzaInfections and infestations
GastroenteritisInfections and infestations
Genital infectionInfections and infestations
Urinary tract infectionInfections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Alanine aminotransferase increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
ParonychiaInfections and infestations
PyrexiaGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Ear infectionInfections and infestations
Food poisoningGastrointestinal disorders
HypertensionVascular disorders
Injection site painGeneral disorders
InjuryInjury, poisoning and procedural complications
Limb injuryInjury, poisoning and procedural complications
NauseaGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Typhoid feverInfections and infestations
Arthropod stingInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
DermatosisSkin and subcutaneous tissue disorders

Most-reported serious reactions: Gun shot wound, Volvulus.

Data from ClinicalTrials.gov NCT03952650 adverse events section.

Sponsor's own description

Background: Malaria remains a major global health problem. Malaria is spread by the bite of mosquitos. Africa is the region of the world where most people get malaria. Sanaria PfSPZ Challenge is a malaria vaccine. Researchers want to see if the vaccine combined with partner drugs can help protect against malaria. Objective: To test if injections with 3 monthly doses of Sanaria PfSPZ Challenge, combined with either pyrimethamine (PYR) or chloroquine as a partner drug, is safe, tolerable, and effective. Eligibility: Healthy people ages 18-50 years who live in Bancoumana, Mali, or nearby Design: Participants will be screened with the Malaria Comprehension Exam to check their understanding of the study. They will have a medical history. They will have a physical exam. They will have blood tests, urine tests, and heart tests. Participants will join either the pilot study or the main study. Participants will be assigned to groups. Depending on their group, they will get at least one injection of either a placebo or the vaccine. They may have up to 3 vaccines, 4 weeks apart. The injection will be into a vein with a needle. Participants will also take pyrimethamine or chloroquine by mouth. They will also take standard doses of antimalarial drugs by mouth. Participants will have blood tests throughout the study. Participants may develop a rash or injection site reaction. If this happens, photos of the site may be taken. Participants will be observed for infection for many days after the injections.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity.
    Mwakingwe-Omari A, Healy SA, Lane J, Cook DM, et al · · 2021 · cited 95× · PMID 34194041 · DOI 10.1038/s41586-021-03684-z
  2. Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults.
    Jongo SA, Urbano V, Church LWP, Olotu A, et al · · 2021 · cited 55× · PMID 33205741 · DOI 10.4269/ajtmh.20-0435
  3. Sporozoite immunization: innovative translational science to support the fight against malaria.
    Richie TL, Church LWP, Murshedkar T, Billingsley PF, et al · · 2023 · cited 44× · PMID 37571809 · DOI 10.1080/14760584.2023.2245890
  4. Malaria in 2022: Increasing challenges, cautious optimism.
    Jagannathan P, Kakuru A. · · 2022 · cited 39× · PMID 35562368 · DOI 10.1038/s41467-022-30133-w
  5. Rapidly Increasing Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence and Limited Clinical Disease in 3 Malian Communities: A Prospective Cohort Study.
    Sagara I, Woodford J, Kone M, Assadou MH, et al · · 2022 · cited 38× · PMID 34185847 · DOI 10.1093/cid/ciab589
  6. Severe Acute Respiratory Syndrome Coronavirus 2 Seroassay Performance and Optimization in a Population With High Background Reactivity in Mali.
    Woodford J, Sagara I, Dicko A, Zeguime A, et al · · 2021 · cited 35× · PMID 34612499 · DOI 10.1093/infdis/jiab498
  7. Novel malaria vaccines.
    Laurens MB. · · 2021 · cited 15× · PMID 34347570 · DOI 10.1080/21645515.2021.1947762
  8. Malaria therapeutics: are we close enough?
    Tripathi H, Bhalerao P, Singh S, Arya H, et al · · 2023 · cited 12× · PMID 37060004 · DOI 10.1186/s13071-023-05755-8

Verify or expand the search:

Other trials of Chloroquine Phosphate

Trials testing the same drug.

Other recruiting trials for Malaria

Currently open trials in the same condition.

Other National Institute of Allergy and Infectious Diseases (NIAID) trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing