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NCT02867059: SJ733IBSMCS

SJ733 Induced Blood Stage Malaria Challenge Study

Completed Phase 1 Results posted Last updated 5 May 2020
What this trial tests

Phase 1 trial testing (+)-SJ000557733 in Plasmodium Falciparum Malaria in 17 participants. Completed in 22 December 2016.

Timeline
13 September 2016
Primary endpoint
22 December 2016
22 December 2016

Quick facts

Lead sponsorMedicines for Malaria Venture
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment17
Start date13 September 2016
Primary completion22 December 2016
Estimated completion22 December 2016
Sites2 locations across Australia

Drugs / interventions tested

Conditions studied

Sponsor

Medicines for Malaria Venture — full company profile →

Who can join

Adults 18 to 55, any sex, with Plasmodium Falciparum 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.

Activity of SJ733 Administered Orally on Clearance of P. Falciparum Blood Stage Parasites From the Blood in Healthy Subjects (Men and WNCBP) Primary · Until End of Study (Day 28±3)

The parasite reduction ratio (PRR) provides an estimate of the efficacy of an antimalarial treatment and is the ratio of the parasite density between admission and 48 h post antimalarial treatment. The primary efficacy variable is parasite reduction ratio (PRR) of parasites based on qPCR after administration of SJ733. The PRR was estimated using the slope of the optimal fit of the log-linear relationship of the parasitaemia decay. PRR was calculated for each subject using the retrospective 18S rRNA qPCR data. If the model fit was adequate for the subject (defined as overall model p-value \<0.

GroupValue95% CI
First Dose 150mg172103 – 286
Second Dose 600mg115515348 – 24944
Number of Participants With Adverse Events Primary · for up to 25th day post SJ733 treatment or longer as determind by the principal investigator

The safety and tolerability of SJ733 in healthy subjects (men and WNCBP) following infection with blood stage P. falciparum during the IBSM challenge study will be evaluated by observation of occurrence of adverse events.

GroupValue95% CI
First Dose 150mg7
Second Dose 600mg8

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

First Dose
Serious: 0/7 (0%)
Deaths:
Second Dose
Serious: 0/8 (0%)
Deaths:
Other adverse events (28 terms — click to expand)

ReactionSystemFirst DoseSecond Dose
ChillsGeneral disorders
MyalgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
PyrexiaGeneral disorders
TachycardiaCardiac disorders
MalaiseGeneral disorders
LymphopeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
LethargyNervous system disorders
HyperhidrosisSkin and subcutaneous tissue disorders
Abdominal DiscomfortGastrointestinal disorders
Lymphocyte count decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Eye IrritationEye disorders
HaematocheziaGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Puncture site erythemaGeneral disorders
Aspartate aminotransferase increasedInvestigations
Neutrophil count decreasedInvestigations
Urine output increasedInvestigations
White blood cell count decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
ParaesthesiaNervous system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT02867059 adverse events section.

Sponsor's own description

This is a single-centre, open-label, study using induced blood stage malaria (IBSM) infection to characterize the activity of (+)-SJ000557733 or SJ733 for short, against early Plasmodium falciparum blood stage infection. The study will be conducted in two cohorts (n=8 per cohort). The anticipated efficacious dose range is expected to be within a range of 125 to 600 mg. The dose used in the first cohort was determined on the basis of the safety and PK data generated in the FIM study (NCT02661373) currently ongoing in United States (US) and will be 150 mg. Depending on the pharmacodynamics data (effect of SJ733 on parasitaemia) obtained from this first cohort, the dose in Cohort 2 may be adjusted but will not exceed 600 mg. Based on the PK from all three cohort from the FIM study, the median estimated dose to obtain the target SJ733 AUC of 13,000 (ug hr/L) is 370 mg. The dose of cohort 2 (≤600mg) is intended to provide further concentration-response information in the human challenge model. For Cohort 2 only, a second dose of SJ733 may be administered at peak gametocytaemia to assess if SJ733 can reduce gametocytes and subsequent infectivity to mosquitoes (a washout of \~15 days post initial SJ733 treatment will be observed). Depending on the data obtained from the first two cohorts, there may be a subsequent cohort, with the investigated dose of SJ733 to be determined by the Sponsor and Principal Investigator (PI) and endorsed by the Safety Review Team. Should this third dose be investigated, a substantial amendment including preliminary data from the first two cohorts will be submitted to the HREC for approval.

Publications & conference data

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

  1. Drugs in Development for Malaria.
    Ashley EA, Phyo AP. · · 2018 · cited 123× · PMID 29802605 · DOI 10.1007/s40265-018-0911-9
  2. IgM in human immunity to <i>Plasmodium falciparum</i> malaria.
    Boyle MJ, Chan JA, Handayuni I, Reiling L, et al · · 2019 · cited 100× · PMID 31579826 · DOI 10.1126/sciadv.aax4489
  3. Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria.
    Vijay R, Guthmiller JJ, Sturtz AJ, Surette FA, et al · · 2020 · cited 94× · PMID 32424361 · DOI 10.1038/s41590-020-0678-5
  4. Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial.
    Gaur AH, McCarthy JS, Panetta JC, Dallas RH, et al · · 2020 · cited 55× · PMID 32275867 · DOI 10.1016/s1473-3099(19)30611-5
  5. Th2-like T Follicular Helper Cells Promote Functional Antibody Production during &lt;i&gt;Plasmodium falciparum&lt;/i&gt; Infection.
    Chan JA, Loughland JR, de Labastida Rivera F, SheelaNair A, et al · · 2020 · cited 52× · PMID 33377128 · DOI 10.1016/j.xcrm.2020.100157
  6. Liver Enzyme Elevations in <i>Plasmodium falciparum</i> Volunteer Infection Studies: Findings and Recommendations.
    Chughlay MF, Akakpo S, Odedra A, Csermak-Renner K, et al · · 2020 · cited 21× · PMID 32314694 · DOI 10.4269/ajtmh.19-0846
  7. Scoping Review of Antimalarial Drug Candidates in Phase I and II Drug Development.
    Abd-Rahman AN, Zaloumis S, McCarthy JS, Simpson JA, et al · · 2022 · cited 15× · PMID 34843390 · DOI 10.1128/aac.01659-21
  8. Positron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: A prospective cohort study.
    Woodford J, Gillman A, Jenvey P, Roberts J, et al · · 2021 · cited 11× · PMID 34038421 · DOI 10.1371/journal.pmed.1003567

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