Phase 1
N=6
Pyronaridine in Healthy Adult Participants Infected With Blood Stage Malaria
Malaria,Falciparum · Malaria · Malaria Recrudescence · Parasitemia · Protozoan Infections
Bottom Line
View on ClinicalTrials.gov: NCT05287893 ↗Enrolled (actual)
6
Serious AEs
0.0%
Results posted
Apr 2025
Primary outcome: Primary: Emax — 0.201 Maximum clearance rate (1/hour)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Pyronaridine (Drug); P. falciparum IBSM infection (Biological)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Medicines for Malaria Venture
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Emax |
0.201 | — |
| PRIMARY EC50 |
0.00575 | — |
| PRIMARY Hill Coefficient |
6.62 | — |
| PRIMARY Minimum Inhibitory Concentration (MIC) |
5.5 | — |
| PRIMARY Minimal Parasiticidal Concentration (MPC90) |
8 | — |
| PRIMARY Parasite Reduction Ratio in 48 h (log10PRR48) |
2.58; 2.53; 2.85 | — |
Summary
This is an open-label, adaptive study that will utilise the P. falciparum induced blood stage malaria (IBSM) model to characterise the pharmacokinetic/pharmacodynamic (PK/PD) profile of pyronaridine. Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. Following a screening period of up to 28 days, cohorts of up to 6 healthy participants will be enrolled. Each participant will be inoculated intravenously on Day 0 with P. falciparum infected erythrocytes. Participants will be followed up daily on Days 1 to 3, and will attend the clinical unit once on Days 4, 5, 6 and 7 for clinical evaluation and blood sampling. Participants will be admitted to the clinical trial unit on Day 8 for a single oral dose of pyronaridine.
Different doses of pyronaridine will be administered across and within cohorts. Participants will be randomised to a dose group on the day of dosing. The highest dose of pyronaridine administered will be no more than 720 mg; the lowest dose administered will be no less than 180 mg.
Each subsequent cohort will be composed of up to 3 dose groups. The Safety Data Review Team (SDRT) will review all available safety and tolerability data from the previous cohort/s prior to inoculation of the next cohort.
Participants will be confined in the clinical unit for at least 96 h (Days 8 - 12) to monitor the safety and tolerability of pyronaridine dosing. Upon discharge from the clinical unit participants will be monitored on an outpatient basis up to Day 50±2. Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2 or earlier.
Eligibility Criteria
Inclusion Criteria
Demography
- Male or female (non-pregnant, non-lactating) aged 18 to 55 years inclusive who will be contactable and available for the duration of the trial and up to two weeks following the EOS visit.
- Total body weight greater than or equal to 50 kg, and a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive). BMI is an estimate of body weight adjusted for height. It is calculated by dividing the weight in kilograms by the square of the height in metres.
Health status
- Certified as healthy by a comprehensive clinical assessment (detailed medical history and full physical examination).
- Vital signs at screening (measured after 5 min in the supine position):
- Systolic blood pressure (SBP) - 90-140 mmHg,
- Diastolic blood pressure (DBP) - 40-90 mmHg,
- Heart rate (HR) 40-100 bpm.
- At Screening and pre-inoculation with the malaria challenge agent: normal standard mean of triplicate 12-lead electrocardiogram (ECG) parameters after 5 minutes resting in supine position in the following ranges:
- QTcF ≤450 msec (male participants); QTcF ≤470 msec (female participants);
- QRS 50-120 msec
- PR interval ≤ 210 msec for both males and females, and
- Normal ECG tracing unless the PI or delegate considers an ECG tracing abnormality to be not clinically relevant.
- Women of childbearing potential (WOCBP) who anticipate being sexually active with a male during the trial must agree to the use of a highly effective method of birth control (see below) combined with a barrier contraceptive from the screening visit until 100 days after the last dose of pyronaridine (covering a full menstrual cycle of 30 days starting after 5 half-lives of last dose pyronaridine) and have a negative result on urine pregnancy test performed before inoculation with the malaria challenge agent.
Note:
a. Highly effective birth control methods include: combined (oestrogen and progestogen containing) oral/intravaginal/transdermal/implantable hormonal contraception associated with inhibition of ovulation, progestogen-only oral/injectable/implantable hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, or sexual abstinence or same sex relationship.
b. Female participants who are abstinent (from penile-vaginal intercourse) must agree to start a double method if they start a sexual relationship with a male during the study. Female participants must not be planning in vitro fertilisation within the required contraception period.
- Women of non-childbearing potential (WONCBP) are defined as:
- Natural (spontaneous) post-menopausal defined as being amenorrhoeic for at least 12 months without an alternative medical cause with a screening follicle stimulating hormone level (FSH) >25 IU/L (or at the local laboratory levels for post-menopause)
- Premenopausal with irreversible surgical sterilization by hysterectomy and/or bilateral oophorectomy or salpingectomy at least 6 months before screening (as determined by participant medical history) 8. Males who have, or may have, female sexual partners of child bearing potential during the course of the study must agree to use a double method of contraception including condom plus diaphragm, or condom plus intrauterine device, or condom plus stable oral/transdermal/injectable/implantable hormonal contraceptive by the female partner, from the time of informed consent through to 70 days (covering a spermatogenesis cycle) after pyronaridine administration. Abstinent males must agree to start a double method if they begin sexual relationship with a female during the study and up to 70 days after the last dose of pyronaridine. Males with female partners of child-bearing potential that are surgically sterile, or males who have undergone sterilisation and have had testing to confirm the success of the sterilisation, may also be included and will not be required to u
Data sourced from ClinicalTrials.gov (NCT05287893). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.