Evaluating the safety, tolerability and anti-parasitic immunity boosting activity of ruxolitinib when co-administered with artemether-lumefantrine in adults with Plasmodium falciparum Induced Blood Stage Malaria
- Conditions
- MalariaInfection - Other infectious diseases
- Registration Number
- ACTRN12621000866808
- Lead Sponsor
- QIMR Berghofer Medical Research Institute
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 26
1. 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.
2. 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).
3. Certified as healthy by a comprehensive clinical assessment (detailed medical history and full physical examination).
4. 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.
5.At screening, continued eligibility (Day 85 plus or minus 7), pre-inoculation (first and second) and pre IMP dosing: QTcF less than or equal to 450 msec (male volunteers); QTcF less than or equal to 470 msec (female volunteers); PR interval less than or equal to 210 msec for both males and females.
1.Known hypersensitivity to ruxolitinib, artesunate or any of its derivatives, artemether, lumefantrine or other artemisinin derivatives, proguanil/atovaquone, primaquine, or 4-aminoquinolines.
2.Haematology, biochemistry or urinalysis results at screening or at the eligibility visit, or at the Day 85 plus or minus 7 continued eligibility visit that are outside of Sponsor-approved clinically acceptable laboratory ranges, or are considered clinically significant by the Investigator or their delegate.
3.Participation in any investigational product trial within the 12 weeks preceding IMP administration.
4.Symptomatic postural hypotension at screening (confirmed on two consecutive readings).
5.History or presence of diagnosed (by an allergist/immunologist) or treated (by a physician) food or known drug allergies (including but not limited to allergy to any of the antimalarial rescue medications), or any history of anaphylaxis or other severe allergic reactions including face, mouth, or throat swelling or any difficulty breathing.
6.History of convulsion (including drug or vaccine-induced episodes).
7.Presence of current or suspected serious chronic diseases
8.Individuals with history of schizophrenia, bipolar disorder psychoses, disorders requiring lithium, attempted or planned suicide, or any other severe (disabling) chronic psychiatric diagnosis including generalised anxiety disorder.
9.Presence of clinically significant infectious disease or fever (e.g., sublingual temperature greater than or equal to 38.5°C) within the five days prior to first and second inoculation.
10.Individual has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion (e.g. gastrectomy, diarrhoea).
11.Blood donation of any volume within one month before inclusion, or participation in any research trial involving blood sampling (more than 300 mL/unit of blood) within one month prior to IMP administration, or blood donation to Life Blood (Blood Service) or other blood bank during the 8 weeks prior to IMP administration.
12.Medical requirement for intravenous immunoglobulin or blood transfusions.
13.Any vaccination within the last 28 days.
14.Any history of malaria or participation in a previous malaria challenge trial or malaria vaccine trial.
15.Must not have had malaria exposure that is considered by the Investigator or delegate to be significant.
16.Cardiac/QT risk
17.Recent herpes zoster infection (within the previous 6-months) as determined by clinical history.
18.Positive result for M. tuberculosis infection by QuantiFERON-TB Gold assay.
19.Any recent (less than 6 weeks) or current systemic therapy with an antibiotic or drug with potential antimalarial activity
20.Has evidence of increased cardiovascular disease risk
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence, severity, and relationship as a composite outcome of observed and self-reported adverse events by treatment regimen. These may include headaches, diarrhoea, blood sampling catheter haemorrhage and neutropenia. <br>Safety assessments including physical examination, clinical laboratory analysis (biochemistry, haematology, and urinalysis), malaria clinical score recording, and electrocardiographs will be used for assessment.[Adverse event recording at all clinic visits and by phone contact from parasite inoculation (Day 0) to End of Study (EOS) at the following time-points: Days 0, 1, 2, 3 (phone contact), 9, 10, 11, 12 (clinical confinement), 14, 16, 19, 23 and 29 (out-patient visits), 30-85 plus/minus 7 (phone contact every 2 weeks), 85 plus/minus 7, 90 plus/minus 7, 91-93 plus/minus 7 (phone contact), 94-AL administration or 118 plus/minus 7 whichever comes first (out-patient visits), AL plus 3, AL plus 7 AL plus 20 and AL plus 28 (EOS).]
- Secondary Outcome Measures
Name Time Method