NCT04456634

Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of Ruxolitinib With Artemether-lumefantrine

Completed Phase 1 Results posted Last updated 9 July 2021

What this trial tests

Phase 1 trial testing 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux) in Malaria in 8 participants. Completed in 17 November 2020.

Timeline

10 September 2020

Primary endpoint
17 November 2020

17 November 2020

Quick facts

Lead sponsor	Medicines for Malaria Venture
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	single
Primary purpose	treatment
Enrollment	8
Start date	10 September 2020
Primary completion	17 November 2020
Estimated completion	17 November 2020
Sites	1 location across Australia

Drugs / interventions tested

• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux) — full drug profile →
• 20 mg/120 mg artemether-lumefantrine (AL) + Placebo

Conditions studied

• Malaria — all drugs for Malaria →

Sponsor

Medicines for Malaria Venture — full company profile →

Who can join

Adults 18 to 55, 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 Participant With Treatment-Related Adverse Events as Assessed by CTCAE V4.03, All of Observed and Self-reported AEs Affected, by Treatment Regimen. Primary · up to 28 days after AL+Rux and AL+placebo administration

Incidence, severity and relationship of observed and self-reported adverse events (AEs) were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.

Group	Value	95% CI
AL&RUX	6
AL& Placebo	2

Number of Participants With Changes of Systolic and Diastolic Blood Pressure Primary · up to 28 days after AL+Rux and AL+placebo administration

Safety signals, trends or significant differences in blood pressure between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.

Group	Value	95% CI
AL&RUX	2
AL& Placebo	0

Number of Participants With Changes in Heart Rate Primary · up to 28 days after AL+Rux and AL+placebo administration

Safety signals, trends or significant differences in heart rate ( beats / min)between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.

Group	Value	95% CI
AL&RUX	1
AL& Placebo	0

Number of Participants With ECG Changes Primary · up to 28 days after AL+Rux and AL+placebo administration

Safety signals, trends or significant differences in QT, QTcB and QTcF, QRS between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.

Group	Value	95% CI
AL&RUX	2
AL& Placebo	0

AUECt of pSTAT3 Inhibition Secondary · up to 28 days after AL+Rux and AL+placebo administration

Area under the effect curve (AUECt) of pSTAT3 inhibition levels

Group	Value	95% CI
AL&RUX	551	± 86.9
AL& Placebo	186	± 64.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AL&RUX

Serious: 0/6 (0%)

Deaths: 0/6

AL& Placebo

Serious: 0/2 (0%)

Deaths: 0/2

Other adverse events (6 terms — click to expand)

Reaction	System	AL&RUX	AL& Placebo
Headache	Nervous system disorders	—	—
Muscular back pain	Musculoskeletal and connective tissue disorders	—	—
Fatigue	General disorders	—	—
Vessel puncture site bruise	General disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—

Data from ClinicalTrials.gov NCT04456634 adverse events section.

Sponsor's own description

Phase 1, single -center study in 2 parts. The study designs for each part are well established for first-in-human studies and are appropriate to assess safety, tolerability and preliminary pharmacokinetics\& pharmacodynamics.

Publications & conference data

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

1. 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
2. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Coadministered Ruxolitinib and Artemether-Lumefantrine in Healthy Adults.
   Chughlay MF, Barnes KI, El Gaaloul M, Abla N, et al · · 2022 · cited 11× · PMID 34694880 · DOI 10.1128/aac.01584-21