The study aims to provide evidence of retinal safety to support the use of tafenoquine as a potential single dose radical cure treatment for patients with Plasmodium vivax (P. vivax) malaria (i.e., co-administration of a schizonticidal drug with TQ). The study will be conducted as a single masked, randomized, placebo-controlled, parallel group design. It will assess retinal changes from baseline using spectral domain optical coherence tomography (OCT) and fundus auto fluorescence (FAF) at Month 3 (90 days) post-dose in adult healthy volunteers (participants). A placebo control group will be used to compare the results in the TQ group. Interim analysis will be conducted after completing 100 out of 300 participants in TQ group and 50 out of 150 participants in matched placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
486
Tablet contains TQ as tafenoquine succinate. The 2 tablets (2 tablets of 150mg) of dark pink, capsule-shaped, film coated will be administered orally with 240ml of water.
It is the matched Placebo tablet. The 2 tablets (2 tablets of 150mg) of dark pink, capsule-shaped, film coated will be administered orally with 240ml of water.
GSK Investigational Site
Glendale, California, United States
GSK Investigational Site
Overland Park, Kansas, United States
GSK Investigational Site
Baltimore, Maryland, United States
Proportion of participants in the TQ group having retinal changes from Baseline in Central subfield thickness and Central retinal lesion thickness
The change from baseline will be assessed as a binomial output as, Yes or No. Spectral domain OCT (SD-OCT) images/scan will be obtained. For Central subfield thickness and Central retinal lesion thickness, change from baseline of at least 40 microns (µ) will be consider 'Yes'. Central Retinal Lesion Thickness is defined as the distance between the inner limiting membrane of the retina and the inner border of the choriocapillaris measured in the central 1millimeter (mm) of the centre scan
Time frame: Baseline and Day 90(follow-up)
Proportion of participants in the TQ group having retinal changes from Baseline in Total macular volume
The change from baseline will be assessed as a binomial output as, Yes or No. SD-OCT images/scan will be obtained. Total Macular Volume, change from baseline of 10% will be considered 'Yes'
Time frame: Baseline and Day 90(follow-up)
Proportion of participants in the TQ group having retinal changes from Baseline in Ellipsoid zone disruption
The change from baseline will be assessed as a binomial output as, Yes or No. SD-OCT images/scan will be obtained. Ellipsoid zone disruption will be assessed by manual reading
Time frame: Baseline and Day 90(follow-up)
Proportion of participants in the TQ group having retinal changes from Baseline in abnormal auto-fluorescence patterns
The change from baseline will be assessed as a binomial output as, Yes or No. SD-OCT images/scan will be obtained. Abnormal auto-fluorescence will be assessed by FAF by manual reading
Time frame: Baseline and Day 90(follow-up)
Mean change from baseline in OCT parameter like central retinal thickness as a safety measure
SD-OCT images/scan will be obtained. Central retinal thickness is the thickness at the centre point of the macula
Time frame: Baseline and Day 90(follow-up)
Mean change from baseline in OCT parameter like central subfield thickness as a safety measure.
SD-OCT images/scan will be obtained. Central subfield thickness measures thickness from top of Internal limiting membrane (ILM) to bottom of Retinal pigment epithelium (RPE).
Time frame: Baseline and Day 90(follow-up)
Mean change from baseline in OCT parameter like central retinal lesion thickness as a safety measure.
SD-OCT images/scan will be obtained. Central retinal lesion thickness measures a greatest linear thickness from ILM to inner border of choriocapillaris
Time frame: Baseline and Day 90(follow-up)
Mean change from baseline in OCT parameters;. Total macular volume as a safety measure.
SD-OCT images/scan will be obtained. Total macular volume describes the overall thickness of retina from top of ILM to bottom of RPE as a volume measurement.
Time frame: Baseline and Day 90(follow-up)
Mean change from baseline in OCT parameters ;. Ellipsoid zone disruption as a safety measure.
SD-OCT images/scan will be obtained. Ellipsoid zone disruption will measure zones of absent or irregular ellipsoid layer.
Time frame: Baseline and Day 90(follow-up)
Changes from baseline in the status of the outer retina/photoreceptor complex as a safety measure.
SD-OCT images/scan will be obtained.
Time frame: Baseline and Day 90(follow-up)
Proportion of participants with abnormal changes from baseline observed on FAF as a safety measure.
FAF images will be obtained. Qualitative assessment will be done to check for any abnormal patterns of auto-fluorescence in the macular region that may be indicative of disease of the retinal pigment epithelium.
Time frame: Baseline and Day 90(follow-up)
Mean change from baseline in best corrected visual acuity (BCVA) as a safety measure of TQ in comparison to placebo.
BCVA will be measured by a trained examiner
Time frame: Baseline and Day 90(follow-up)
Proportion of participants with vortex keratopathy from the slit lamp examination as a safety measure of TQ in comparison to placebo.
Vortex keratopathy (corneal deposits) will be confirmed by slit lamp examination. Anterior and posterior segment evaluation will be done.
Time frame: Baseline and Day 90(follow-up)
Number of participants with of adverse events as a safety measure
An AE is any untoward medical occurrence in a participant or clinical investigation temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Time frame: 90 days
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