Malaria, Vivax
Conditions
Keywords
Malaria, Retinal, Ophthalmic, Plasmodium. vivax, Tafenoquine, Pharmacodynamic
Brief summary
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.
Interventions
DRUGTafenoquine 150 mg
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.
DRUGMatched placebo 150mg
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.
Sponsors
Medicines for Malaria Venture
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 45 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, brief physical examination, and laboratory tests. * Participant values for haematology and chemistry within the normal range. A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight between \>=35 kilogram (kg) and =\<100kg * Male OR Female. Female participant is eligible to participate if she is not pregnant (as confirmed by a negative \[serum or urine, according to site standard\] human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy or Postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to site specific laboratory reference ranges for confirmatory levels). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from screening until completion of the Day 90 follow-up visit. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants in the TQ group having retinal changes from Baseline in Central subfield thickness and Central retinal lesion thickness | Baseline and Day 90(follow-up) | 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 |
| Proportion of participants in the TQ group having retinal changes from Baseline in Total macular volume | Baseline and Day 90(follow-up) | 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' |
| Proportion of participants in the TQ group having retinal changes from Baseline in Ellipsoid zone disruption | Baseline and Day 90(follow-up) | 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 |
| Proportion of participants in the TQ group having retinal changes from Baseline in abnormal auto-fluorescence patterns | Baseline and Day 90(follow-up) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in OCT parameters ;. Ellipsoid zone disruption as a safety measure. | Baseline and Day 90(follow-up) | SD-OCT images/scan will be obtained. Ellipsoid zone disruption will measure zones of absent or irregular ellipsoid layer. |
| Changes from baseline in the status of the outer retina/photoreceptor complex as a safety measure. | Baseline and Day 90(follow-up) | SD-OCT images/scan will be obtained. |
| Proportion of participants with abnormal changes from baseline observed on FAF as a safety measure. | Baseline and Day 90(follow-up) | 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. |
| Mean change from baseline in OCT parameter like central retinal thickness as a safety measure | Baseline and Day 90(follow-up) | SD-OCT images/scan will be obtained. Central retinal thickness is the thickness at the centre point of the macula |
| Proportion of participants with vortex keratopathy from the slit lamp examination as a safety measure of TQ in comparison to placebo. | Baseline and Day 90(follow-up) | Vortex keratopathy (corneal deposits) will be confirmed by slit lamp examination. Anterior and posterior segment evaluation will be done. |
| Number of participants with of adverse events as a safety measure | 90 days | 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 |
| Mean change from baseline in best corrected visual acuity (BCVA) as a safety measure of TQ in comparison to placebo. | Baseline and Day 90(follow-up) | BCVA will be measured by a trained examiner |
| Mean change from baseline in OCT parameter like central subfield thickness as a safety measure. | Baseline and Day 90(follow-up) | 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). |
| Mean change from baseline in OCT parameter like central retinal lesion thickness as a safety measure. | Baseline and Day 90(follow-up) | SD-OCT images/scan will be obtained. Central retinal lesion thickness measures a greatest linear thickness from ILM to inner border of choriocapillaris |
| Mean change from baseline in OCT parameters;. Total macular volume as a safety measure. | Baseline and Day 90(follow-up) | 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. |
Countries
United States
Outcome results
None listed