Last updated: 07/17/2024 15:22:30
Ph 2B/3 Tafenoquine (TFQ) study in prevention of vivax relapse
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A multi-centre, double-blind, randomised, parallel-group, active controlled study to evaluate the efficacy, safety and tolerability of tafenoquine (SB-252263, WR238605) in subjects with Plasmodium vivax malaria.
Trial description: The purpose of this two part study is to test the safety and efficacy of Tafenoquine (with Cholorquine) as a radical cure for Plasmodium vivax (P.vivax) malaria relative to the control Chloroquine.Part 1 aims to select an efficacious and well tolerated dose that can be co-administered with Chloroquine. Part 2 will investigate the safety and efficacy of the selected dose (300 mg tafenoquine) in the treatment and radical cure of Plasmodium Vivax Malaria.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Number of participants with recurrence-free efficacy at 6 months post dose
Timeframe: 6 months post dose
Secondary outcomes:
Number of participants with recurrence-free efficacy at 4 months post dose
Timeframe: 4 months post dose
Time to recurrence of P vivax malaria
Timeframe: Up to Day 180
Time to parasite clearance
Timeframe: Up to Day 180
Time to fever clearance
Timeframe: Up to Day 180
Number of participants with hemoglobin decline from Baseline over first 29 days
Timeframe: Baseline and up to Day 29
Number of participants with treatment emergent adverse events (TEAEs) potentially related to hemoglobin decrease
Timeframe: Up to Day 180
Number of participants who received blood transfusion
Timeframe: Up to Day 180
Number of participants with acute renal failure
Timeframe: Up to Day 180
Change from Baseline in percent methemoglobin
Timeframe: Baseline and up to Day 120
Number of participants with gastrointestinal disorders
Timeframe: Up to Day 180
Number of participants with keratopathy
Timeframe: Up to Day 180
Incidence of visual field abnormalities based on Best Corrected Visual Acuity Test Scores
Timeframe: Up to Day 180
Number of participants with retinal changes from Baseline
Timeframe: Baseline and up to Day 180
Number of participants with TEAEs and serious TEAEs
Timeframe: Up to Day 180
Number of participants with TEAEs by maximum intensity
Timeframe: Up to Day 180
Number of participants with hematology laboratory data outside the reference range
Timeframe: Up to Day 120
Number of participants with clinical chemistry laboratory data outside the reference range
Timeframe: Up to Day 120
Cost associated with recurrence episode of P vivax malaria
Timeframe: Up to Day 180
Cost incurred with purchase of medications associated with recurrence episode of malaria
Timeframe: Up to Day 180
Time lost by participants or care givers from normal occupation
Timeframe: Up to Day 180
Number of participants with action taken to treat recurrence episode of P vivax malaria
Timeframe: Up to Day 180
Oral clearance (CL/F) of TQ
Timeframe: Day 2, Day 8, Day 15, Day 29 and Day 60
Volume of distribution (Vc/F) of TQ
Timeframe: Day 2, Day 8, Day 15, Day 29 and Day 60
Interventions:
Drug: Chloroquine 600mg
Drug: Chloroquine 300mg
Drug: Tafenoquine 50mg
Drug: Tafenoquine 100mg
Drug: Tafenoquine 300mg
Drug: Tafenoquine 600mg
Drug: Primaquine 15mg
Drug: Chloroquine 600mg (Part 2 )
Drug: Chloroquine 300mg (Part 2 )
Drug: Tafenoquine 300mg (Part 2)
Drug: Primaquine 15mg (Part2 )
Enrollment:
851
Observational study model:
Not applicable
Primary completion date:
2016-18-11
Time perspective:
Not applicable
Clinical publications:
Llanos, Ronnatrai, Krudsood, Lacerda, Gupta, Kochar, Arthur, Kellam, Green, Ugwuegbulam, Carter, Kleim, Duparc, Moehrle.Efficacy, safety and tolerability of tafenoquine in subjects with P. vivax malaria.Lancet.2014;383:1049-58
Lacerda MVG, Llanos-Cuentas EA, Krudsood S, Chanthap L, Saunders DL, Mohammed R, Yilma D, Pereira D, Espino F, Mia R, Chuquiyauri R, Val F, Casapia M, Monteiro W, Brito M, Costa M, Buathong N, Noedl H, Diro E, Getie S, Mekonnen K, Abdissa A, Zeynudin A, Abebe C, Tada MS, Angus B, Duparc S, Kleim JP, Kellam LM, Rousell VM, Jones SW, Hardaker E, Mohamed K, Clover DD, Fletcher K, Breton, JJ, Ugwuegbulam CO, Green JA, Koh GCKW.EPC Recording: Single-dose Tafenoquine for Relapse Prevention in Plasmodium vivax Malaria.N Engl J Med.2019;380:215-28
DOI: 10.1056/NEJMoa1710775
PMID: 30650322
Medical condition
Malaria, Vivax
Product
tafenoquine
Collaborators
Medicines for Malaria Venture
Study date(s)
April 2014 to November 2016
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
16+ years
Accepts healthy volunteers
No
- Positive Giemsa smear for P. vivax
- Parasite density >100 and <200,000/μL
- Mixed malaria infections (e.g. identified by Giemsa-stained smear or rapid diagnostic test)
- Severe vivax malaria as defined by World Health Organisation criteria.
Inclusion and exclusion criteria
Inclusion criteria:
- Positive Giemsa smear for P. vivax
- Parasite density >100 and <200,000/μL
- ≥16 years
- A female is eligible if she is non-pregnant, nonlactating and if she is of:
- non-child bearing potential defined as: post-menopausal (12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone >40 mIU/mL), pre-menopausal and has had a hysterectomy or a bilateral oophorectomy (removal of the ovaries) or a bilateral tubal ligation with medical report verification, negative pregnancy test or,
- child-bearing potential, has a negative serum pregnancy test at screening, and agrees to comply with one of the following during the treatment stage of the study and for a period of 90 days after stopping study drug:
- Use of oral contraceptive, either combined or progestogen alone used in conjunction with double barrier method as defined below
- Use of an intrauterine device with a documented failure rate of <1% per year
- Use of depo provera injection (part 2)
- Double barrier method consisting of spermicide with either condom or diaphragm
- Male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female.
- Complete abstinence from intercourse for 2 weeks prior to administration of study drug, throughout the study and for a period of 90 days after stopping study drug.
- A signed and dated informed consent is obtained from the subject or the subject’s legal representative prior to screening. NB Assent is obtained from subjects <18 years, where applicable and written or oral witnessed consent has been obtained from parent or guardian.
- The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned.
- Willing to be hospitalized for 3 days and return to clinic for all follow-up visits including Day 180
- QTc <450 msec at screening, based on a single QTcF value at screening (part 1 only) or as an average of triplicate Electrocardiogram obtained over a brief recording period by machine or manual over-read if first is >450 msec.-
Exclusion criteria:
- Mixed malaria infections (e.g. identified by Giemsa-stained smear or rapid diagnostic test)
- Severe vivax malaria as defined by World Health Organisation criteria.
- Severe vomiting (no food or inability to take food during previous 8 hours)
- Screening haemoglobin concentration <7 g/dL.
- Glucose 6-phosphate dehydrogenase deficiency, assessed by a quantitative spectrophotometric phenotype assay: Part 1
- Males: Any subject with an enzyme level <70% of the site median value for Glucose 6-phosphate dehydrogenase normals will be excluded. Females: Those females with a screening Hb ≥ 10 g/dL will only be excluded if their enzyme level is <70% of the site median value for Glucose 6-Phosphate dehydrogenase normals. hose females with Hb ≥7 but < 10 g/dL will be excluded if an enzyme level is not > 90% of the site median value for Glucose 6-Phosphate dehydrogenase normals. Part 2
- Any subject with enzyme level <70% of the site median value for Glucose 6-phosphate dehydrogenase normals will be excluded
- Liver function test alanine transaminase >2x Upper Limit of Normal
- Any clinically significant concurrent illness (e.g. pneumonia, septicaemia), pre-existing conditions (e.g. renal disease, malignancy), conditions that may affect absorption of study medication (e.g. vomiting or severe diarrhea) or clinical signs and symptoms of severe cardiovascular disease (e.g. uncontrolled congestive heart failure or severe coronary artery disease). These abnormalities may be identified on the screening history and physical or laboratory examination.
- Subject has taken antimalarials (e.g. ACT, mefloquine, primaquine, chloroquine) or drugs with anti-malarial activity within the past 30 days by history.
- History of allergy to chloroquine, mefloquine, tafenoquine, primaquine or to any other 4- or 8-aminoquinolines.
- Any contraindications to chloroquine or primaquine administration including a history of porphyria, psoriasis or epilepsy (please refer to chloroquine and primaquine locally approved prescribing information).
- Subject who has previously received study medication for this protocol (all parts) or has received treatment with any other investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
- History of illicit drug abuse or heavy alcohol intake within 6 months of the study.
- Subjects who have taken or will likely require the use of medications from the prohibited medication list which include the following classes: Histamine-2 blockers and antacids.
- Drugs with haemolytic potential.
- Drugs known to prolong the QTc interval
Trial location(s)
Location
GSK Investigational Site
Porto Velho, Rondônia, Brazil, 76812-329
Status
Study Complete
Study documents
Protocol
Available language(s): English
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2016-18-11
Actual study completion date
2016-18-11
Plain language summaries
Summary of results in plain language
Available language(s): English
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
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