Clinical Trial: Ph 2B/3 Tafenoquine (TFQ) Study in Prevention of Vivax Relapse

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary: Plasmodium vivax represents 50-80% of all malarial cases in Latin America and South East Asia. It is able to establish a dormant liver stage called the hypnozoite. Hypnozoite activation after initial infection can cause a relapse. Currently the only widely available drug is primaquine which requires administration over 14 days, resulting in poor compliance and treatment failure. Tafenoquine (an 8-aminoquinoline anti-malarial drug) has been shown to possess activity against all stages of the plasmodium life cycle, including the dormant stage in the liver. This is a multi-centre, double dummy, double blind, parallel group, randomized, active control study which is conducted in two parts. For both parts, subjects are treated with Chloroquine on days 1 to 3 (600mg, 600mg, and 300mg) to treat the blood stage vivax malaria. Part 1 will include at least 324 subjects and part 2 at least 600 subjects. Part 1 has 6 treatment arms, arms 1 to 4 contain different doses of Tafenoquine (50mg, 100mg, 300mg, and 600mg) dosed on day 1 or 2, arm 5 contains primaquine (15mg) dosing over 14 days (days 2-15 (15mg)) and arm 6 contains chloroquine only. The aim of this is to find a dose of Tafenoquine which meets the defined dose criteria. Based on Part 1 efficacy and safety, a single Tafenoquine dose (300 mg) will be studied in the pivotal Part 2. Part 2 contains 3 treatment arms one with the selected Tafenoquine dose (300 mg), the second arm will be 15mg Primaquine which will again be dosed over 14 days and the final arm contains chloroquine only dosed days 1-3 (600mg, 600mg, 300mg). Therefore as with Part 1, in Part 2 all subjects will receive Chloroquine. The aim of Part 2 is to investigate the safety and efficacy of the selected Tafenoquine/Chloroquine dose in the treatment and radical cure of Plasmodium vivax malaria. In addition to the Primary and Secondary endpoints stated below we will also be collecting; other efficacy endpoints (gametocyte clearance time, Recrudescence defined a
Sponsor: GlaxoSmithKline

Current Primary Outcome:

• Relapse Efficacy [ Time Frame: 6 months post dosing (180 days) ]
  Subjects for whom initial clearance of parasitaemia is confirmed (parasite numbers fall below the limit of detection in thick blood smear and remain undetectable at the second smear collected 6-12 hours later) and who do not present with Plasmodium vivax asexual stage parasites within six months will be considered treatment success.
• Relapse-free efficacy (Part 2) [ Time Frame: 6 months post dosing (180 days) ]
  Subjects for whom initial clearance of parasitaemia is confirmed (parasite numbers fall below the limit of detection in thick blood smear and remain undetectable at the second smear collected 6-12 hours later) and who do not present with Plasmodium vivax asexual stage parasites at any point in the study, and have a negative P. vivax smear within the acceptable time window for the six month assessment will be considered treatment success.

Original Primary Outcome: Relaspse Efficacy [ Time Frame: 6 months post dosing (180 days) ]

Current Secondary Outcome:

• Relapse Efficacy (Part 1) [ Time Frame: 4 months post dosing ]
  First confirmed presence of Plasmodium vivax asexual stage parasites after clearance of initial parasitemia following treatment.
• Time to relapse [ Time Frame: Within 180 days post dosing ]
  Time from initial parasite clearance to time of relaspe
• Parasite clearance time [ Time Frame: From first dose until Day 180 ]
  Time needed to clear asexual parasites from blood, parasites fall below limit of detection in thick blood smear and remains undetectable for at least 48 hours.
• Fever clearance time [ Time Frame: From first dose until Day 180 ]
  Time from first dose of treatment to time when body temperature falls to normal and remains normal for at least 48 hours.
• Healthcare Impact (Part 2) [ Time Frame: From first dose until Day 180 ]
  Health resource use (excluding clinic visits scheduled as part of the study).
• Relapse-free efficacy (Part 2) [ Time Frame: 4 months post dosing ]
  First confirmed presence of Plasmodium vivax asexual stage parasites after clearance of initial parasitemia following treatment.

Original Secondary Outcome:

• Relapse Efficacy [ Time Frame: 4 months post dosing ]
  First confirmed presence of Plasmodium vivax asexual stage parasites after clearance of initial parasitemia following treatment.
• Time to relapse [ Time Frame: Within 180 days post dosing ]
  Time from initial parasite clearance to time of relaspe
• Parasite clearance time [ Time Frame: From first dose until Day 180 ]
  Time needed to clear asexual parasites from blood, parasites fall below limit of detection in thick blood smear and remains undetectable for at least 48 hours.
• Fever clearance time [ Time Frame: From first dose until Day 180 ]
  Time from first dose of treatment to time when body temperatur falls to normal and remains normal for at least 48 hours.

Dates:
Date Received: June 16, 2011
Date Started: September 19, 2011
Date Completion:
Last Updated: April 25, 2017
Last Verified: April 2017