The goal of this Phase 2b study is to examine the safety and efficacy of the combination of SJ733, an investigational agent, and tafenoquine for the radical cure of uncomplicated P. vivax malaria monoinfection in adult participants and determine the contributions of SJ733 to the effect. SJ733 will be administered in a 1-, 2-, or 3-day treatment schedule in combination with a single dose of tafenoquine.
SJ733-2002 study is a blinded, randomized, placebo- and active comparator-controlled study to examine the safety and efficacy of combining 1, 2, or 3 sequential daily doses of SJ733 with a single dose of TQ given on Day 1 for the radical cure of uncomplicated P. vivax malaria. This study will also establish the role of SJ733 in driving blood stage and liver stage parasite killing and any pharmacological interactions with Tafenoquine (TQ). Hence, this study includes placebo controlled SJ733 and Chloroquine (CQ) monotherapy arms. The six arms in this study will be run simultaneously and participants randomized with a 1:1:1:1:1:1 ratio until all arms are filled. All participants will be monitored for 180 days, with parasitemia endpoints measured on Days 7, 14, 21, 28, 35, 42, 60, 120, and 180 to provide maximum comparability to historical studies. At all times during these studies any participants that develop symptomatic disease or detectable parasitemia will be rescued with local standard-of-care (according to national guidelines). Any participant who does not relapse during the study will be treated following the last day of the study with the same rescue therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
104
SJ733 combined with Tafenoquine Placebo
Chloroquine combined with Tafenoquine Placebo
Chloroquine combined with Tafenoquine
SJ733 (3-day schedule) combined with Tafenoquine
SJ733 (2-day schedule) combined with Tafenoquine
SJ733 (1 day schedule) combined with Tafenoquine
Asociación Civil Selva Amazónica (ACSA)
Iquitos, Loreto, Peru
Parasitological Recurrence Free survival (RFS)
Recurrence free survival (RFS), defined as non-relapses of P. vivax at 180 days given parasitemia clearance at 14 days.
Time frame: 14 - 180 days for each arm
Clinical Recurrence Free Survival
Absence of malaria-related clinical signs or symptoms over 180 days following confirmed parasitemia clearance at Day 14.
Time frame: 14 to 180 days for each arm
Percentage of patients with treatment related adverse events
Incidence, severity, drug-relatedness, and seriousness of adverse events
Time frame: 1 to 180 days for each arm
Percent of patients with clinically significant abnormal vital signs
Number of and seriousness of with clinically significant abnormal vital signs including changes from baseline
Time frame: 1 to 180 days for each arm
Percent of patients with a decrease in hemoglobin (HB) > 2 g/dL from baseline to an absolute value of <7 g/dL
Proportion of participants with a decrease in hemoglobin (Hb): \> 2 g/dL from baseline to an absolute value of \< 7 g/dL
Time frame: 1 to 180 days for each arm
Percent of patients with an Absolute Neutrophil Count < 1000/μL after baseline
Proportion of participants with an absolute neutrophil count \< 1,000/μL after baseline
Time frame: 1 to 180 days for each arm
Percent of patients with significant changes in ECG findings
Proportion of participants with significant changes in ECG findings, including heart rate, ECG intervals (PR, QTcB, QTcF), conduction changes or abnormalities
Time frame: 1 to 180 days for each arm
Percent of patients with clinically significant increases in venous methemoglobin levels
Proportion of participants with clinically significant increases in venous methemoglobin levels
Time frame: 1 to 180 days for each arm
Number of participants with signs and symptoms of uncomplicated P. vivax malaria infection
Proportion of participants with symptoms or physical examination signs related to uncomplicated P. vivax malaria (e.g., headache, nausea, fatigue, fever auxiliary temperature, \>/= 37.5 C, chills/shivering/rigors, prostration, conjunctival jaundice, and respiratory distress)
Time frame: 180 days for each arm
Parasite clearance Time
Parasite Clearance Kinetics in participants with P. vivax malaria infection as measured by Microscopy
Time frame: 72 hours for each arm
Area Under the Plasma Concentration Time Curve (AUC)
AUC of SJ733, its primary metabolite, SJ506, and tafenoquine
Time frame: 180 days
Maximum Plasma Concentration (Cmax)
Cmax of SJ733, its primary metabolite, SJ506, and tafenoquine
Time frame: 180 days
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