A Phase 2B Trial of the Combination of SJ733 and Tafenoquine for Radical Cure of P. Vivax Malaria in Comparison to Chloroquine-Tafenoquine
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Efficacy of the combination of SJ733 and tafenoquine for radical cure of P. vivax malaria.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor and CRO remain blinded (except the unblinded team members). Pharmacist at the site remains unblinded
入排标准
- 年龄范围
- 18 Years 至 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body weight between 45 kg and 90 kg inclusive.
- •Presence of mono-infection of P. vivax confirmed by: Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic temperature ≥ 38°C, or history of fever in the previous 24 hours (history of fever must be documented) and, Microscopically confirmed parasite infection: 1,000 to 40,000 asexual parasite count/µL blood
- •Written informed consent provided by participant, in accordance with local practice. If the participant is unable to write, witnessed consent is permitted according to local ethical considerations.
- •Ability to swallow oral medication.
- •Ability and willingness to participate and to comply with the study requirements.
- •Agreement to hospitalization for at least 72 hours and/or until malarial parasites are not detected by microscopy on 2 consecutive occasions.
- •Agreement to come back to the hospital on Days 4, 7, 14, 21, 28, 35, 42, 60, 120, and
- •A female participant meets eligibility in this study if she is non-pregnant, non-lactating and if she is of: non-childbearing potential defined as: post-menopausal (12 months of spontaneous amenorrhea or <6 months of spontaneous amenorrhea with serum FSH >40 mIU/mL), pre-menopausal and has had a hysterectomy, a bilateral oophorectomy (removal of the ovaries), or a bilateral tubal ligation with medical report verification, negative pregnancy test or, child-bearing potential, with a negative 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 75 days after stopping study treatment:
- •i. Use of oral, implantable, or injectable hormonal contraceptive, either combined or progestogen alone, used in conjunction with barrier method (condom or diaphragm).
- •ii. Use of an intrauterine device with a documented failure rate of <1% per year.
- •iii. Double barrier method consisting of condom and diaphragm. iv. Male partner who is sterile prior to the female participant's entry into the study and is the sole sexual partner for that female.
- •v. Complete abstinence from intercourse throughout the study and for a period of 75 days after stopping study treatment.
- •A male participant meets eligibility in this study if he meets one of the following conditions:
- •is sterile prior to participating in the study.
- •agrees to the use of a contraceptive method (such as a condom) through the administration of study treatment and for a period of 75 days after stopping study treatment.
- •agrees to complete abstinence from intercourse throughout the study and for a period of 75 days after stopping study treatment.
排除标准
- •Signs and symptoms of severe/complicated malaria according to the World Health Organization Criteria
- •Mixed Plasmodium infection or Plasmodium mono-infection with any Plasmodium species other than P. vivax.
- •Severe vomiting, defined as more than three times in the 24 hours prior to the planned first dose of drug, or severe diarrhea defined as 3 or more watery stools per day.
- •Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalized reference values).
- •The presence of a significant medical or psychiatric condition, or any other serious or chronic clinical condition requiring hospitalization, or any other condition that in the opinion of the investigator precludes participation in the study.
- •Female participants must not be lactating or pregnant as demonstrated by a negative serum point-of-care pregnancy test pre-dose (the result of the pre-dose assessment must be confirmed negative prior to dosing).
- •Employment under the direct supervision of the investigators or study staff.
- •Clinically significant alterations to hematologic or clinical chemistry parameters that in the opinion of the investigator precludes participation in the study, including:
- •AST/ALT > 3 x upper limit of normal range (ULN) and total bilirubin is normal.
- •AST/ALT > 2 x ULN and total bilirubin is >1 and <2 x ULN and conjugated bilirubin is > 2x ULN.
- •Serum creatinine levels > 2 x ULN
- •Uncorrected electrolyte abnormalities [> 3x ULN or LLN]
- •i. Potassium[hypokalemia] ii. Magnesium [hypomagnesemia] e. Hb level < 9 g/dL f. Platelet level < 50,000/mm3
- •Clinically significant alterations to cardiac function
- •Unstable angina with elevated serum cardiac biomarkers, ECG changes, etc.; those with NSTE-ACS, NSTEMI, STEMI, or definite acute coronary syndrome.
- •Congestive heart failure
- •Recent history of Myocardial Infarction
- •QT prolongation (>450 milliseconds (ms) in men and 460 ms in women)
- •Participation in a clinical study of another small investigational molecule within 30 days or investigational biologic within 90 days prior to study enrollment or planning to begin such participation during the study.
- •Received any antimalarial treatment (alone or in combination) in the past containing:
- •Tafenoquine within the previous 4 months
- •Piperaquine, mefloquine, naphthoquine or sulphadoxine / pyrimethamine within the previous 5 months
- •Amodiaquine or chloroquine within the previous 5 months
- •Any artemisinin (artesunate, artemether, arteether or dihydroartemisinin), quinine, halofantrine, lumefantrine and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 3 months.
- •Known history of hypersensitivity, allergic, or adverse reactions to SJ733, tafenoquine or other 8-aminoquinolines, or chloroquine or other 4-aminoquinolines.
- •Current use of prohibited concomitant medications (Appendix III)
- •Known neuropsychiatric disorders.
- •G6PD deficiency <70% normal enzyme activity.
- •Prohibited use of metoclopramide, antibiotics including fluoroquinolones
- •Positive HIV and/or Hepatitis B, C test results
研究组 & 干预措施
Arm 2- Chloroquine and Tafenoquine Placebo
Chloroquine (600 mg) for 2 consecutive days then Chloroquine (300 mg) for 1 day, combined with tafenoquine placebo on the first day
干预措施: CQ/TQ Placebo (Drug)
Arm 3 - Chloroquine and Tafenoquine
Chloroquine (600 mg) for 2 consecutive days then Chloroquine (300 mg) for 1 day, combined with tafenoquine (300 mg) once on the first day
干预措施: CQ/TQ (Drug)
Arm 4b - SJ733 for 2 days and Tafenoquine
SJ733 (600 mg) once a day for 2 consecutive days, followed by SJ733 placebo for 1 day, combined with tafenoquine (300 mg) once on the first day
干预措施: SJ733 (2-day ) /TQ (Drug)
Arm 4a -SJ733 for three days and Tafenoquine
SJ733 (600 mg) once a day for 3 consecutive days combined with tafenoquine (300 mg) once on the first day
干预措施: SJ733 (3-day)/TQ (Drug)
Arm1 - SJ733 600 mg for 3 days and Tafenoquine Placebo
SJ733 (600 mg) once a day for 3 consecutive days combined with tafenoquine placebo on the first day
干预措施: SJ733/TQ placebo (Drug)
Arm 4c - SJ733 for one day and Tafenoquine
SJ733 (600 mg) once, followed by SJ733 placebo for 2 days, combined with tafenoquine (300 mg) once on the first day
干预措施: SJ733(1-day)/TQ (Drug)
结局指标
主要结局
Efficacy of the combination of SJ733 and tafenoquine for radical cure of P. vivax malaria.
时间窗: 14 - 180 days
Parasitological and Clinical Recurrence Free survival with confirmed clearance at 14 days
Safety and Tolerability
时间窗: 1 to 180 days
Incidence, severity, drug-relatedness, and seriousness of adverse events
次要结局
- Effect of the combination of SJ733 and TQ on the pattern, severity, and duration of clinical signs and symptoms of P. vivax malaria infection(180 days)
- Parasite clearance kinetics in participants with P. vivax malaria infection(72 hours)
- Area Under the Plasma Concentration Time Curve (AUC)(180 days)
- Maximum Plasma Concentration (Cmax)(180 days)
研究者
R. Kiplin Guy
Principal Investigator
University of Kentucky