A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine (FQ) With Artefenomel (OZ439) in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 377
- 试验地点
- 12
- 主要终点
- Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28: African <=5 Years Per Protocol Population at Day 28 (PP28)
研究概览
简要总结
Primary Objective:
To determine whether a single dose combination of OZ439 (Artefenomel)/FQ (Ferroquine) was an efficacious treatment for uncomplicated Plasmodium falciparum malaria in adults and children.
Secondary Objectives:
-
To evaluate the efficacy of OZ439/FQ:
-
To determine the incidence of recrudescence and re-infection.
-
To determine the time to relief of fever and parasite clearance.
-
To evaluate the safety and tolerability of OZ439/FQ in adults and children.
-
To characterize the pharmacokinetics of OZ439 in plasma, FQ and its active metabolite SSR97213 in blood.
-
To determine the blood/plasma ratio for FQ and SSR97213 in some participants at limited time points in selected sites.
详细描述
Total duration was 63 days for each participant.
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)
入排标准
- 年龄范围
- 6 Months 至 69 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the body weight (BW), participants received orally a single dose of ferroquine (FQ) capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of artefenomel (OZ439) (maximum dose up to 800 milligrams [mg]) oral suspension as follows: BW greater than or equal to (>=) 35 kilograms (kg): FQ 400 mg + OZ439 800 mg; BW >=24 kg to less than (<) 35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.
干预措施: Ferroquine SSR97193 (Drug)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the body weight (BW), participants received orally a single dose of ferroquine (FQ) capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of artefenomel (OZ439) (maximum dose up to 800 milligrams [mg]) oral suspension as follows: BW greater than or equal to (>=) 35 kilograms (kg): FQ 400 mg + OZ439 800 mg; BW >=24 kg to less than (<) 35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.
干预措施: Artefenomel (Drug)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the body weight (BW), participants received orally a single dose of ferroquine (FQ) capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of artefenomel (OZ439) (maximum dose up to 800 milligrams [mg]) oral suspension as follows: BW greater than or equal to (>=) 35 kilograms (kg): FQ 400 mg + OZ439 800 mg; BW >=24 kg to less than (<) 35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.
干预措施: Placebo (Other)
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.
干预措施: Ferroquine SSR97193 (Drug)
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.
干预措施: Artefenomel (Drug)
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.
干预措施: Placebo (Other)
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.
干预措施: Ferroquine SSR97193 (Drug)
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.
干预措施: Artefenomel (Drug)
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.
干预措施: Placebo (Other)
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
干预措施: Ferroquine SSR97193 (Drug)
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
干预措施: Artefenomel (Drug)
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
干预措施: Placebo (Other)
结局指标
主要结局
Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28: African <=5 Years Per Protocol Population at Day 28 (PP28)
时间窗: Day 28
ACPR: negative parasitemia at Day 28, irrespective of axillary temperature(AT), in participants not meeting any criteria of early therapy failure (ETF):Danger signs (DS)/severe malaria (SM) at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count \>Day 0 irrespective of AT; or parasitemia at Day 3 with AT \>=37.5 degree Celsius (°C); or parasite count on Day 3\>=25 percent (%) on Day 0, or late clinical failure(LCF):DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT\>=37.5°C between Day 4 and 28, or late parasitological failure (LPF):presence of parasitemia between Day 7 and 28 and AT\<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection. In data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
次要结局
- Time to Recrudescence(Up to Day 63)
- Time to Re-infection(Up to Day 63)
- Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP Population at Day 42 (PP42)(Day 42)
- Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28: African <=5 Years PP28 Population(Day 28)
- Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP42 Population(Day 42)
- Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: African >5 Years Per Protocol Population at Day 28 (A5PP28)(Day 28)
- Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: Asian PP Population at Day 28 (APP28)(Day 28)
- Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP Population at Day 63 (PP63)(Day 63)
- Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP63 Population(Day 63)
- Time to Re-emergence(Up to Day 63)
- Parasite Clearance Time (PCT): African <=5 Years PP Population(From the start of study drug administration up to the time of the first negative film (up to Day 63))
- Parasite Clearance Time: African >5 Years PP Population(From the start of study drug administration up to the time of the first negative film (up to Day 63))
- Fever Clearance Time (FCT): African <=5 Years PP Population(From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63))
- Parasite Reduction Ratio at 24 Hours and 48 Hours: Asian PP Population(24 and 48 hours post dose)
- Pharmacokinetics (PK): Apparent Total Clearance of Artefenomel From Plasma After Oral Administration(2, 4, 6, 12, 24, 48, 72 and 672 hours post dose)
- Pharmacokinetics: Area Under the Curve From Time 0 to Day 28 (AUC0-day28) of Ferroquine(2, 4, 6, 8, 12, 24, 48, 168, 336 and 672 hours postdose)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)(From Baseline up to Day 63)
- Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine (Cmax)(2, 4, 6, 12, 24, 48, 72 and 672 hours post dose)
- Pharmacokinetics: Blood/Plasma Ratio for Ferroquine and Its Active Metabolite SSR97213(2, 4, 6, 12, 24, 48, 72 and 672 hours post dose)
- Parasite Clearance Time: Asian PP Population(From the start of study drug administration up to the time of the first negative film (up to Day 63))
- Parasite Reduction Ratio (PRRlog10) at 24 Hours and 48 Hours: African <=5 Years PP Population(24 and 48 hours post dose)
- Parasite Reduction Ratio at 24 Hours and 48 Hours: African >5 Years PP Population(24 and 48 hours post dose)
- Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration of Ferroquine(2, 4, 6, 12, 24, 48, 72 and 672 hours post dose)
- Fever Clearance Time: African >5 Years PP Population(From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63))
- Fever Clearance Time: Asian PP Population(From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63))
- Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Artefenomel(2, 4, 6, 12, 24, 48, 72 and 672 hours post dose)
- Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Artefenomel(2, 4, 6, 12, 24, 48, 72 and 672 hours post dose)
- Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration (Vss/F) of Artefenomel(2, 4, 6, 12, 24, 48, 72 and 672 hours post dose)
- Pharmacokinetics: Apparent Total Clearance of Ferroquine From Plasma After Oral Administration(2, 4, 6, 12, 24, 48, 72 and 672 hours post dose)