An Adaptive Phase II/III SingleBlinded, Randomized, MultiCentre, ParallelGroup, Active Controlled, Superiority Study to Evaluate the Safety and Efficacy of a Single Day or 3day Single Dose of an ALBENDAZOLE IVERMECTIN Coformulation vs ALBENDAZOLE for the Treatment of SoilTransmitted Helminth Infections (Trichuris Trichiura, Hookworm, Strongyloides Stercoralis) in Paediatric and Young Adult Population
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1,001
- 试验地点
- 3
- 主要终点
- Cure Rate for T. Trichiura (CR)
研究概览
简要总结
The purpose of this clinical trial is to evaluate a fixed-dose co-formulation (FDC) of ivermectin and albendazole for the treatment of all Soil Transmitted helminths (STH). The current strategy to control STH in endemic areas is mass administration of albendazole or mebendazole, mainly to pre-school and school-aged children.
Although this treatment works well for some STH species, efficacy against Trichuris trichiura is poor and it is not effective Strongyloides stercoralis. Thus new drugs or drug combinations are an urgent priority to increase the effectiveness of control programmes. Furthermore, the World Health Organisation has recommended combination therapy of ivermectin with albendazole. The trial proposed, is an adaptive phase II/III trial where the phase II component will evaluate the safety of the FDC as a single dose or 3-day single dose regimen for the treatment of T. trichiura in paediatric population. After analysis of the safety results the phase III trial will be executed to evaluate the efficacy of the FDC as a single dose or 3-day single dose regimen compared to the standard single dose regimen of ALB (400 mg) for the treatment of T. trichiura, hookworm and S. stercoralis in paediatric and young adult population. The estimated total sample size for the adaptive design (phase II and III component) is 1223 participants. Of these, 126 will be enrolled in the phase II and 1097 in the phase III components respectively in an adaptive trial design.
详细描述
An adaptive phase II/III clinical trial to evaluate the Safety and Efficacy of a Single Day or 3-day Single Dose of an ALBENDAZOLE-IVERMECTIN Coformulation vs ALBENDAZOLE for the Treatment of Soil-Transmitted Helminth Infections. The estimated total sample size for the adaptive design (phase II and III components) is 1223 participants. Of these, 126 will be enrolled in the phase II and 1097 in the phase III components.
Phase II component (Kenya only)
Unicentric, 3-arm, parallel, open-label, individually randomised, phase II trial to determine in three weight groups, the safety of the ALBENDAZOLEIVERMECTIN Co-formulation given as a Single Day or 3-day Single Dose regimen for the treatment of Trichuris trichiura in children and young adult aged between 5 to 18 years. Estimated sample size: 126 participants Participants will be stratified in three different weight groups in order to gradually increase the dose of ivermectin in the Fixed Dose Co-formulation (FDC):
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Group 1 (38 participants): with body weight of 23-<30 Kg will receive 300-391 µg/Kg IVM (FDC 400mg-9mg) or ALB
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Group 2 (38 participants): with body weight of 30-45 Kg will receive 400-600 µg/Kg IVM (FDC 400mg-18mg) or ALB.
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Group 3 (50 participants): with body weight of 15-23 Kg will receive 391-600 µg/Kg IVM (FDC 400mg-9mg) or ALB. Where FDC stands for Fixed Dose Co-formulation and ALB stands for Albendazole. Then, the participants will be allocated to one of the three study arms with unequal probability (ALB: p=0.2, n=26; FDCx1: p=0.4, n=50; FDCx3: p=0.4, n=50) starting with group 1.
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Treatment Arm 1: Single dose of a tablet of ALBENDAZOLE 400 mg (active control arm).
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Treatment Arm 2: Single dose of a tablet of ALBENDAZOLEIVERMECTIN Co-formulation.
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Treatment Arm 3: Daily dose of a tablet of ALBENDAZOLE-IVERMECTIN Co-formulation for 3 consecutive days.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Positive infection test by microscopy for at least one of the following STH: T. trichiura, hookworms and/or larvae of S. stercoralis.
- •Weight ≥15 Kg.
- •Male or female, aged 5 to 18 years.
- •Female participants who are ≥12 years old (or female post menarche) must have a negative urine pregnancy test at screening or at the time of randomization.
- •Ability to take oral medication and willingness to comply with all study procedures.
- •Parental acceptance to participate in the study by obtaining a signed and dated informed consent form approved by the Regulatory authorities. In addition, verbal assent will be obtained from children aged 12-18 years.
排除标准
- •Intake of ALB, mebendazole and/or IVM, or any potentially interacting drug three months before screening.
- •Residence outside the study area or planning to move away in the four weeks following recruitment.
- •Epidemiological risk of infection by Loa loa.
- •Serious medical illness, per investigator's criteria.
- •Any participant's condition that would prevent the appropriate evaluation and followup, as per investigator's criteria.
- •Known hypersensitivity to any components of either of the study treatment.
- •Positive pregnancy urine test, pregnant or first week postpartum.
研究组 & 干预措施
Albendazole
Albendazole 400 mg single dose
干预措施: Albendazole (Drug)
FDCx1. Albendazole and Ivermectin Fixed Dose Coformulation
Single dose of a tablet of FDC 400mg18mg or 400mg9mg. (i) For participants <45 kg of body weight at baseline: FDC of 400mg ALB 9mg IVM. (ii) For participants ≥45 kg of body weight at baseline: FDC of 400mg ALB18mg IVM
干预措施: Albendazole and Ivermectin fixed dose coformulation (Combination Product)
FDCx3. Albendazole and Ivermectin Fixed Dose Coformulation 3 days
Daily dose of a tablet of FDC 400mg18mg or 400mg 9mg for 3 days. (i)For participants <45 kg of body weight at baseline: FDC of 400mg ALB9mg IVM. (ii) For participants ≥45 kg of body weight at baseline: FDC of 400mg ALB 18mg IVM.
干预措施: Albendazole and Ivermectin fixed dose coformulation (Combination Product)
结局指标
主要结局
Cure Rate for T. Trichiura (CR)
时间窗: 21 days
For Trichuris trichiura, the cure rate is defined as the proportion of participants who test negative for T. trichiura eggs in the Kato-Katz fecal examination on day 21 post-treatment, relative to the total number of participants infected at baseline (n=636).
Frequency of Related Adverse Events
时间窗: 21 days postreatment
Proportions of participants presenting at least one treatment-related adverse event by arm
次要结局
- Egg Reduction Rate for T. Trichiura (ERR)(21 days)
- Cure Rate for for Hookworm (CR)(21 days)
- Egg Reduction Rate for Hookworm (ERR)(21 days)
- Cure Rates for for S. Stercoralis(21 days)
- Cure Rate for T. Trichiura (CR) by qPCR(21 days)
- To Evaluate the Frequency of Known ALB Resistant Alleles in Hookworm and T. Trichiura in the Three Treatment Arms Before and After Treatment.(21 days)