Safety and Efficacy of Combination Therapy With Ivermectin, Diethylcarbamazine, and Albendazole (IDA) for Individuals With Onchocerciasis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 154
- 试验地点
- 1
- 主要终点
- Percentage of Worms Killed Across Study Arms
研究概览
简要总结
This DOLF study will investigate the safety and effectiveness of IDA treatment in persons with onchocerciasis when it is administered after pre-treatment with ivermectin to clear or greatly reduce microfilariae from the skin and eyes.
详细描述
This study will provide preliminary data on the safety of IDA treatment in persons with onchocerciasis when it is administered after pre-treatment with IVM to clear or greatly reduce microfilariae from the skin and eyes. Widespread use of IDA following IVM pretreatment (I/IDA) has the potential to greatly accelerate elimination of lymphatic filariasis (LF) in African countries that are co-endemic for LF and onchocerciasis. study later.
This study will also assess the efficacy of IDA for killing and sterilizing adult filarial worms. An improved macrofilaricidal treatment would be a major advance for the global program to eliminate onchocerciasis. Since the safety and efficacy objectives are both very important, we have included dual primary objectives for the study.
Primary objectives:
- Safety: To compare rates and types of severe adverse events (grade 3 or higher) that occur within 7 days following 1 day or 3 days of treatment with triple drug treatment ("IDA" = diethylcarbamazine (DEC) with ivermectin (IVM) and albendazole (ALB)) with the comparator regimen of 1 day of treatment with ivermectin and albendazole (IA) in persons with active Onchocerca volvulus infections after pretreatment with ivermectin alone.
- Efficacy: To compare the effect of three treatment regimens (1 day of IDA, 3 days of IDA, or IA) for killing or sterilizing adult female O. volvulus worms based on the percentage of all adult female worms in nodules that are alive with embryos in the uterus 18 months after treatment.
This is an open label, randomized clinical trial.
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
- None
盲法说明
While this is an open label study and there is no placebo treatment group, all efforts will be made to ensure that that medical/technical staff assessing skin Mf, adverse events (AEs) and ophthalmological findings will be unaware of initial baseline skin and ocular Mf findings and treatment arm as best as possible.
入排标准
- 年龄范围
- 16 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women who were previously enrolled in the preceding Part I study (Protocol ID#201804116) and residing in the study area
- •Must have at least palpable subcutaneous nodule (onchocercoma)
- •Participants with baseline skin Mf counts less than or equal to 3 Mf/mg at the time of enrollment into the Part I study (Protocol ID#201804116)
排除标准
- •Pregnant and breastfeeding mothers within 1 month of giving birth
- •Severe eye disease at baseline including uveitis, severe glaucoma, severe keratitis, and/or cataracts that interfere with visualization of the posterior segment of the eye as well as the list of ocular diseases as outlined below. All ocular disease exclusion criteria apply to either eye. Bilateral disease is not necessary to exclude a participant. A participant will be excluded if any of the criteria are met for one eye.
- •Any cataract of any type preventing clear visualization of fundus or imaging on Optical Coherence Tomography (OCT).
- •Severe retinal nerve fiber layer thinning in the superior and inferior quadrant analysis on Ocular Coherence Tomography of the optic nerve with a corresponding visual field defect of grade 2 or worse on the same eye.If Ocular Coherence Tomography is not available, the following exclusion criteria will apply: vertical Cup/disc ratio on fundoscopy (not by OCT reading) greater than or equal to 0.
- •Intraocular pressure (IOP) greater than or equal to 25 by Goldmann tonometry .12
- •Retinal Detachment or Retinal Break
- •Acute ocular infection (i.e., Viral conjunctivitis, corneal ulcer, endophthalmitis)
- •Optic Atrophy with visual field defect reproducible on confrontation visual field testing..
- •Exam consistent with Herpes Simplex Virus eye infection
- •Homonymous hemianopsia, quadrantanopsia, bitemporal hemianopsia, or central scotoma related to cerebral vascular disease by Automated Visual Field testing and confrontation visual field testing.
- •Acute Angle Closure Glaucoma
- •Gonioscopy grade 0 (slit) limiting ability to safely dilate patient
- •Severe Tremor, blepharospasm, or other voluntary or involuntary motor condition that prevents ability to examine patient with slit lamp, OCT, gonioscopy, IOP measurement, fundus photography, and Frequency doubling technology perimetry.
- •Cognitive impairment sufficient to prevent ability to understand and perform Visual Acuity Test with Tumbling E chart, confrontation visual field, slit lamp exam, or any other ocular exam component.
- •Optic nerve edema
- •Active retinopathy or retinitis not attributable to onchocercal disease
- •History of uveitis not associated with onchocercal disease
- •Any pre-existing chorioretinal scar or retinal degeneration and other significant retinal pathologies (foveomacular schisis, dystrophies, arterial macroaneurysms etc) involving the macula.
- •Severe ocular pain, that patient rates as 9 or 10 out of 10 pain.
- •Best corrected or pinhole visual acuity worse than 6/60 (20/200)
- •Age related macular degeneration (AMD)
- •Significant comorbidities such as renal insufficiency, liver failure, or any other acute or chronic illness identified by study clinicians and investigators that interferes with the participant's ability to go to school or work or perform routine household chores.
- •Prior allergic / hypersensitivity reactions or intolerance to IVM, ALB, or DEC.
- •Treatment with IVM outside of the study after the pre-treatment clearing dose provided in the Part I study.
- •>5 motile Mf in the anterior chamber in either eye at the time of enrollment (after pre-treatment with IVM).
- •Any Mf identified in the posterior segment of the eye at the time of enrollment (six months after pre-treatment with IVM).
- •Any other condition identified by study clinicians or investigators that may preclude participation in the study.
研究组 & 干预措施
IVM + ALB
Single dose of oral IVM (150 µg/kg) plus ALB (400 mg)
干预措施: IVM w/ ALB (Drug)
IDA x 1 dose
Single dose of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
干预措施: Single dose of IDA (Drug)
IDA x 3 doses
Once daily for 3 days oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
干预措施: Three daily doses of IDA (Drug)
结局指标
主要结局
Percentage of Worms Killed Across Study Arms
时间窗: 18 months following treatment.
The effect of three treatment regimens for killing adult female O. volvulus worms will be compared based on the percentage of all adult female worms in nodules that are alive with embryos in the uterus 18 months after treatment.
Rates of Severe Adverse Events (SAEs) Across Study Arms
时间窗: Within 7 days following end of treatment
Rates of severe adverse events (grade 3 or higher) following 1-day or 3-day triple drug treatment will be compared against those of the comparator regimen of 1 day of IVM/ALB.
Percentage of Worms Sterilized Across Study Arms
时间窗: 18 months following treatment.
The effect of three treatment regimens for sterilizing adult female O. volvulus worms will be compared based on the percentage of all adult female worms that are fertile in the nodules 18 months after treatment.
次要结局
- Effectiveness for Preventing Reappearance of Microfilariae in the Skin by Skin Snips(Baseline, 12 months, and 18 months following treatment)
- Rates of SAEs by Treatment Group in Those With Intraocular Microfilariae Just Prior to Treatment With IDA(within 7 days following end of treatment)
- Rates of Ocular Adverse Events (Any Grade) by Treatment Group(within 3 months of treatment with IDA)
- Effectiveness of Killing Adult Female Worms(18 months following treatment)
- Effectiveness of Clearing Microfilariae From Skin by Skin Snips(Baseline, 3 months, 12 months, & 18 months following treatment.)