Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study With an Open-label Extension Period to Investigate the Efficacy and Safety of NT 201 in the Treatment of Children and Adolescents (2-17 Years) With Chronic Troublesome Sialorrhea Associated With Neurological Disorders, and/or Intellectual Disability
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 256
- 试验地点
- 31
- 主要终点
- Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4
研究概览
简要总结
The objective of this study is to investigate the efficacy and safety of NT 201 compared with placebo for the treatment of chronic troublesome sialorrhea associated with neurological disorders (e.g. cerebral palsy, traumatic brain injury) and/or intellectual disability in children and adolescents naïve to Botulinum neurotoxin treatment and aged 2-17 years.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female child/adolescent age 2-17 years.
- •Any neurological disorder (e.g. cerebral palsy or traumatic brain injury) and/or intellectual disability associated with chronic troublesome sialorrhea for at least 3 months up to the screening. In subjects with intellectual disability (ID) without neurological disorders, a diagnosis of ID by a specialist, e.g. pediatrician or by a center for developmental medicine is required for inclusion.
- •Severe drooling (modified Teacher´s Drooling Scale [mTDS] ≥ 6; clothing occasionally becomes damp) as rated by the investigator.
- •Parental consent and the subject's oral or written assent as the subject is able to provide.
排除标准
- •Chronic troublesome sialorrhea not related to neurological disorders and/or intellectual disability.
- •Body weight < 12 kg.
- •Pharmacological treatment for sialorrhea or concomitant medication known to influence sialorrhea strongly (e.g. anticholinergics with exception of locally applied or short acting drugs used under general anesthesia) within 45 days before baseline and during the entire study period.
- •Any previous known or suspected hypersensitivity to Botulinum toxin.
- •Aspiration pneumonia within 6 month before screening.
- •Any previous treatment with Botulinum toxin for any body region during the year before screening or within the screening period
- •Prior, concomitant or planned surgery or irradiation to head and neck to control sialorrhea (including salivary gland surgery or salivary gland irradiation) within one year before screening or planned for any part of the entire study period.
- •Concurrent diseases, including hematological, hepatic, renal, gastrointestinal, endocrine, pulmonary, musculoskeletal, or psychiatric diseases or conditions, which in the judgment of the investigator would put the subject at risk while in the study, could influence the results of the study, or negatively impact the subject's ability to participate in the study.
- •Extremely poor dental and/or oral condition that might preclude safe study participation by the judgment of the investigator.
- •Nursing mother or pregnant female subject.
研究组 & 干预措施
Double-blind MP: Placebo (Age 6 to 17 Years)
Participants will receive placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes will be matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
干预措施: NT 201 Placebo (Drug)
Double-blind, MP: NT 201 (Age 6 to 17 Years)
Participants will receive NT 201 (up to 2.5 Units per kilogram [U/kg] body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
干预措施: NT 201 (Drug)
Open-label, MP: NT 201 (Age 2 to 5 Years)
Participants will receive NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
干预措施: NT 201 (Drug)
OLEX: NT 201 (Age 6 to 17 Years)
Participants will receive NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm will consist of participants who will participate in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)".
干预措施: NT 201 (Drug)
OLEX: NT 201 (Age 2 to 5 Years)
Participants will receive NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).
干预措施: NT 201 (Drug)
结局指标
主要结局
Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4
时间窗: Baseline and Week 4
This endpoint was planned to be analyzed in double-blind, MP, 6 to 17 years participants only. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and the procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea.
Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s)
时间窗: Week 4
This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
时间窗: Baseline up to Week 64
次要结局
- Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle(Baseline up to Week 64)
- GICS at Weeks 8 and 12(Weeks 8 and 12)
- Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle(Baseline up to Week 64)
- Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle(Baseline up to Week 64)
- Change From Baseline in uSFR at Weeks 8 and 12(Baseline and Weeks 8 and 12)
- Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle(Baseline up to Week 64)