Effects of AFQ056 on Language Learning in Young Children With Fragile X Syndrome (FXS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 110
- 试验地点
- 14
- 主要终点
- Change in Weighted Child Intentional Communication Score
研究概览
简要总结
The purpose of this clinical trial is to investigate the impact of AFQ056 on language learning in 3-6 year old children with Fragile X Syndrome (FXS).
详细描述
This study will enroll 100 participants with Fragile X syndrome (FXS) between the ages of 32 months and 6 years.
After being informed about the study and its potential risks, patients with Fragile X Syndrome will be screened for eligibility. Participants who meet entry criteria and agree to participate will then enter a single-blind 4-month placebo lead-in during which study participants will continue therapy treatments as usual to allow for placebo effects to stabilize. At the end of the 4-month placebo lead-in, all participants will have a repeat battery of AFQ056 baseline assessments and will enter the placebo-controlled phase, where they will be randomized in a 1:1 ratio to AFQ056 or placebo. All subjects will begin at a dose of 25 mg of AFQ056 or placebo, taken orally twice per day. Over 7 weeks, they will titrate up to their maximum tolerated dose (MTD), up to 100 mg. Once they have reached their MTD, both participant groups will initiate an intensive language intervention designed to maximize the extent to which parents engage in types of verbally responsive interactions that have been well documented as facilitating language learning. The entire language intervention will be delivered to the parent in the home or at scheduled study visits through the use of a laptop computer equipped with distance video-teleconferencing software and will include coaching, homework, and feedback sessions. Subjects will be treated with their MTD in combination with the language intervention for 6 months.
After 8 months of treatment in the placebo-controlled phase (including 6 months of language intervention), all participants will have final assessments and will be given the opportunity to enter the open label extension (OLE) period. In the OLE, all participants will be treated with active drug according to the same schedule as in the placebo-controlled phase with 2 months of flexible dose titration to the MTD followed by a period of stable treatment, and will continue the language intervention throughout. A post-intervention follow-up visit will be conducted one month after the final assessment visit of the trial.
Researchers will compare overall weighted communication score in the AFQ056 and placebo groups, after 6 months of treatment in combination with an intensive standardized parent-implemented language learning intervention. This is meant to serve as a marker of drug effect on neural plasticity, the core problem in the disorder. Further assessments will also be compared between groups to determine changes in language, cognitive, and adaptive functioning.
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)
盲法说明
After screening assessments, participants who met entry criteria and agreed to participate entered a single-blind 4-month placebo lead-in during which study participants had therapy treatments as usual to control for the effects of the language intervention. The 4-month placebo lead-in allowed for placebo effects to stabilize.
At the end of the 4-month placebo lead-in, all participants will enter a double blind placebo controlled phase in which they will have a repeat battery of AFQ056 baseline assessments and will be randomized 1:1 to AFQ056 or placebo. Both treatment groups received an intensive language intervention for 6 months after 2 months of flexible dose titration to establish their maximum tolerated dose (MTD).
After 8 months of treatment in the placebo-controlled phase (including 6 months of language intervention), all participants had final assessments and entered the open label extension (OLE) of about 8 months.
入排标准
- 年龄范围
- 32 Months 至 6 Years（Child）
- 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
Double-Blind AFQ056 with language intervention
After a 4-month single-blind placebo lead-in period, subjects with FXS were randomized to receive AFQ056 suspension by mouth twice per day in an 8 month double-blind treatment period.
During the double-blind treatment period, subjects in the AFQ056 treatment group began with a dose of 25 mg AFQ056 twice per day and titrated to their maximum tolerated dose over the course of 7 weeks. After 7 weeks the dose was fixed, and at the 2 month visit, the intensive language intervention was initiated. Subjects continued the language intervention while remaining on a stable dose of AFQ056 (ranging from 12.5 mg BID to 100 mg BID), for the next 6 months.
Safety and efficacy assessments were performed throughout.
干预措施: AFQ056 (Drug)
Double-Blind AFQ056 with language intervention
After a 4-month single-blind placebo lead-in period, subjects with FXS were randomized to receive AFQ056 suspension by mouth twice per day in an 8 month double-blind treatment period.
During the double-blind treatment period, subjects in the AFQ056 treatment group began with a dose of 25 mg AFQ056 twice per day and titrated to their maximum tolerated dose over the course of 7 weeks. After 7 weeks the dose was fixed, and at the 2 month visit, the intensive language intervention was initiated. Subjects continued the language intervention while remaining on a stable dose of AFQ056 (ranging from 12.5 mg BID to 100 mg BID), for the next 6 months.
Safety and efficacy assessments were performed throughout.
干预措施: Language Intervention (Other)
Double-Blind Placebo with language intervention
After a 4-month single-blind placebo lead-in period, subjects with FXS were randomized to receive a placebo suspension by mouth twice per day in an 8 month double-blind treatment period.
During the double-blind treatment period, dose titration to maximum tolerated dose of matching placebo occurred over 7 weeks. After 7 weeks, the dose was fixed, and at the 2 month visit, the intensive language intervention was initiated. Subjects continued the language intervention while remaining on placebo for the next 6 months.
Safety and efficacy assessments were performed throughout.
干预措施: Placebo (Drug)
Double-Blind Placebo with language intervention
After a 4-month single-blind placebo lead-in period, subjects with FXS were randomized to receive a placebo suspension by mouth twice per day in an 8 month double-blind treatment period.
During the double-blind treatment period, dose titration to maximum tolerated dose of matching placebo occurred over 7 weeks. After 7 weeks, the dose was fixed, and at the 2 month visit, the intensive language intervention was initiated. Subjects continued the language intervention while remaining on placebo for the next 6 months.
Safety and efficacy assessments were performed throughout.
干预措施: Language Intervention (Other)
Open-Label AFQ056 with language intervention
After 8 months of treatment in the placebo-controlled phase, all subjects had assessments completed and were given the opportunity to enter the open-label extension (OLE) in which all subjects received AFQ056. The OLE began with 2 months of flexible dose titration to each subject's maximum tolerated dose followed by a period of stable treatment. Subjects also continued the language intervention through the extension phase.
The duration of the stable treatment depended on when the subject was enrolled into the study. Those enrolled prior to June 15-30, 2019 received a 6-month period of stable treatment. Those enrolled after June 15, 2019 had their period of stable treatment shortened on a sliding scale, such that their treatment including weaning, if necessary, ended before August 31, 2021 (study drug expiration).
干预措施: AFQ056 (Drug)
Open-Label AFQ056 with language intervention
After 8 months of treatment in the placebo-controlled phase, all subjects had assessments completed and were given the opportunity to enter the open-label extension (OLE) in which all subjects received AFQ056. The OLE began with 2 months of flexible dose titration to each subject's maximum tolerated dose followed by a period of stable treatment. Subjects also continued the language intervention through the extension phase.
The duration of the stable treatment depended on when the subject was enrolled into the study. Those enrolled prior to June 15-30, 2019 received a 6-month period of stable treatment. Those enrolled after June 15, 2019 had their period of stable treatment shortened on a sliding scale, such that their treatment including weaning, if necessary, ended before August 31, 2021 (study drug expiration).
干预措施: Language Intervention (Other)
结局指标
主要结局
Change in Weighted Child Intentional Communication Score
时间窗: Baseline through Month 8
The Weighted Child Intentional Communication Score is derived from a 22 minute semi-structured examiner/child play session. Structured and unstructured component scores are found by multiplying each intentional communication act by the following weights: nonverbal = 1; single symbol = 2; and multiple symbols = 3. The two scores are summed together to obtain the total. Higher scores indicate more child-initiated communication. There is no maximum score. The scale was administered at Baseline, Month 2, Month 4, Month 6, and Month 8. A composite score representing the average of the estimated change scores calculated at months 2, 4, 6, and 8 was recorded. A higher least squares mean value indicates a greater increase in WCS score from baseline.
次要结局
- Change in Mullen Scales of Early Learning (MSEL) Developmental Quotient (DQ)(Baseline through Month 8)
- Change in Mullen Scales of Early Learning (MSEL) Expressive Language Subscore(Baseline through Month 8)
- Change in Vineland Adaptive Behavior Scale (Vineland-3) Composite Score(Baseline through Month 8)
- Change in Vineland Adaptive Behavior Scale (Vineland-3) Communication Subscore(Baseline and Month 8)
- Change in Preschool Language Scale (PLS-5) Expressive Communication Score(Baseline and Month 8)
- MacArthur-Bates Communicative Development Inventory (CDI) Number of Spoken Words(Month 8)
- Number of Participants With a Positive Response as Defined by Improvement in Clinical Global Impression - Improvement (CGI-I) Overall Function Scores(Month 8)
研究者
Elizabeth Berry-Kravis
Professor of Pediatrics, Neurological Sciences, Biochemistry
Rush University Medical Center