AFQ056 for Language Learning in Children With FXS
Condition: Fragile X Syndrome
MeSH terms: Fragile X Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): AFQ056; Placebo; Language Intervention
Intervention type(s): Drug; Drug; Other
Intervention description(s): 12.5 mg - 100 mg oral suspension (liquid); Placebo oral suspension (liquid); All subjects will begin an intensive language intervention 2 months after starting treatment with AFQ056 or placebo and will continue the intervention through the end of the study.
The language intervention will be administered by a trained language specialist through a combination of in clinic visits and at home synchronous video conferencing sessions. The intervention will subsequently be delivered to the parent by a speech-language clinician through weekly clinician coaching, homework, and feedback sessions.
The language intervention is designed to help parents learn and use verbally responsive interactional strategies more frequently and effectively throughout the course of their daily interactions with their children.
Other intervention name(s): Mavoglurant
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The trial will use a double-blind placebo-controlled parallel-group flexible-dose forced titration design. 100 eligible subjects with Fragile X Syndrome age 32 months to 6 years will enter a 4-month single-blind placebo lead-in period, followed by an 8-month double-blind treatment period during which subjects will randomized 1:1 to AFQ056 or placebo and will receive 6 months of language intervention. Subjects will then be invited to participate in an open-label extension phase during which all participants will receive treatment with active drug and continue language intervention for up to 8 months.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment