Summary

for people ages 32 months to 6 years (full criteria)
at Davis, California and other locations
study started
estimated completion
Randi Hagerman, MD

Description

Summary

The overall goals are to change the paradigm for development of mechanism targeted pharmacotherapy in neurodevelopmental disorders and provide a definitive test of the mGluR theory in humans by determining whether AFQ056, an mGluR5 negative modulator, can enhance neural plasticity in the form of language learning during an intensive language intervention in very young children with fragile X syndrome. This trial therefore will use an innovative but exploratory new trial design to develop a different way to examine efficacy of an agent with substantial support as a drug targeting CNS plasticity in preclinical models of a developmental disorder. If the design is successful, this trial can serve as a model for future trials of mechanistically-targeted treatments operating on neural plasticity in other neurodevelopmental disorders.

Official Title

Effects of AFQ056 on Language Learning in Young Children With Fragile X Syndrome (FXS)

Details

The trial will use a double blind placebo-controlled parallel-group flexible-dose forced titration design in which 100 subjects with FXS, age 32 months to 6 years of age will enter a 12-month blinded treatment phase during which they are randomized 1:1 to AFQ056 or placebo followed by an 8-month (open label) extension phase in which all participants will be treated with active drug. The flexible dose design will mimic practice, take into account differential responsiveness and the known inter-child variability in drug levels with AFQ056, and allow use of maximum tolerated dose (MTD) which is likely to be most effective.

Keywords

Fragile X Syndrome Syndrome AFQ056 Language Intervention

Eligibility

You can join if…

Open to people ages 32 months to 6 years

  1. Age 32 months to 6 years inclusive at Screening (visit 1).
  2. Has an FMR1 full mutation.
  3. DQ<75 calculated from the Mullen Scales of Early Learning at time of screening.
  4. Parent or legal guardian is available and able to communicate well with the investigator, comply with study requirements and provide written informed consent.

NoteThe Parent or legal guardian who will be signing consent form, should be the individual administering the language intervention

  1. English is the primary language spoken in the home and the subject's first language is English.
  2. Meet criteria indicating evidence of intentional communication based on parent interview via a communication eligibility screening tool.

Note On the Eligibility Screening Tool - Communication, the child must have at time of screening:

  1. Section 1: Answer of YES; the child uses at least 5 spoken words to label items on a daily basis.

OR

  1. Section 2: At least 3 YES answers to items 1-10 if child does not have at least 5 spoken words.
  2. Produces 3 or more intentional acts of communication on the structured portion of the Weighted Communication play sample at time of screening.
  3. Stable behavioral and other therapy regimen for 30 days prior to screening.
  4. Stable dosing of all concurrent psychotropic medications except stimulants for at least 60 days prior to screening. Due to the very short half-life of stimulants (specifically methylphenidate and amphetamine variants), a stable regimen of these medications is required for 2 weeks only.
  5. Note** Medications impacting GABA, glutamate and/or mGluR5 pathway receptors are exclusionary and not permitted during study participation. Additionally, stimulant regimens may include combinations of short- and long-acting forms and may be taken with different timing or dosing on different days of the week (e.g. Doses may be skipped on weekends or days off school and extra doses may be given some days for therapy sessions later in the day). The intent is to keep the doses and regimen being used at the time of screening consistent during the trial even if there is some variation in how the medication is taken on different days.

You CAN'T join if...

  1. Use of medications impacting GABA, glutamate and/or mGluR5 pathway receptors or transmission.

Note Treatment with acamprosate, amantadine, budipine, carbetocin, cycloserine, dextromethorphan, felbamate, ketamine, lithium, minocycline, memantine, oxytocin, remacemide, racemic baclofen, riluzole, fycampa, investigational mGluR5 medications, and/or statins are exclusionary.

  1. Unstable seizure disorder as defined by any seizure in the 6 months prior to the screening visit, and/or any change in anti-convulsant drug dosing in the 60 days prior to screening.

Note Use of levetiracetam and oxcarbazepine are among permitted anticonvulsants.

  1. Use of any other investigational drug at the time of enrollment or within 30 days or 5 half-lives (whichever is longer) of the investigational drug prior to screening until end of study visits (or longer if required by local regulations).
  2. History of hypersensitivity to AFQ056 or any mGluR antagonist.
  3. History or presence of any clinically significant disease of any major system organ class, within the past 2 years prior to screening including but not limited to neurological, cardiovascular, endocrine, metabolic, renal, or gastrointestinal disorders. This does not include typical features of FXS such as psychological symptoms or history of epileptic seizures.
  4. Significant acute illness that did not completely resolve at least four weeks prior to the Screening visit.
  5. Abnormal laboratory values at screening that are in the opinion of the investigator are clinically significant and may jeopardize the safety of the study subject.
  6. Use of (or use within at least 5 half-lives before dosing) concomitant medications that are strong/moderate inhibitors or inducers of CYP1A1/2, CYP2C9/19 or CYP3A4 (see Appendix B).
  7. Subjects who are, in the opinion of the investigator, unable to comply with the requirements of the study.
  8. . History or Ppresence of immunodeficiency diseases at the time of screening, based on medical history, including a positive HIV test result.
  9. . History of a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C result at time of screening.
  10. . History or presence of suicidal thoughts and/or suicide attempts.

Locations

  • Univeristy of California - Davis accepting new patients
    Davis California 95817 United States
  • Children's Hospital of Colorado accepting new patients
    Denver Colorado 80045 United States

Lead Scientist

  • Randi Hagerman, MD
    Professor, General Pediatrics. Authored (or co-authored) 472 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Elizabeth Berry-Kravis
Links
Sign up for this study
ID
NCT02920892
Phase
Phase 2
Study Type
Interventional
Last Updated