Safety and Efficacy of AFQ056 in Adult Patients With Fragile X Syndrome

Study Overview
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Brief Summary
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This Phase IIb study is designed to assess whether 3 doses of AFQ056 are safe and effective in treating the behavioral symptoms of Fragile X Syndrome.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate AFQ056 in Adult Patients With Fragile X Syndrome

Conditions
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Fragile X Syndrome

Intervention / Treatment
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* Drug: AFQ056
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Fragile X Syndrome, who are at least moderately ill based on a Clinical Global Impression Severity score of at least 4 and have qualifying scores on the ABC-C and IQ test at Visit 1 Exclusion Criteria: Advanced, severe or unstable disease that may interfere with the study outcome evaluations Cancer within the past 5 years, other than localized skin cancer Current treatment with more than two psychoactive medications, excluding anti-epileptics History of severe self-injurious behavior Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25 mg bid AFQ056<br>1 capsule of 25 mg and 1 capsule of placebo per intake | Drug: AFQ056<br>* AFQ056, was provided as hard gelatin capsules, 25mg and 100 mg oral dosage strengths, identical in appearance were used<br>|
| Experimental: 50 mg bid AFQ056<br>2 capsules of 25 mg per intake | Drug: AFQ056<br>* AFQ056, was provided as hard gelatin capsules, 25mg and 100 mg oral dosage strengths, identical in appearance were used<br>|
| Experimental: 100 mg bid AFQ056<br>1 capsule of 100 mg and 1 capsule of placebo per intake | Drug: AFQ056<br>* AFQ056, was provided as hard gelatin capsules, 25mg and 100 mg oral dosage strengths, identical in appearance were used<br>|
| Placebo Comparator: Placebo<br>2 capsules of placebo per intake | Drug: Placebo<br>* Placebo medication identical in appearance to active medication was provided<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in behavioral symptoms of Fragile X Syndrome using the Aberrant Behavior Checklist - Community (ABC-C) Total score in Stratum I | The ABC-C is a 58-item questionnaire that should have been completed as much as possible by the same rater. It is comprised of five subscales (irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity and inappropriate speech) plus the total score which ranks from 0 to 174 in patients who were fully methylated (FM) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in behavioral symptoms of Fragile X Syndrome (FXS) using the ABC-C Total score in Stratum II | The ABC-C is a 58-item questionnaire that should have been completed as much as possible by the same rater. It is comprised of five subscales (irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity and inappropriate speech). Assessing the reduction in the (ABC-C) total score after 12 weeks of treatment in FXS patients with partially methylated (PM) FMR1 gene. | 12 weeks | 
| Global improvement of symptoms in Fragile X using the Clinical Global Impression-Improvement (CGI-I) scale | The CGI-I score ranges from 1 to 7 (with 1 being very much improved, 4 being no change to 7 being very much worse) | 12 weeks | 
| Change from baseline in irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity, and inappropriate speech assessed by the individual subscales of the ABC-C scale | comprised of five subscales (irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity and inappropriate speech) plus the total score which ranks from 0 to 174 | 12 weeks | 
| The proportion of patients with clinical response in the ABC-C total score | response is defined as reduction of at least 25% from baseline in the ABC-CFX total score and a score of 1 (very much improved) or 2 (much improved) on the CGI-I scale at Week 12 | 12 weeks | 
| improvement of repetitive behavior as measured by changes in the RBS-R | The Repetitive Behavior Scale - Revised (RBS-R) includes six domains: ritualistic behavior, sameness behavior, stereotypic behavior, self-injurious behavior, compulsive behavior, and restricted interests. A negative change from baseline indicates improvement | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fragile X Syndrome, Martin-Bell Syndrome, Genetic Diseases, X-Linked