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

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ClinicalTrials.gov Identifier: NCT01357239
Recruitment Status : Completed
First Posted : May 20, 2011
Results First Posted : May 12, 2015
Last Update Posted : May 12, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Fragile X Syndrome Drug: AFQ056 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 139 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of AFQ056 in Adolescent Patients With Fragile X Syndrome
Study Start Date : May 2011
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 25 mg bid Drug: AFQ056
Experimental: 50 mg bid Drug: AFQ056
Experimental: 100 mg bid Drug: AFQ056
Placebo Comparator: Placebo Drug: Placebo



Primary Outcome Measures :
  1. Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the Aberrant Behavior Checklist-Community Edition (ABC-CFX) Total Score in Stratum I Patients Exposed to AFQ056 100 mg Bid [ Time Frame: Baseline to week 12 ]
    The Aberrant Behavior Checklist-Community edition (ABC-C) is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales (irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity, inappropriate speech and social avoidance) plus the total score were considered, and for which the total score ranks from 0 to 165. Stratum I included patients whose Fragile X Mental Retardation 1 (FMR1) gene was fully methylated


Secondary Outcome Measures :
  1. Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the ABC-CFX Total Score in Stratum II Patients Exposed to All 3 Doses of AFQ056 [ Time Frame: Baseline to week 12 ]
    The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales (irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity, inappropriate speech and social avoidance) plus the total score were considered, and for which the total score ranks from 0 to 165. Stratum II included patients whose FMR1 gene was partially methylated

  2. Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the ABC-CFX Total Score in Stratum I Patients Exposed to the Two Lower Doses of AFQ056 (25 mg Bid and 50 mg Bid) [ Time Frame: Baseline to week 12 ]
    The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales (irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity, inappropriate speech and social avoidance) plus the total score were considered, and for which the total score ranks from 0 to 165. Stratum I included patients whose FMR1 gene was fully methylated

  3. Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum I Patients [ Time Frame: 12 weeks ]
    The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum I included patients whose FMR1 gene was fully methylated.

  4. Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum II Patients [ Time Frame: 12 weeks ]
    The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum II included patients whose FMR1 gene was partially methylated

  5. Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I [ Time Frame: 12 weeks ]
    The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum I included patients whose FMR1 gene was fully methylated.

  6. Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II [ Time Frame: 12 weeks ]
    The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum II included patients whose FMR1 gene was partially methylated

  7. Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum I [ Time Frame: Baseline to week 12 ]
    The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales: irritability (range 0 to 54); lethargy/withdrawal (range 0 to 39); stereotypic behavior (range 0 to 18); hyperactivity (range 0 to 30); inappropriate speech (range 0 to 12); and social avoidance (range 0 to 12) plus the total score (range 0 to 165) were considered. A negative change represents improvement. Stratum I included patients whose FMR1 gene was fully methylated

  8. Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech, and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum II [ Time Frame: Baseline to week 12 ]
    The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales: irritability (range 0 to 54); lethargy/withdrawal (range 0 to 39); stereotypic behavior (range 0 to 18); hyperactivity (range 0 to 30); inappropriate speech (range 0 to 12); and social avoidance (range 0 to 12) plus the total score (range 0 to 165) were considered. A negative change represents improvement. Stratum II included patients whose FMR1 gene was partially methylated

  9. Proportion of Patients With Clinical Response, Where Response is Defined as a 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, Stratum I [ Time Frame: 12 weeks ]
    The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to ABC-CFX algorithm, for which 55 items and six subscales plus the total score were considered, and for which the total score ranks from 0 to 165. The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum I included patients whose FMR1 gene was fully methylated; Stratum II included patients whose FMR1 gene was partially methylated.

  10. Proportion of Patients With Clinical Response, Where Response is Defined as a 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, Stratum II [ Time Frame: 12 weeks ]
    The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to ABC-CFX algorithm, for which 55 items and six subscales plus the total score were considered, and for which the total score ranks from 0 to 165. The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum I included patients whose FMR1 gene was fully methylated; Stratum II included patients whose FMR1 gene was partially methylated.

  11. Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I [ Time Frame: Baseline to week 12 ]
    The Repetitive Behavior Scale - Revised (RBS-R) is a rating tool that captures the breadth of repetitive behavior. It is a 43-item questionnaire filled by the caregivers. Each behavior assessed is rated from 0 (behavior does not occur) to 3 (behavior occurs and it is a severe problem). The total score ranks from 0 to 129. The behaviors are grouped into six domains: ritualistic behavior (range 0 to 18); sameness behavior (range 0 to 33); stereotypic behavior (range 0 to 18); self-injurious behavior (range 0 to 24); compulsive behavior (range 0 to 24); and restricted interests (range 0 to 12). A negative change represents improvement. Stratum I included patients whose FMR1 gene was fully methylated

  12. Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II [ Time Frame: Baseline to week 12 ]
    The Repetitive Behavior Scale - Revised (RBS-R) is a rating tool that captures the breadth of repetitive behavior. It is a 43-item questionnaire filled by the caregivers. Each behavior assessed is rated from 0 (behavior does not occur) to 3 (behavior occurs and it is a severe problem). The total score ranks from 0 to 129. The behaviors are grouped into six domains: ritualistic behavior (range 0 to 18); sameness behavior (range 0 to 33); stereotypic behavior (range 0 to 18); self-injurious behavior (range 0 to 24); compulsive behavior (range 0 to 24); and restricted interests (range 0 to 12). A negative change represents improvement. Stratum II included patients whose FMR1 gene was partially methylated



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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • Weigh less than 32 kg
  • Females who are sexually active

Other protocol-defined inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01357239


  Hide Study Locations
Locations
United States, California
Novartis Investigative Site
Sacramento, California, United States, 95817
United States, Georgia
Novartis Investigative Site
Decatur, Georgia, United States, 30033
United States, Illinois
Novartis Investigative Site
Chicago, Illinois, United States, 60612
United States, Massachusetts
Novartis Investigative Site
Boston, Massachusetts, United States, 02115
United States, Nebraska
Novartis Investigative Site
Omaha, Nebraska, United States, 68198-5575
United States, New York
Novartis Investigative Site
Staten Island, New York, United States, 10314
United States, Tennessee
Novartis Investigative Site
Nashville, Tennessee, United States, 37212
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030
Australia, New South Wales
Novartis Investigative Site
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Novartis Investigative Site
Parkville, Victoria, Australia, 3052
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1200
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Alberta
Novartis Investigative Site
Edmonton, Alberta, Canada, T6G 2E1
Canada, British Columbia
Novartis Investigative Site
Vancouver, British Columbia, Canada
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3T1C5
Denmark
Novartis Investigative Site
Glostrup, Denmark, 2600
France
Novartis Investigative Site
Bron, France, 69677
Novartis Investigative Site
Paris, France, 75013
Germany
Novartis Investigative Site
Dresden, Germany, 01307
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
München, Germany, 80639
Novartis Investigative Site
München, Germany, 81241
Novartis Investigative Site
Tübingen, Germany, 72076
Novartis Investigative Site
Würzburg, Germany, 97070
Indonesia
Novartis Investigative Site
Semarang, Jawa Tengah, Indonesia
Israel
Novartis Investigative Site
Ramat Gan, Israel, 52621
Italy
Novartis Investigative Site
Genova, GE, Italy, 16147
Novartis Investigative Site
Roma, RM, Italy, 00168
Novartis Investigative Site
Padova, Italy, 35128
Netherlands
Novartis Investigative Site
Rotterdam, Netherlands, 3015 CE
Spain
Novartis Investigative Site
Málaga, Andalucia, Spain, 29009
Novartis Investigative Site
Sabadell, Barcelona, Spain, 08208
Novartis Investigative Site
Sant Cugat, Cataluña, Spain, 08190
Sweden
Novartis Investigative Site
Spånga, Sweden, 16374
Switzerland
Novartis Investigative Site
Lausanne, Switzerland
Novartis Investigative Site
Zurich, Switzerland, 8091
Turkey
Novartis Investigative Site
Istanbul, Turkey, 34093
United Kingdom
Novartis Investigative Site
Edinburgh, United Kingdom, EH10 5HF
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01357239     History of Changes
Other Study ID Numbers: CAFQ056B2214
2010-022638-96 ( EudraCT Number )
First Posted: May 20, 2011    Key Record Dates
Results First Posted: May 12, 2015
Last Update Posted: May 12, 2015
Last Verified: May 2015

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Fragile X Syndrome
Martin-Bell Syndrome
Genetic Diseases
X-Linked
Escalante's syndrome

Additional relevant MeSH terms:
Syndrome
Fragile X Syndrome
Disease
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System