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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01357239




Registration number
NCT01357239
Ethics application status
Date submitted
18/05/2011
Date registered
20/05/2011
Date last updated
12/05/2015

Titles & IDs
Public title
Safety and Efficacy of AFQ056 in Adolescent Patients With Fragile X Syndrome
Scientific 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
Secondary ID [1] 0 0
2010-022638-96
Secondary ID [2] 0 0
CAFQ056B2214
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fragile X Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Mental Health 0 0 0 0
Learning disabilities
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AFQ056
Treatment: Drugs - Placebo

Experimental: 25 mg bid -

Experimental: 50 mg bid -

Experimental: 100 mg bid -

Placebo Comparator: Placebo -


Treatment: Drugs: AFQ056


Treatment: Drugs: Placebo


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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 - 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
Timepoint [1] 0 0
Baseline to week 12
Secondary outcome [1] 0 0
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 - 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
Timepoint [1] 0 0
Baseline to week 12
Secondary outcome [2] 0 0
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) - 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
Timepoint [2] 0 0
Baseline to week 12
Secondary outcome [3] 0 0
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum I Patients - 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.
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum II Patients - 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
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I - 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.
Timepoint [5] 0 0
12 weeks
Secondary outcome [6] 0 0
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II - 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
Timepoint [6] 0 0
12 weeks
Secondary outcome [7] 0 0
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 - 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
Timepoint [7] 0 0
Baseline to week 12
Secondary outcome [8] 0 0
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 - 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
Timepoint [8] 0 0
Baseline to week 12
Secondary outcome [9] 0 0
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 - 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.
Timepoint [9] 0 0
12 weeks
Secondary outcome [10] 0 0
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 - 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.
Timepoint [10] 0 0
12 weeks
Secondary outcome [11] 0 0
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I - 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
Timepoint [11] 0 0
Baseline to week 12
Secondary outcome [12] 0 0
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II - 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
Timepoint [12] 0 0
Baseline to week 12

Eligibility
Key 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
Minimum age
12 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Belgium
State/province [9] 0 0
Bruxelles
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Canada
State/province [11] 0 0
Alberta
Country [12] 0 0
Canada
State/province [12] 0 0
British Columbia
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Denmark
State/province [14] 0 0
Glostrup
Country [15] 0 0
France
State/province [15] 0 0
Bron
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
Germany
State/province [17] 0 0
Dresden
Country [18] 0 0
Germany
State/province [18] 0 0
Mainz
Country [19] 0 0
Germany
State/province [19] 0 0
München
Country [20] 0 0
Germany
State/province [20] 0 0
Tübingen
Country [21] 0 0
Germany
State/province [21] 0 0
Würzburg
Country [22] 0 0
Indonesia
State/province [22] 0 0
Jawa Tengah
Country [23] 0 0
Israel
State/province [23] 0 0
Ramat Gan
Country [24] 0 0
Italy
State/province [24] 0 0
GE
Country [25] 0 0
Italy
State/province [25] 0 0
RM
Country [26] 0 0
Italy
State/province [26] 0 0
Padova
Country [27] 0 0
Netherlands
State/province [27] 0 0
Rotterdam
Country [28] 0 0
Spain
State/province [28] 0 0
Andalucia
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Cataluña
Country [31] 0 0
Sweden
State/province [31] 0 0
Spånga
Country [32] 0 0
Switzerland
State/province [32] 0 0
Lausanne
Country [33] 0 0
Switzerland
State/province [33] 0 0
Zurich
Country [34] 0 0
Turkey
State/province [34] 0 0
Istanbul
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Edinburgh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01357239
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications