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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01253629
First received: December 2, 2010
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Fragile X Syndrome
Drug: AFQ056
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate AFQ056 in Adult Patients With Fragile X Syndrome

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change from baseline in behavioral symptoms of Fragile X Syndrome using the Aberrant Behavior Checklist - Community (ABC-C) Total score in Stratum I [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Change from baseline in behavioral symptoms of Fragile X Syndrome (FXS) using the ABC-C Total score in Stratum II [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Global improvement of symptoms in Fragile X using the Clinical Global Impression-Improvement (CGI-I) scale [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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")

  • Change from baseline in irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity, and inappropriate speech assessed by the individual subscales of the ABC-C scale [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    comprised of five subscales (irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity and inappropriate speech) plus the total score which ranks from 0 to 174

  • The proportion of patients with clinical response in the ABC-C total score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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

  • improvement of repetitive behavior as measured by changes in the RBS-R [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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


Enrollment: 175
Study Start Date: November 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 25 mg bid AFQ056
1 capsule of 25 mg and 1 capsule of placebo per intake
Drug: AFQ056
AFQ056, was provided as hard gelatin capsules, 25mg and 100 mg oral dosage strengths, identical in appearance were used
Experimental: 50 mg bid AFQ056
2 capsules of 25 mg per intake
Drug: AFQ056
AFQ056, was provided as hard gelatin capsules, 25mg and 100 mg oral dosage strengths, identical in appearance were used
Experimental: 100 mg bid AFQ056
1 capsule of 100 mg and 1 capsule of placebo per intake
Drug: AFQ056
AFQ056, was provided as hard gelatin capsules, 25mg and 100 mg oral dosage strengths, identical in appearance were used
Placebo Comparator: Placebo
2 capsules of placebo per intake
Drug: Placebo
Placebo medication identical in appearance to active medication was provided

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
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

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01253629

  Hide Study Locations
Locations
United States, Arizona
Novartis Investigative Site
Phoenix, Arizona, United States, 85006
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, Indiana
Novartis Investigative Site
Indianapolis, Indiana, United States, 46202
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, Pennsylvania
Novartis Investigative Site
Media, Pennsylvania, United States, 19063
United States, South Carolina
Novartis Investigative Site
Greenwood, South Carolina, United States, 29646
United States, Tennessee
Novartis Investigative Site
Nashville, Tennessee, United States, 37212
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77090
Australia, New South Wales
Novartis Investigative Site
Ryde, New South Wales, Australia, 2112
Novartis Investigative Site
Waratah, New South Wales, Australia, 2298
Australia, Victoria
Novartis Investigative Site
Caulfield, Victoria, Australia, 3161
Canada, Ontario
Novartis Investigative Site
Brampton, Ontario, Canada, L6Y 1M5
Canada, Quebec
Novartis Investigative Site
Sherbrooke, Quebec, Canada, J1H 5N4
Denmark
Novartis Investigative Site
Glostrup, Denmark, 2600
France
Novartis Investigative Site
Bron Cedex, France, 69677
Novartis Investigative Site
Paris, France, 75013
Germany
Novartis Investigative Site
Berlin, Germany, 12200
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
Tübingen, Germany, 72076
Novartis Investigative Site
Würzburg, Germany, 97070
Italy
Novartis Investigative Site
Genova, GE, Italy, 16147
Novartis Investigative Site
Roma, RM, Italy, 00168
Spain
Novartis Investigative Site
Málaga, Andalucia, Spain, 29009
Novartis Investigative Site
Sant Cugat, Cataluña, Spain, 08190
Switzerland
Novartis Investigative Site
Lausanne, Switzerland
Novartis Investigative Site
Zurich, Switzerland, 8091
United Kingdom
Novartis Investigative Site
Edinburgh, United Kingdom, EH10 5HF
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01253629     History of Changes
Other Study ID Numbers: CAFQ056A2212, 2009-013667-19
Study First Received: December 2, 2010
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: BfArM
Italy: Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Switzerland: Swissmedic
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Novartis:
Fragile X Syndrome
Martin-Bell Syndrome
Genetic Diseases
X-Linked

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

ClinicalTrials.gov processed this record on September 22, 2014