Safety and Efficacy of AFQ056 in Adult Patients With Fragile X Syndrome - Full Text View

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:

Genetics Home Reference related topics: CASK-related intellectual disability fragile X syndrome MECP2 duplication syndrome PPM-X syndrome Renpenning syndrome tetrasomy 18p

MedlinePlus related topics: Fragile X Syndrome

Genetic and Rare Diseases Information Center resources: Fragile X Syndrome X-linked Mental Retardation and Macro-orchidism

U.S. FDA Resources

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

Show 31 Study Locations

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

ClinicalTrials.gov processed this record on March 02, 2015