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

• ClinicalTrials.gov Identifier: NCT01253629
• Recruitment Status: Completed
• First Posted: December 3, 2010
• Last Update Posted: April 25, 2016
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 175 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 AFQ056 in Adult Patients With Fragile X Syndrome
• Study Start Date: November 2010
• Actual Primary Completion Date: August 2013
• Actual Study Completion Date: August 2013

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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 :

1. Change from baseline in behavioral symptoms of Fragile X Syndrome (FXS) using the ABC-C Total score in Stratum II [ Time Frame: 12 weeks ]
   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.
2. Global improvement of symptoms in Fragile X using the Clinical Global Impression-Improvement (CGI-I) scale [ Time Frame: 12 weeks ]
   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")
3. 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 ]
   comprised of five subscales (irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity and inappropriate speech) plus the total score which ranks from 0 to 174
4. The proportion of patients with clinical response in the ABC-C total score [ Time Frame: 12 weeks ]
   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
5. improvement of repetitive behavior as measured by changes in the RBS-R [ Time Frame: Week 12 ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• 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

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

  Show 31 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Berry-Kravis E, Des Portes V, Hagerman R, Jacquemont S, Charles P, Visootsak J, Brinkman M, Rerat K, Koumaras B, Zhu L, Barth GM, Jaecklin T, Apostol G, von Raison F. Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. Sci Transl Med. 2016 Jan 13;8(321):321ra5. doi: 10.1126/scitranslmed.aab4109.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01253629 History of Changes
• Other Study ID Numbers: CAFQ056A2212; 2009-013667-19 ( EudraCT Number )
• First Posted: December 3, 2010
• Last Update Posted: April 25, 2016
• Last Verified: March 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Fragile X Syndrome; Martin-Bell Syndrome; Genetic Diseases; X-Linked

Additional relevant MeSH terms:

Fragile X Syndrome; 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