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

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate AFQ056 in Adult Patients With Fragile X Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: AFQ056; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Ryde, New South Wales, Australia, 2112
      • Novartis Investigative Site
    • Waratah, New South Wales, Australia, 2298
      • Novartis Investigative Site
  • Victoria
    • Caulfield, Victoria, Australia, 3161
      • Novartis Investigative Site
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6Y 1M5
      • Novartis Investigative Site
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Novartis Investigative Site
• Denmark
  • Glostrup, Denmark, 2600
    • Novartis Investigative Site
• France
  • Bron Cedex, France, 69677
    • Novartis Investigative Site
  • Paris, France, 75013
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 12200
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
  • Würzburg, Germany, 97070
    • Novartis Investigative Site
• Italy
  • GE
    • Genova, GE, Italy, 16147
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
• Spain
  • Andalucia
    • Málaga, Andalucia, Spain, 29009
      • Novartis Investigative Site
  • Cataluña
    • Sant Cugat, Cataluña, Spain, 08190
      • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland
    • Novartis Investigative Site
  • Zurich, Switzerland, 8091
    • Novartis Investigative Site
• United Kingdom
  • Edinburgh, United Kingdom, EH10 5HF
    • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Novartis Investigative Site
  • California
    • Sacramento, California, United States, 95817
      • Novartis Investigative Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Novartis Investigative Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5575
      • Novartis Investigative Site
  • New York
    • Staten Island, New York, United States, 10314
      • Novartis Investigative Site
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Novartis Investigative Site
  • South Carolina
    • Greenwood, South Carolina, United States, 29646
      • Novartis Investigative Site
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Novartis Investigative Site
  • Texas
    • Houston, Texas, United States, 77090
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in behavioral symptoms of Fragile X Syndrome using the Aberrant Behavior Checklist - Community (ABC-C) Total score in Stratum I	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)	12 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

• Results for CAFQ056A2212 from the Novartis Clinical Trial website

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: December 2, 2010
• First Submitted That Met QC Criteria: December 2, 2010
• First Posted (ESTIMATE): December 3, 2010

Study Record Updates

• Last Update Posted (ACTUAL): December 23, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Fragile X Syndrome; Martin-Bell Syndrome; Genetic Diseases; X-Linked
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Fragile X Syndrome
• Other Study ID Numbers: CAFQ056A2212; 2009-013667-19 (EUDRACT_NUMBER)