Long-term, Safety, Tolerability and Efficacy Study of AFQ056 in Adult Patients With Fragile X Syndrome

An Open-label Study to Evaluate the Long-term Safety, Tolerability and Efficacy of AFQ056 in Adult Patients With Fragile X Syndrome

The purpose of this study is to generate long-term safety, tolerability and efficacy data for AFQ056 in eligible adult patients with FXS who have participated in the CAFQ056A2212 (NCT01253629).study and patients who have participated in the previous proof-of-concept study CAFQ056A2204 (NCT00718341).

Study Overview

• Status: Terminated
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: AFQ056

Detailed Description

A 148 patients were enrolled into this treatment extension trial conducted for at least 3 years. This extension trial was terminated after the decision to terminate the AFQ056 development program. The decision was based on the results of two randomized, double blind, placebo controlled phase IIb trials in adult and adolescent FXS patients (CAFQ056A2212 and CAFQ056B2214respectivly), both of which failed to demonstrate efficacy in the FXS population. As this extension trial was terminated, only the primary objective and safety are represented.

• Study Type: Interventional
• Enrollment (Actual): 148
• 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, 12203
    • 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
• Spain
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Catalunya
    • Sant Cugat, Catalunya, Spain, 08190
      • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland, 1011
    • 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
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria Group 1 patients

• Had to have completed the CAFQ056A2212 study or another study of AFQ056 which included adult FXS patients within one week of enrollment into the open-label study.
• Females of child-bearing potential had to follow protocol requirements with respect to contraception.
• Have a caregiver or caregivers who spent, on average, at least six hours per day with the patient, who were willing and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits.

Group 2:

• Had to have:
• Completed Study CAFQ056A2204.
• Completed Study CAFQ056A2212 or another study of AFQ056 which included adult patients with FXS but enrollment into the current study was delayed for more than a week.
• Discontinued prematurely from Study CAFQ056A2212 or another study of AFQ056 which included adult patients with FXS due to intolerability of the dosage in the patient's assigned treatment group.
• Females of child-bearing potential had to follow protocol requirements with respect to contraception.
• Have a caregiver or caregivers who spent, on average, at least six hours per day with the patient, who were willing and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits

Exclusion criteria

Any advanced, severe or unstable disease

• History of severe self- injurious behavior
• History of uncontrolled seizure disorder or resistant to therapy within the past 2 years (Patients who are clinically stable under anti-convulsant therapy for the past 2 years are not excluded)
• History of clinically significant allergies requiring hospitalization or non- inhaled corticosteroid therapy (asthma, anaphylaxis, etc.)
• Using (or used within 6 weeks before baseline) concomitant medications that are potent inhibitors or inducers of CYP3A4
• Using glutamatergic agents (riluzole, memantine, etc.) or lithium, digoxin, or warfarin within 6 weeks of baseline Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: AFQ056 100 mg (Bid); All patients initiated treatment with AFQ056 at a starting dose of 25 milligram (mg) twice daily. The dose was titrated from 25mg bid to 50mg bid, 75mg bid and 100mg bid at weekly intervals. Dose adjustments (up- and down titrations) were permitted as needed to manage any tolerability issues and to ensure that patients reach their highest tolerated dose not to exceed 100mg bid.

Drug: AFQ056; The investigational drug, AFQ056, will be provided as hard gelatin capsules. Two different oral dosage strengths, identical in appearance, will be used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).	Adverse events were summarized for the open-label treatment period, where the open-label treatment period is defined based on how AEs were collected and reported according to the manner in which patients entered the current study and which treatment (AFQ056 or placebo) they were receiving in the previous study. AEs which were continuing from the core study or that started after the end of core study but prior to first dose of open-label study medication in the extension study for Category 1 patients are shown under ('Prior to Ext. first dose'). AEs which started during the open-label treatment period are presented based on the last AFQ056 dose taken on or before the onset date of the AE (25 mg bid; 50 mg bid; 75 mg bid; or 100 mg bid). No efficacy data presented as study was terminated	Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: May 3, 2011
• First Submitted That Met QC Criteria: May 4, 2011
• First Posted (Estimate): May 5, 2011

Study Record Updates

• Last Update Posted (Estimate): May 25, 2016
• Last Update Submitted That Met QC Criteria: April 11, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Fragile X Syndrome; Martin-Bell Syndrome; Genetic Diseases; X-Linked; Escalante's syndrome
• 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: CAFQ056B2279; 2011-001952-12 (EudraCT Number)