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

This study has been terminated.
(Study treatment AFQ056 failed to demonstrate efficacy in the adult patient with Fragile X Syndrome in 2 other clinical studies (CAFQ056B2214 and CAFQ056A2212))
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01348087
First received: May 3, 2011
Last updated: April 11, 2016
Last verified: April 2016
  Purpose
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).

Condition Intervention Phase
Fragile X Syndrome
Drug: AFQ056
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Study to Evaluate the Long-term Safety, Tolerability and Efficacy of AFQ056 in Adult Patients With Fragile X Syndrome

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs). [ Time Frame: Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial ] [ Designated as safety issue: Yes ]
    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


Enrollment: 148
Study Start Date: August 2011
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01348087

  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, Tennessee
Novartis Investigative Site
Nashville, Tennessee, United States, 37212
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, 12203
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
Spain
Novartis Investigative Site
Malaga, Andalucia, Spain, 29010
Novartis Investigative Site
Sant Cugat, Catalunya, Spain, 08190
Switzerland
Novartis Investigative Site
Lausanne, Switzerland, 1011
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

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01348087     History of Changes
Other Study ID Numbers: CAFQ056B2279  2011-001952-12 
Study First Received: May 3, 2011
Results First Received: September 9, 2015
Last Updated: April 11, 2016
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: National Health and Medical Research Council
Switzerland: Swissmedic
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Novartis:
Fragile X Syndrome
Martin-Bell Syndrome
Genetic Diseases
X-Linked
Escalante's syndrome

Additional relevant MeSH terms:
Syndrome
Fragile X 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

ClinicalTrials.gov processed this record on August 30, 2016