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

• ClinicalTrials.gov Identifier: NCT01348087
• Recruitment Status: Terminated
• First Posted: May 5, 2011
• Results First Posted: May 25, 2016
• Last Update Posted: May 25, 2016
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Fragile X Syndrome	Drug: AFQ056	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 148 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: August 2011
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: September 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: CAFQ056B2279; 2011-001952-12 ( EudraCT Number )
• First Posted: May 5, 2011
• Results First Posted: May 25, 2016
• Last Update Posted: May 25, 2016
• Last Verified: April 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Fragile X Syndrome; Martin-Bell Syndrome; Genetic Diseases; X-Linked; Escalante's syndrome

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