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

NCT01348087 | Terminated Phase 2 Results DMC

• 2 other identifiers: CAFQ056B22792011-001952-12
• Study Type: interventional
• Target: 148
• Locations: 10 countries
• Sites: 28

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).

Conditions

Fragile X Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

AFQ056 100 mg (Bid)

EXPERIMENTAL

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

Interventions

AFQ056 DRUG

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

AFQ056 100 mg (Bid)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (28)

Novartis Investigative Site

Phoenix, Arizona, 85006, United States

Location

Novartis Investigative Site

Sacramento, California, 95817, United States

Location

Novartis Investigative Site

Decatur, Georgia, 30033, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60612, United States

Location

Novartis Investigative Site

Indianapolis, Indiana, 46202, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02115, United States

Location

Novartis Investigative Site

Omaha, Nebraska, 68198-5575, United States

Location

Novartis Investigative Site

Staten Island, New York, 10314, United States

Location

Novartis Investigative Site

Media, Pennsylvania, 19063, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37212, United States

Location

Novartis Investigative Site

Ryde, New South Wales, 2112, Australia

Location

Novartis Investigative Site

Waratah, New South Wales, 2298, Australia

Location

Novartis Investigative Site

Caulfield, Victoria, 3161, Australia

Location

Novartis Investigative Site

Brampton, Ontario, L6Y 1M5, Canada

Location

Novartis Investigative Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Novartis Investigative Site

Glostrup Municipality, 2600, Denmark

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Paris, 75013, France

Location

Novartis Investigative Site

Berlin, Germany, 12203, Germany

Location

Novartis Investigative Site

Mainz, Germany, 55131, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Würzburg, 97070, Germany

Location

Novartis Investigative Site

Genova, GE, 16147, Italy

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Sant Cugat del Vallès, Catalonia, 08190, Spain

Location

Novartis Investigative Site

Lausanne, 1011, Switzerland

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

Novartis Investigative Site

Edinburgh, EH10 5HF, United Kingdom

Location

MeSH Terms

Conditions

Fragile X Syndrome; Genetic Diseases, Inborn

Interventions

mavoglurant

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Limitations and Caveats

The sponsor decided to terminate this study prematurely, as the study treatment failed to demonstrate efficacy in target population in two other clinical studies: CAFQ056B2214 (NCT01357239) and CAFQ056A2212 (NCT01253629).

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2011
• First Posted: May 5, 2011
• Study Start: August 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: May 25, 2016
• Results First Posted: May 25, 2016

Record last verified: 2016-04

Locations

US (10); FR (2); CH (2); GB (1); CA (2); ES (2); IT (1); DE (4); DK (1); AU (3)