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Long-term, Safety and Tolerability Study of AFQ056 in Adolescent Patients With Fragile X Syndrome (Open-label)

Primary Purpose

Fragile X Syndrome

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AFQ056
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fragile X Syndrome focused on measuring Fragile X Syndrome, Martin-Bell Syndrome, Genetic Diseases, X-Linked, Escalante's syndrome

Eligibility Criteria

12 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Group 1 patients:
  • Must have completed study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age within one week of enrollment into the open-label study.
  • Has a caregiver or caregivers who spend, on average, at least 6 hours per day with the patient , who is willing to and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits.
  • Group 2 patients:
  • Must meet one of the following conditions:
  • Completed Study CAFQ056B2131
  • Completed Study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age but enrollment into the current study was delayed for more than a week.
  • Discontinued prematurely from Study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age due to intolerability of the dosage in the patient's assigned treatment group.
  • Has a caregiver or caregivers who spend, on average, at least 6 hours per day with the patient , who is willing to and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits.

Exclusion Criteria:

  • Discontinuation from Study CAFQ056B2214 or CAFQ056B2131 or another study of AFQ056 which included FXS patients below 18 years of age due to safety reasons
  • Female patients who are sexually active at any time during the study
  • Any advanced, severe or unstable disease
  • History and/or presence of schizophrenia, bipolar disease, psychosis, confusional states and/or repeated hallucinations as per DSM-IV criteria
  • History of suicidal behavior or considered a high suicidal risk
  • 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.)
  • History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether or not there is evidence of local recurrence or metastases
  • Patients who are using (or used within 6 weeks before baseline) digoxin or warfarin
  • 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 within 6 weeks of baseline

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AFQ056 Treatment

Arm Description

All patients will initiate treatment with AFQ056 at a starting dose of 25 mg b.i.d. The dose will be titrated from 25 mg b.i.d to 50 mg b.i.d., 75 mg b.i.d. and 100 mg b.i.d. at weekly intervals. Dose adjustments (up- and down-titrations) will be permitted as needed to manage any tolerability issues and to ensure that patients reach their highest tolerated dose, not to exceed 100 mg b.i.d.

Outcomes

Primary Outcome Measures

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 participants 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 participants 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.

Secondary Outcome Measures

Full Information

First Posted
August 31, 2011
Last Updated
February 24, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01433354
Brief Title
Long-term, Safety and Tolerability Study of AFQ056 in Adolescent Patients With Fragile X Syndrome (Open-label)
Official Title
An Open-label Study to Evaluate the Long-term Safety and Tolerability of AFQ056 in Adolescent Patients With Fragile X Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Terminated
Why Stopped
The study treatment failed to demonstrate efficacy in target population in two other clinical studies (CAFQ056B2214 and CAFQ056A2212).
Study Start Date
November 2011 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to generate long-term safety, tolerability and efficacy data for AFQ056 in eligible adolescent patients with FXS who have participated in the CAFQ056B2214 study, the PK study CAFQ056B2131, or another study of AFQ056 which included FXS patients below 18 years of age provided the patient is at least 12 years of age at the time of entry into the current study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fragile X Syndrome
Keywords
Fragile X Syndrome, Martin-Bell Syndrome, Genetic Diseases, X-Linked, Escalante's syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
119 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AFQ056 Treatment
Arm Type
Experimental
Arm Description
All patients will initiate treatment with AFQ056 at a starting dose of 25 mg b.i.d. The dose will be titrated from 25 mg b.i.d to 50 mg b.i.d., 75 mg b.i.d. and 100 mg b.i.d. at weekly intervals. Dose adjustments (up- and down-titrations) will be permitted as needed to manage any tolerability issues and to ensure that patients reach their highest tolerated dose, not to exceed 100 mg b.i.d.
Intervention Type
Drug
Intervention Name(s)
AFQ056
Intervention Description
The investigational drug, AFQ056, will be provided as hard gelatin capsules. Two different oral dosage strengths,25mg and 100 mg, identical in appearance, will be used.
Primary Outcome Measure Information:
Title
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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 participants 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 participants 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.
Time Frame
Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Group 1 patients: Must have completed study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age within one week of enrollment into the open-label study. Has a caregiver or caregivers who spend, on average, at least 6 hours per day with the patient , who is willing to and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits. Group 2 patients: Must meet one of the following conditions: Completed Study CAFQ056B2131 Completed Study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age but enrollment into the current study was delayed for more than a week. Discontinued prematurely from Study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age due to intolerability of the dosage in the patient's assigned treatment group. Has a caregiver or caregivers who spend, on average, at least 6 hours per day with the patient , who is willing to and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits. Exclusion Criteria: Discontinuation from Study CAFQ056B2214 or CAFQ056B2131 or another study of AFQ056 which included FXS patients below 18 years of age due to safety reasons Female patients who are sexually active at any time during the study Any advanced, severe or unstable disease History and/or presence of schizophrenia, bipolar disease, psychosis, confusional states and/or repeated hallucinations as per DSM-IV criteria History of suicidal behavior or considered a high suicidal risk 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.) History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether or not there is evidence of local recurrence or metastases Patients who are using (or used within 6 weeks before baseline) digoxin or warfarin 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 within 6 weeks of baseline Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Novartis Investigative Site
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Novartis Investigative Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Novartis Investigative Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-5575
Country
United States
Facility Name
Novartis Investigative Site
City
Staten Island
State/Province
New York
ZIP/Postal Code
10314
Country
United States
Facility Name
Novartis Investigative Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
Novartis Investigative Site
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Novartis Investigative Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Glostrup
ZIP/Postal Code
2600
Country
Denmark
Facility Name
Novartis Investigative Site
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Novartis Investigative Site
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Novartis Investigative Site
City
München
ZIP/Postal Code
80639
Country
Germany
Facility Name
Novartis Investigative Site
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Novartis Investigative Site
City
Würzburg
ZIP/Postal Code
97070
Country
Germany
Facility Name
Novartis Investigative Site
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16147
Country
Italy
Facility Name
Novartis Investigative Site
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Novartis Investigative Site
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Málaga
State/Province
Andalucia
ZIP/Postal Code
29009
Country
Spain
Facility Name
Novartis Investigative Site
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
Novartis Investigative Site
City
Sant Cugat
State/Province
Cataluña
ZIP/Postal Code
08190
Country
Spain
Facility Name
Novartis Investigative Site
City
Spånga
ZIP/Postal Code
16374
Country
Sweden
Facility Name
Novartis Investigative Site
City
Lausanne
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Edinburgh
ZIP/Postal Code
EH10 5HF
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
26855682
Citation
Bailey DB Jr, Berry-Kravis E, Wheeler A, Raspa M, Merrien F, Ricart J, Koumaras B, Rosenkranz G, Tomlinson M, von Raison F, Apostol G. Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study. J Neurodev Disord. 2016;8:1. doi: 10.1186/s11689-015-9134-5. Epub 2015 Dec 15.
Results Reference
derived

Learn more about this trial

Long-term, Safety and Tolerability Study of AFQ056 in Adolescent Patients With Fragile X Syndrome (Open-label)

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