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

NCT01433354 | Terminated Phase 2 Results DMC

• 2 other identifiers: CAFQ056B22782011-002379-40
• Study Type: interventional
• Target: 119
• Locations: 13 countries
• Sites: 28

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.

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 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.

  Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial

Study Arms (1)

AFQ056 Treatment

EXPERIMENTAL

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.

Drug: AFQ056

Interventions

AFQ056 DRUG

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.

AFQ056 Treatment

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (28)

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

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

Nashville, Tennessee, 37212, United States

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Parkville, Victoria, 3052, Australia

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Glostrup Municipality, 2600, Denmark

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Mainz, Germany, 55131, Germany

Location

Novartis Investigative Site

München, 80639, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Würzburg, 97070, Germany

Location

Novartis Investigative Site

Ramat Gan, 52621, Israel

Location

Novartis Investigative Site

Genova, GE, 16147, Italy

Location

Novartis Investigative Site

Padua, 35128, Italy

Location

Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

Location

Novartis Investigative Site

Málaga, Andalusia, 29009, Spain

Location

Novartis Investigative Site

Sabadell, Barcelona, 08208, Spain

Location

Novartis Investigative Site

Sant Cugat del Vallès, Catalonia, 08190, Spain

Location

Novartis Investigative Site

Spånga, 16374, Sweden

Location

Novartis Investigative Site

Lausanne, Switzerland

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

Novartis Investigative Site

Edinburgh, EH10 5HF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26855682 DERIVED

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: August 31, 2011
• First Posted: September 13, 2011
• Study Start: November 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: March 24, 2016
• Results First Posted: October 12, 2015

Record last verified: 2016-02

Locations

GB (1); ES (3); US (7); IT (2); FR (1); SE (1); BE (2); DK (1); DE (4); IL (1); AU (2); NL (1); CH (2)