Safety and Efficacy of AFQ056 in Adolescent Patients With Fragile X Syndrome

NCT01357239 | Completed Phase 2 Results

• 2 other identifiers: CAFQ056B22142010-022638-96
• Study Type: interventional
• Target: 139
• Locations: 16 countries
• Sites: 38

Brief Summary

This Phase IIb study is designed to assess whether 3 doses of AFQ056 are safe and effective in treating the behavioral symptoms of Fragile X Syndrome.

Conditions

Fragile X Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the Aberrant Behavior Checklist-Community Edition (ABC-CFX) Total Score in Stratum I Patients Exposed to AFQ056 100 mg Bid

  The Aberrant Behavior Checklist-Community edition (ABC-C) is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales (irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity, inappropriate speech and social avoidance) plus the total score were considered, and for which the total score ranks from 0 to 165. Stratum I included patients whose Fragile X Mental Retardation 1 (FMR1) gene was fully methylated

  Baseline to week 12

Secondary Outcomes (12)

• Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the ABC-CFX Total Score in Stratum II Patients Exposed to All 3 Doses of AFQ056

  Baseline to week 12

• Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the ABC-CFX Total Score in Stratum I Patients Exposed to the Two Lower Doses of AFQ056 (25 mg Bid and 50 mg Bid)

  Baseline to week 12

• Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum I Patients

  12 weeks

• Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum II Patients

  12 weeks

• Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I

  12 weeks

Study Arms (4)

25 mg bid

EXPERIMENTAL

Drug: AFQ056

50 mg bid

EXPERIMENTAL

Drug: AFQ056

100 mg bid

EXPERIMENTAL

Drug: AFQ056

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

AFQ056 DRUG

100 mg bid; 25 mg bid; 50 mg bid

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients with Fragile X Syndrome, who are at least moderately ill based on a Clinical Global Impression Severity score of at least 4 and have qualifying scores on the ABC-C and IQ test at Visit 1

You may not qualify if:

• Advanced, severe or unstable disease that may interfere with the study outcome evaluations
• Cancer within the past 5 years, other than localized skin cancer
• Current treatment with more than two psychoactive medications, excluding anti-epileptics
• History of severe self-injurious behavior
• Weigh less than 32 kg
• Females who are sexually active

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (38)

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

Houston, Texas, 77030, 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

Edmonton, Alberta, T6G 2E1, Canada

Location

Novartis Investigative Site

Vancouver, British Columbia, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T1C5, 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

Mainz, Germany, 55131, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

München, 80639, Germany

Location

Novartis Investigative Site

München, 81241, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Würzburg, 97070, Germany

Location

Novartis Investigative Site

Semarang, Central Java, Indonesia

Location

Novartis Investigative Site

Ramat Gan, 52621, Israel

Location

Novartis Investigative Site

Genova, GE, 16147, Italy

Location

Novartis Investigative Site

Roma, RM, 00168, 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

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Edinburgh, EH10 5HF, United Kingdom

Location

Related Publications (2)

• 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

• Berry-Kravis E, Des Portes V, Hagerman R, Jacquemont S, Charles P, Visootsak J, Brinkman M, Rerat K, Koumaras B, Zhu L, Barth GM, Jaecklin T, Apostol G, von Raison F. Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. Sci Transl Med. 2016 Jan 13;8(321):321ra5. doi: 10.1126/scitranslmed.aab4109.

  PMID: 26764156 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

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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2011
• First Posted: May 20, 2011
• Study Start: May 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: May 12, 2015
• Results First Posted: May 12, 2015

Record last verified: 2015-05

Locations

US (8); ID (1); AU (2); NL (1); SE (1); GB (1); DE (6); CA (3); IT (3); ES (3); TU (1); DK (1); BE (2); IL (1); CH (2); FR (2)