Efficacy, Safety and Tolerability of AFQ056 in Fragile X Patients

A Multi-centre, Randomized, Double-blind, Placebo Controlled, Two-period, Crossover Proof-of-concept Study in Male Patients With Fragile X Syndrome to Assess the Efficacy, Safety and Tolerability of Multiple Oral Doses of AFQ056

This study will evaluate the safety, tolerability and efficacy of multiple doses of AFQ056 in patients with Fragile X Syndrome. The dose range will be 50 to 150 mg b.i.d. The primary read-out of efficacy is reduction in Aberrant-Behavior Checklist score.

Study Overview

• Status: Completed
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: AF056

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bron cedex, France, 69677
    • Novartis Investigator Site
• Italy
  • Rome, Italy, 00168
    • Novartis Investigator Site
• Switzerland
  • Lausanne, Switzerland, 1011
    • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male, non-smoking patients between 18 and 35 years of age (both inclusive).
• Patients with fmr1 full mutation (> 200 CGG repeats)
• Patients with a Clinical Global Impression Severity Score (CGI-S) of > 4 (moderately ill)
• Patients with a score of >20 in the ABC-C scale (at screening)
• Patients with a mental age of ≥ 48 months as measured by the Stanford-Binet test

Exclusion Criteria:

• Patients with DSM-IV diagnosis of schizophrenia, history and/or presence of psychosis, confusional states and/or repeated hallucinations.
• Patients with a history of seizures in the past 5 years without any therapeutic treatment controlling the disorders.
• Patients under stable anti-convulsant therapies that experienced seizures in the 2 years prior to randomization
• Patients with ECG abnormalities, autonomic dysfunctions, bronchospastic diseases, drug or atopic allergy
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs
• Patients using (or have used within four weeks before randomization) concomitant medications that are potent inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir, etc.)

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 2	Drug: Placebo
ACTIVE_COMPARATOR: 1	Drug: AF056

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Aberrant-Behavior Checklist- Community Edition

Secondary Outcome Measures

Outcome Measure
28 days treatment with AFQ056 on behavior (communication, socialization, daily living, repetitive behaviors, anxiety/avoidance, clinical global improvement)
28 days treatment with AFQ056 on cognition (receptive language, attention, vigilance…)

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ, Ramos FJ, Cornish K, He Y, Paulding C, Neri G, Chen F, Hadjikhani N, Martinet D, Meyer J, Beckmann JS, Delange K, Brun A, Bussy G, Gasparini F, Hilse T, Floesser A, Branson J, Bilbe G, Johns D, Gomez-Mancilla B. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med. 2011 Jan 5;3(64):64ra1. doi: 10.1126/scitranslmed.3001708.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): February 1, 2009

Study Registration Dates

• First Submitted: July 17, 2008
• First Submitted That Met QC Criteria: July 17, 2008
• First Posted (ESTIMATE): July 18, 2008

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 8, 2020
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: Fragile X Syndrome, adults, efficacy
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Fragile X Syndrome
• Other Study ID Numbers: CAFQ056A2204