Fragile X syndrome MedDRA version: 14.1 Level: PT Classification code 10017324 Term: Fragile X syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Group 1 patients: • Must have completed the 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 who spends, 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. • Male or female, between 12 and 17 years of age, inclusive at the time of inclusion in the CAFQ056B2214 study or at least 12 years of age at the time of entry into the current study when the patient participated in another study of AFQ056 which included FXS patients below 18 years of age; • Have a caregiver or caregivers who are willing 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: o completed Study CAFQ056B2131 o 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 o 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 who spends, 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 • The caregiver/legally acceptable representative must be able to communicate well with the investigator and must understand and support the study requirements by providing written informed consent. • Where possible the patient should also provide his or her written assent Other protocol-defined inclusion criteria may apply • Male or female, between 12 and 17 years of age, inclusive, at the time of inclusion in Study CAFQ056B2214, or between 12 and 18 years of age, inclusive, at the time of inclusion in Study CAFQ056B2131, or at least 12 years of age at the time of entry into the current study when the patient particiapted in another study of AFQ056 which included FXS patients below 18 years of age • Have a caregiver or caregivers who are willing and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits Are the trial subjects under 18? yes Number of subjects for this age range: 160 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Discontinuation from CAFQ056B2214 or CAFQ056B2131 or another study at AFQ056 which included FXS patients below 18 years of age due to safety reasons 2) Female patients who are sexually active at any time during the study 3) Any advanced, severe or unstable disease 4) Past medical history of clinically significant ECG abnormalities or QTcF > 450 msec for males and > 470 msec for females during the screening period (Group 2 patients) or at the end of study visit in the previous study for Group 1 patients 5) Lab screening values that AST, ALT, GGT, total bilirubin or creatinine > 1.5 X ULN (upper limit of normal) for the central laboratory 6) History of major surgery or major medical event that requires hospitalization or major surgery within the past 6 months, unless the patient recovered fully or is considered clinially stable by the study physician 7) Donated or lost more than 2.4 mL of blood per kg of body weight within (4) weeks prior to screening (V1) or longer if required by local regulation 8) History and/or presence of schizophrenia, bipolar disease, psychosis, confusional states and/or repeated hallucinations as per DSM-IV criteria 9) History of suicidal behavior or considered a high suicidal risk 10) History of severe self-injurious behavior 11) 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) 12) History of clinically significant allergies requiring hospitalization or non-inhaled corticosteroid therapy (asthma, anaphylaxis, etc.) 13) 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 14) Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG serum pregnancy test 15) Using (or used within 6 weeks before randiomization) concomitant medications that are potent inhibitors or inducers or CYP3A4. In addition, patients are to avoid drinking grapefruit juice during the study 16) patients who are using (or used within 6 weeks before baseline) digoxin or warfarin 17) Using glutamatergic agents (riluzole, memantine, etc.) or lithium within 6 weeks of baseline 18) Use of investigational drugs (other that AFQ056) at the time of enrollment, or within 6 weeks or 5 half-lives of baseline, whichever is longer 19) Participation in any pharmacological clinical investigation (other than observational studies or those including AFQ056) within 6 weeks prior to baseline or longer if required by local regulation 20) Patients who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study or displaying abnormalities in safety assessments at baseline 21) Patients who are unable to swallow study medication in a capsule formulation Other pro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety and tolerability of AFQ056 in adolescent patients with FXS as assessed by: • Incidence and severity of adverse events and serious adverse events • Changes in vital signs, laboratory assessments, and ECGs • Monitoring the hypothalamic-pituitary-adrenal/thyroid axis function and childhood developmental milestones ; Secondary Objective: To evaluate the long-term efficacy of AFQ056 treatment in both FM (Fully Methylated) and PM (Partially Methylated) patients with FXS as assessed by: • Change from baseline in the Aberrant Behavior Checklist – Community edition (ABC-C) total score and subscale scores • Rating of global improvement of symptoms in Fragile X patients using the Clinical Global Impression - Improvement (CGI-I) scale. • Change from baseline in the Repetitive Behavior Scale – Revised (RBS-R) total score and subscale scores • Change from baseline in the Social Responsiveness Scale (SRS) total score • To collect pharmacokinetic data of AFQ056 in the target patient population ; Primary end point(s): 1) Number of patients having any adverse events (AE) by primary system organ class and preferred term during the 24 months of the study. Adverse events will be summarized by presenting the number of patients having any AE by primary system organ class and/or preferred term. 2) Changes in vital signs. Pulse and Blood pressure will be taken sitting after five minutes. Temperature will also be taken. 3) Changes in weight. Body weight (to the nearest 0.1 kilogram in indoor clothing, but without shoes) will be measured. 4) Changes in height. Height in centimeters (cm) will be measured. 5) Changes in standard lab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Change in the Aberrant Behavior Checklist-Community edition (ABC-C) The ABC-C is a symptom checklist for assessing problem behaviors of children and adults with intellectual disability. The ABC-C is comprised of 5 sub-scales (irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity and inappropriate speech) plus total score. The questionnaire is completed by the caregiver by attributing a score from 0 (“not a problem”) to 3 (“problem is severe in degree”) to each item of the questionnaire; the total score ranks from 0 to 174. Summary and change from baseline in the ABC-C total and subscale scores will be reported. 2) Change in the Clinical Global Impression Score – Severity/Improvement (CGI-S/I) scale. The CGI-I is used to assess treatment response in psychiatric patients. The scale is divided into two parts, one assessing the severity of illness (CGI-S) and one assessing the improvement (CGI-I). It is a clinician-rated scale. The CGI-I reports the global changes of the symptoms rated on a seven-point scale (from “very much improved” to “very much worse”). CGI-I will be summarized by visit. CGI-I will be evaluated using the extension study baseline visit as the reference visit. 3) Change in the Repetitive Behavior Scale – Revised (RBS-R). The RBS-R is a rating tool that captures the breadth of repetitive behavior: ritualistic behavior, sameness behavior, stereotypic behavior, self-injurious behavior, compulsive behavior, and restricted interests. Every behavior falling into one of the above categories is rated from 0 (behavior does not occur) to 3(behavior occurs and it is a severe problem). The total score ranks from 0 to 129. It is a questionnaire filled by the caregivers. 4) Change in the Social Responsiveness Scale (SRS) total score. The SRS distinguishes autism spectrum conditions from other p | — |
Countries
Australia, Belgium, Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactMedical Collaboration Centre
Novartis Pharmaceuticals UK Ltd
Outcome results
None listed