Fragile X Syndrome
Conditions
Keywords
Fragile X Syndrome, Martin-Bell Syndrome, Genetic Diseases, X-Linked, Escalante's syndrome
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.
Interventions
DRUGAFQ056
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial | 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. |
Countries
Australia, Belgium, Denmark, France, Germany, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 28 centres in 13 countries.
Pre-assignment details
A total of 120 patients were enrolled, of which 119 received the study medication. Category 1 patients received AFQ056 in the core study and enrolled in the extension within 7 days of the core study; Category 2 included all other patients who were enrolled into the extension study
Participants by arm
| Arm | Count |
|---|---|
| AFQ056 Participants from a previous AFQ056 study who entered the open-label extension study were administered AFQ056 capsules at a starting dose of 25 milligram (mg) twice daily (bid) and then titrated to 50 mg bid, 75 mg bid and 100 mg bid at weekly intervals. | 119 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative problems | 90 |
| Overall Study | Adverse Event | 6 |
| Overall Study | Lack of Efficacy | 17 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Subject Withdrew Consent | 3 |
Baseline characteristics
| Characteristic | AFQ056 |
|---|---|
| Age, Continuous | 15.2 years STANDARD_DEVIATION 1.75 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 31 | 23 / 119 | 30 / 118 | 33 / 116 | 74 / 108 | 103 / 119 |
| serious Total, serious adverse events | 0 / 31 | 0 / 119 | 1 / 118 | 0 / 116 | 3 / 108 | 4 / 119 |
Outcome results
Primary
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.
Time frame: Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial
Population: The analysis was performed in the safety set (SS) population, defined as participants who received at least one dose of study medication and had at least one safety assessment occurring after first dose of extension study medication. Here, 'Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AFQ056 | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one AE | 110 participants |
| AFQ056 | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to AEs | 6 participants |
| AFQ056 | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one severe AE | 8 participants |
| AFQ056 | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to non serious AE | 5 participants |
| AFQ056 | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any serious or significant AE | 4 participants |
| AFQ056 | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to SAEs | 1 participants |
| AFQ056 | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 4 participants |
| Prior to Ext. First Dose | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one severe AE | 0 participants |
| Prior to Ext. First Dose | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Prior to Ext. First Dose | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any serious or significant AE | 0 participants |
| Prior to Ext. First Dose | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to AEs | 1 participants |
| Prior to Ext. First Dose | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one AE | 10 participants |
| Prior to Ext. First Dose | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to non serious AE | 1 participants |
| Prior to Ext. First Dose | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to SAEs | 0 participants |
| AFQ056 25 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any serious or significant AE | 0 participants |
| AFQ056 25 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one severe AE | 1 participants |
| AFQ056 25 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one AE | 36 participants |
| AFQ056 25 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to AEs | 2 participants |
| AFQ056 25 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to SAEs | 0 participants |
| AFQ056 25 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| AFQ056 25 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to non serious AE | 2 participants |
| AFQ056 50 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 participants |
| AFQ056 50 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one AE | 41 participants |
| AFQ056 50 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one severe AE | 1 participants |
| AFQ056 50 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any serious or significant AE | 1 participants |
| AFQ056 50 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to AEs | 2 participants |
| AFQ056 50 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to SAEs | 0 participants |
| AFQ056 50 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to non serious AE | 2 participants |
| AFQ056 75 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any serious or significant AE | 0 participants |
| AFQ056 75 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one severe AE | 1 participants |
| AFQ056 75 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to non serious AE | 0 participants |
| AFQ056 75 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one AE | 44 participants |
| AFQ056 75 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to SAEs | 0 participants |
| AFQ056 75 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| AFQ056 75 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to AEs | 0 participants |
| AFQ056 100 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to non serious AE | 2 participants |
| AFQ056 100 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to AEs | 3 participants |
| AFQ056 100 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any serious or significant AE | 3 participants |
| AFQ056 100 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one severe AE | 5 participants |
| AFQ056 100 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued due to SAEs | 1 participants |
| AFQ056 100 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one AE | 90 participants |
| AFQ056 100 mg Bid | Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 participants |