E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017324 |
E.1.2 | Term | Fragile X syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of AFQ056 in adult patients with FXS as assessed by:
• Incidence and severity of adverse events and serious adverse events
• Changes in vital signs, laboratory assessments, and ECGs
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of AFQ056 treatment in both Fully Methylated and 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 Symptom – Research version (RBS) total score and subscale scores
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The study will be conducted in centers participating in studies CAFQ056A2212 or CAFQ056A2204 and other studies of AFQ056 which included adult patients with FXS.
Group 1 patients
1. Must have completed the CAFQ056A2212 study or another study of AFQ056 which included adult FXS patients within one week of enrollment into the open-label study.
2. Written informed consent must be obtained from the patient’s legally acceptable representative before any assessment is performed;
3. Male or female, at least 18 years of age at the time of screening in the previous study of AFQ056;
4. Have a caregiver or caregivers who spend(s), on average, at least six hours per day with the patient, who is/are willing and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits.
Group 2 patients
1. Must meet one of the following conditions:
a. completed Study CAFQ056A2204
b. completed Study CAFQ056A2212 or another study of AFQ056 which included adult patients with FXS but enrollment into the current study was delayed for more than a week
c. discontinued prematurely from Study CAFQ056A2212 or another study of AFQ056 which included adult patients with FXS due to intolerability of the dosage in the patient’s assigned treatment group (Patients who discontinue prematurely from their previous study due to intolerability of their assigned dose Other protocol-defined inclusion criteria may apply level may enter the current study, but at a date no sooner than their originallyscheduled completion of the prior study)
2. Written informed consent must be obtained from the patient’s legally acceptable representative before any assessment is performed;
3. Male or female, at least 18 years of age at the time of screening in the previous study of AFQ056
4. Have a caregiver or caregivers who spend(s), on average, at least six hours per day with
the patient, who is/are willing and capable of supervising treatment, providing input into
efficacy and safety assessments, and accompanying the patient to study visits.
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E.4 | Principal exclusion criteria |
1. Any advanced, severe or unstable disease
2. past medical history of clinically significant ECG abnormalities or QTcF > 450 msec for males and > 470 msec for females at screening (Group 2) or at the end of study visit in the previous trial for Group 1 patients
3. lab screening values that include AST, ALT, GGT, total bilirubin or creatinine ≥ 1.5 X ULN (upper limit of normal) for the central laboratory; total or unconjugated (indirect) bilirubin levels up to 3 X ULN for the central laboratory are allowed if the patient has a diagnosis of Gilbert’s syndrome;
4. 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 clinically stable;
5. history and/or presence of schizophrenia, bipolar disease, psychosis, confusional states and/or repeated hallucinations as per Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria;
6. history of suicidal behavior or considered a high suicidal risk;
7. History of severe self-injurious behavior
8. 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)
9. History of clinically significant allergies requiring hospitalization or non-inhaled corticosteroid therapy (asthma, anaphylaxis, etc.)
10. 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;
11. 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;
12. patients who are using (or used within 6 weeks before baseline) concomitant medications
that are potent inhibitors or inducers of CYP3A4 (e.g., ketoconazole, ritonavir, carbamazepine, etc.) (Refer to Appendix 2 for a list of medications). In addition, patients are to avoid drinking grapefruit juice during the study;
13. patients who are using (or used within 6 weeks before baseline) digoxin or warfarin; 14. patients using glutamatergic agents (riluzole, memantine, etc.) or lithium within 6 weeks of baseline (Refer to Appendix 2 for a list of medications);
15. use of investigational drugs (other than AFQ056) at the time of enrollment, or within 6 weeks or 5 half-lives of baseline, whichever is longer;
16. 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;
17. 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of the safety and tolerability of AFQ056 in adult patients with FXS as assessed by:
Incidence and severity of adverse events and serious adverse events and change in vital signs, laboratory assessments, and ECGs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At multiple visits:
weekly during first month and monthly afterwards
Time Frame: 9 months |
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E.5.2 | Secondary end point(s) |
- Aberrant Behavour Checklist - Community Edition (ABC-C): Total score and subscales
- Clinical Global Impression - Improvement (CGI-I) scale
- Repetitive Behaviour Symptom-Research version (RBS-R) - total score and subscale scores |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- ABC-C: Week 4, week 12, week 24, week 36
- CGI - I: Week 4, week 12, week 24, week 36
- RBS: Week 4, week 36
Time frame: 9 months for each |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Denmark |
France |
Germany |
Italy |
Spain |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |