E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fragile X Syndrome |
Fragile X Syndrome |
|
E.1.1.1 | Medical condition in easily understood language |
Fragile X Syndrome |
Fragile X Syndrome |
|
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 | 15.0 |
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 |
|
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 assess the efficacy of AFQ056 100 mg BID versus placebo in reducing the ABC-C Total score (using the FXS-specific algorithm - ABC-CFX) after 12 weeks of treatment in FXS patients in Stratum I |
Um die Wirksamkeit von AFQ056 100 mg zwei mal täglich versus Placebo nach 12 Wochen Behandlung zu untersuchen. Hierzu wird die Reduzierung des ABC-C Total Scores (FXS-spezifische Algorythmus ABC-CFX) untersucht. |
|
E.2.2 | Secondary objectives of the trial |
Key secondary objective:
To assess the efficacy of three doses of AFQ056 versus placebo in reducing the ABC-CFX total score after 12 weeks of treatment in FXS patients with partially methylated (PM) FMR1 gene.
To assess the afficacy of two lower doses of AFQ056 (25 mg BID and 50 mg BID) versus placebo in reducing the ABC-CFX total score after 12 weeks of treatment in FXS patients with FMFMR1 gene. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 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
Other protocol-defined inclusion criteria may apply |
|
E.4 | Principal exclusion criteria |
• 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
Other protocol-defined exclusion criteria may apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in behavioral symptoms of Fragile X Syndrome using the Aberrant Behavior Checklist – Community (ABC-CFX) Total score in Stratum I |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Timeframe: 12 weeks
At multiple visits:
Visits 1, 2, 2.2, 3, 4, 5, 6 and 7 |
|
E.5.2 | Secondary end point(s) |
- Aberrant Behavour Checklist - Community Edition (ABC-CFX): Total score and subscales
- Clinical Global Impression - Improvement (CGI-I)
- Repetitive Behavior Scale - Revised (RBS-R)
- Safety and tolerability as measured by changes in vital signs, ECGs, laboratory values and percentages of adverse events and serious adverse events,
Neuropsychiatric Inventory - Questionnaire (NPI-Q) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Timeframe: 12 weeks for each secondary endpoint
- ABC-CFX: Visits 1, 2, 2.2, 3, 4, 5, 6 and 7
- CGI: Visits 4, 5, 6 and 7
- RBS-R: Visits 2, 3, 5 and 7
- Safety and tolerability: Timeframe 12 weeks
|
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 14 |
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 |
Israel |
Italy |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
|
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
|
Last visit of the last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 18 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 18 |