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 |
FXS is a genetic condition caused by a change in the FMR1 gene. A defect in this gene causes your body to produce too little or none of a protein that is needed for normal brain development. |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025463 |
E.1.2 | Term | Major depressive disorder, single episode |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the efficacy of 12-week treatment with RO4917523 in patients with Fragile X Syndrome (FXS) as measured by the ADAMS total score
• To evaluate the safety and tolerability of 12-week treatment with RO4917523 in patients with FXS
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E.2.2 | Secondary objectives of the trial |
• Change from baseline in symptoms as measured by the: Aberrant Behaviour Checklist (ABC) total, ABC factor scores, Anxiety Depression and Mood Scale (ADAMS) total, ADAMS factor scores, and Social Responsiveness Scale (SRS)
• Change from baseline in cognitive function as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
• Clinical Global Impression-Improvement (CGI-I) and change from baseline in the Clinical Global Impression-Severity (CGI-S)
• Clinical response (at least 25% improvement in the ABC total score and a CGI-I score of 1 or 2)
• Change in the caregiver-identified most troubling symptom as measured by the Visual Analogue Scale (VAS)
• Change from baseline in adaptive behaviour skills as measured by the Vineland Adaptive Behavior Scale (VABS-II)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adults and adolescents (14 to 50)
• CGI-S of 3 (mildly ill) or more
• ABC total score of 20 or more
• Diagnosis of FXS with a confirmed FMR1 full mutation
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E.4 | Principal exclusion criteria |
• Have previously received treatment with another mGlu5 receptor antagonist within 18 months or RO4917523
• Enrollment/participation in any interventional study (clinical trial) involving an investigational drug (unapproved) or non-drug treatment within the prior 3 months or 5 times the half-life (whichever is longer)
• Any uncontrolled, unstable clinically significant psychiatric condition other than FXS that may interfere with interpretation of safety and efficacy evaluations (e.g. Attention Deficit Hyperactivity Disorder (ADHD))
• Current symptoms or presumption of psychosis or euphoria, history of catatonia, hallucinations or delusional thoughts
• History of suicidal behaviour or otherwise considered a high suicidal risk by the investigator |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the ADAMS total score from baseline to end of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from baseline to end of treatment (12 weeks) |
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E.5.2 | Secondary end point(s) |
• Change from baseline in symptoms as measured by the ABC and ADAMS (total and factor scores), and the SRS
• Change from baseline in cognitive function as measured by the RBANS
• CGI-I and change from baseline in the CGI-S
• Clinical response (at least 25% improvement in the ABC total score and a CGI-I score of 1 or 2)
• Change in the caregiver-identified most troubling symptom as measured by the VAS
• Change from baseline in adaptive behavior skills as measured by the VABS-II
• To investigate the pharmacokinetics and exposure response relationship of RO4917523 in patients with FXS using a population analysis approach.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from baseline to end of treatment (12 weeks) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 |
Patient Reported Outcomes, Psychometric testing of assessment scales for use in FXS |
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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 | 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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Argentina |
Canada |
Chile |
France |
Mexico |
Peru |
Spain |
Sweden |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |