E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017324 |
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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 |
Primary: To assess the efficacy of three doses of AFQ056 versus placebo in reducing the Aberrant Behavior Checklist – Community edition (ABC-C) Total score after 12 weeks of treatment in FXS patients with fully-methylated (FM) FMR1 gene. |
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E.2.2 | Secondary objectives of the trial |
Secondary: To assess the efficacy of three doses of AFQ056 versus placebo in reducing the ABC-C Total score after 12 weeks of treatment in FXS patients with partially-methylated (PM) FMR1 gene. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria • 18 and 45 years of age, inclusive • males and females; females must be following an acceptable method of birth control according to the protocol • previous diagnosis of FXS based upon documented genetic testing results (full mutation >200 CGG repeats). The diagnosis will need to be confirmed by genetic testing prior to the patient entering the Placebo Run-in Period • have a Clinical Global Impression Severity Score (CGI-S) of ≥ 4 (moderately ill) • have a score of > 20 in the ABC-C total scale • have a documented Intelligence Quotient (IQ) score lower than two standard deviations below the IQ test median • have a caregiver who spends, on average, at least six hours per day with the patient, who is willing and capable of supervising treatment, provInclusion criteria • 18 and 45 years of age, inclusive • males and females; females must be following an acceptable method of birth control according to the protocol • previous diagnosis of FXS based upon documented genetic testing results (full mutation >200 CGG repeats). The diagnosis will need to be confirmed by genetic testing prior to the patient entering the Placebo Run-in Period • have a Clinical Global Impression Severity Score (CGI-S) of ≥ 4 (moderately ill) • have a score of > 20 in the ABC-C total scale • have a documented Intelligence Quotient (IQ) score lower than two standard deviations below the IQ test median • have a caregiver who spends, on average, at least six hours per day with the patient, who is willing and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to all study visitsiding input into efficacy and safety assessments, and accompanying the patient to all study visits |
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E.4 | Principal exclusion criteria |
Exclusion criteria • 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 (Diagnostic and Statistical Manual of Mental Disorders) 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 • any treatment regimen, including psychotropic and/or anticonvulsant therapy that has not been stable for ≥ 6 weeks prior to randomization • current treatment with more than two psychoactive medications, excluding medication used specifically for seizure control • using (or used within 6 weeks before randomization) concomitant medications that are potent inhibitors or inducers of CYP3A4 • using glutamatergic agents (riluzole, memantine, etc.) or lithium within 6 weeks of randomization • planning to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary: To assess the efficacy of three doses of AFQ056 versus placebo in reducing the Aberrant Behavior Checklist – Community edition (ABC-C) Total score after 12 weeks of treatment in FXS patients with fully-methylated (FM) FMR1 gene. |
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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 | 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 |
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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.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | Information not present in EudraCT |
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 |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |