E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Charcot-Marie-Tooth Disease type 1A |
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E.1.1.1 | Medical condition in easily understood language |
Charcot-Marie-Tooth Disease type 1A |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008414 |
E.1.2 | Term | Charcot-Marie-Tooth disease |
E.1.2 | System Organ Class | 100000004850 |
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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 |
The main objective of the study is to assess the long-term safety and tolerability of PXT3003 up to 2 years, and to increase the exposed population receiving PXT3003 for at least 9 months. |
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E.2.2 | Secondary objectives of the trial |
To gather up-to-2-year data to estimate the long term effect of PXT3003 on clinical, functional and electrophysiological endpoints;
- To compare the effect of PXT3003 in patients receiving PXT3003 active dose from the start of the primary study to patients assigned to a delayed start (i.e., who received placebo during the primary study) in order to show if PXT3003 slows the progression of the disease
- To assess the evolution of potential blood biomarkers and molecular changes in skin biopsy on longer term.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
• Skin Biopsy (ancillary sub-study) for molecular biology will be done at the end of the study (9-month visit)
• MRI measure (ancillary sub-study) of muscle/fat index in the leg (by MRI quantification of lower limb muscles and fatty muscle infiltration) will be performed at the end of the study (9-month visit).
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E.3 | Principal inclusion criteria |
Male or female patients with all of the following inclusion criteria will be considered for randomization:
1. Patient previously randomized to the initial PLEO-CMT study (protocol CLN-PXT3003-02) and having completed 15 months of double-blind treatment in that study, including all procedures required at the Study Termination visit (V6) or patient under prematurely discontinued from CLN-PXT-3003-02 (due to sponsor decision on September 18th, 2017) must have performed an early V6.
2. Patients who completed V6 assessments within the 4 weeks prior extension study or patients who have completed a new baseline visit (VB) if the V6 assessments were not completed in the 4 weeks prior study entry.
3. Patient providing a signed written informed consent to participate in the extension study and willing and able to comply with all study procedures and scheduled visits. All minor patients who were included in the primary study will have reached their majority, so only adult patients will be included in the extension study.
4. Female patients must agree to continue using an approved method of birth control throughout the extension study |
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E.4 | Principal exclusion criteria |
Patients with any of the following criteria will be excluded from entry:
1. Presenting any clinically significant change in health status that, in the opinion of the Investigator, would prevent the subject from participating in this study or successfully completing this study.
2. Any unauthorized concomitant treatments, in the 4 weeks preceding study entry, as study CLN-PXT3003-02. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the safety and tolerability of PXT3003 in CMT1A patients during a long term period, the primary endpoint will be the incidence of Treatment-Emergent Adverse Events (TEAEs) Related to the Investigational Product during the follow-up, in patients exposed to PXT3003 for up to 24 months or 9 months.
The incidence of TEAEs in the two groups P / D1-9m and P/ D2-9m will be compared to the first 9-month placebo period in the primary study.
The incidence of TEAEs in the two groups D1-24m, D2-24m will be compared to the first 9-month period in the primary study for their corresponding group.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The incidence of TEAEs in the two groups P/ D1-9m and P / D2-9m will be compared to the first 9-month placebo period in the primary study.
The incidence of TEAEs in the two groups D1-24m, D2-24m will be compared to the first 9-month period in the primary study for their corresponding group
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E.5.2 | Secondary end point(s) |
Secondary safety endpoints will be:
- The incidence of all Treatment-Emergent Adverse Events (TEAEs) and evaluation of their type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome;
- The incidence of AEs leading to withdrawal of study drug;
- The changes in laboratory parameters, ECGs, vital signs and physical examinations;
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For the patients receiving up to 24 months of active dose along the two successive studies (from groups D1-24m and D2-24m) the clinical response will be assessed by the change from V1/baseline of each endpoint.
For the patients who received placebo during the 15-month primary study and active drug during the 9-month extension study (from groups P/D1-9m and P/D2-9m) the clinical response will be assessed after 9 months of PXT3003 treatment by the change from V6/baseline.
The Percentage of responders to PXT3003 defined as a patients improving on ONLS at end of treatment (V9) will be assessed in the patients receiving the active dose of PXT3003 during up to 24 months (from groups D1-24m, D2-24m).
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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 | 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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
Belgium |
Canada |
France |
Germany |
Netherlands |
Spain |
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 | 8 |
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 | 8 |