E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pantothenate Kinase-Associated Neurodegeneration (PKAN) |
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E.1.1.1 | Medical condition in easily understood language |
Neurodegeneration with brain iron accumulation |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053643 |
E.1.2 | Term | Neurodegenerative disorder |
E.1.2 | System Organ Class | 10029205 - Nervous system 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 long-term safety and tolerability of the drug deferiprone in patients with pantothenate kinase-associated neurodegeneration (PKAN). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the change in severity of dystonia (a state of abnormal muscle tone resulting in muscular spasm and abnormal posture, typically due to neurological disease) over time in patients with PKAN treated with deferiprone. To evaluate global improvement over time in patients with PKAN treated with deferiprone |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completed study TIRCON2012V1 2. Sexually active females of childbearing potential, including those who are perimenopausal (defined as less than 2 years since last menstrual period) must have a negative pregnancy test result at Visit 1 (if applicable; in cases where the investigator determines there is no reasonable risk of pregnancy because of significant incapacity, pregnancy testing will not be performed). In addition, if applicable, they must meet at least one of the following criteria: Use an effective method of contraception during the study and within 30 days following their last dose of study medication, OR Participate in a non-heterosexual lifestyle, OR Have a male sexual partner who has been sterilized (supporting evidence required) Approved methods of contraception will consist of the following or must follow local requirements: Oral contraceptive used in conjunction with condom, diaphragm, or spermicide Hormonal implant used in conjunction with condom, diaphragm, or spermicide Injectable contraceptive used in conjunction with condom, diaphragm, or spermicide Diaphragm or condom used with spermicide Abstinence, which must be true abstinence that is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods of contraception. If a hormonal contraception is used, it should have a Pearl index <1%. Female patients who meet any of the following criteria are not of childbearing potential and therefore do not need to practice contraception: Post-menopausal (last menstrual period > 2 years ago) Had a tubal ligation (supporting evidence required) Had a hysterectomy or oophorectomy (supporting evidence required)
3. Fertile heterosexual males and/or their partners must agree to use an effective method of contraception (as defined in criterion # 2) during the study and for 30 days following the last dose of study medication
4. Patients and/or their authorized legal representatives must provide signed and dated written informed consent prior to the first study intervention, and patients must be able to adhere to study restrictions, appointments, and evaluation schedules. Patients who are minors must sign an assent form as per local regulatory requirements. |
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E.4 | Principal exclusion criteria |
1. Withdrew from the study TIRCON2012V1 for reasons of safety
2. Plan to participate in another clinical trial at any time from the day of enrolment until 30 days post-treatment in the current study
3. Presence of any medical, psychological, or psychiatric condition which in the opinion of the investigator would cause participation in the study to be unwise.
4. Pregnant, breastfeeding, or planning to become pregnant during the study period. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events (AEs): Frequency, severity, time to onset, duration, and relatedness to study product - Serious adverse events (SAEs): Frequency, severity, time to onset, duration, and relatedness to study product - Number of discontinuations due to AEs - Hematology assessments - Blood chemistry assessments - ECG assessments |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints:
Baseline, 12m, 18m |
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E.5.2 | Secondary end point(s) |
All patients: Change in the BAD total score from baseline (defined as prior to the start of deferiprone therapy) to Visit 4, as assessed by central evaluation of videotapes
Proportion of patients with improved or unchanged BAD scale total score between baseline and Visit 4 (responder analysis)
Change from baseline to Visit 4 in BAD scale score per body region (eyes, mouth, neck, trunk, and each upper and lower extremity), as assessed by central evaluation of videotapes
Change in score on the PGI-I from baseline to Visit 4
Proportion of patients showing an improvement on PGI-I at Visit 4 (responder analysis) The time points for these efficacy endpoints are defined as follows: For patients who received deferiprone in the earlier study, the baseline visit of that study will be treated as the baseline visit of TIRCON2012V1-EXT as well. Thus, Visit 1 of the extension study (Week 0) will be Year 1.5, and Visit 4 (Week 78) will be Year 3. For patients who received placebo in the earlier study, Visit 1 of the extension study (Week 0) will be the baseline visit. Thus, Visit 4 (Week 78) will be Year 1.5.
Patients who received placebo in initial study: For this group only, for each measure, the changes seen between the start and completion of study TIRCON2012V1 (i.e., following 18 months on placebo) will be compared against the changes seen between the start and completion of study TIRCON2012V1-EXT (i.e.,following 18 months on deferiprone), as follows:
Comparison of change in BAD total score from baseline to completion of the initial study vs. change in BAD total score from baseline to completion of the extension study Comparison of the proportion of patients with improved or unchanged BAD scale total score between baseline and completion of the initial study vs. the proportion with improved or unchanged BAD scale total score from baseline to completion of the extension study (responder analysis)
Comparison of the change in BAD score per body region between baseline and completion of the initial study vs. change in BAD score per body region between baseline and completion of the extension study
Comparison of change in PGI-I score from baseline to completion of the initial study vs. change in PGI-I score from baseline to completion of the extension study
Comparison of the proportion of patients showing an improvement on PGI-I at completion of the initial study vs. the proportion showing an improvement at completion of the extension study (responder analysis) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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.8.3 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | Yes |
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 |
Germany |
Italy |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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4 weeks following LVLS to allow for any AE's to be reported. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 31 |