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 |
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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 | LLT |
E.1.2 | Classification code | 10034008 |
E.1.2 | Term | Parkinson's syndrome |
E.1.2 | System Organ Class | 100000004852 |
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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 compare the effects of intermittent bilateral intraputamenal GDNF infusions on OFF-state motor function after 18 months of treatment with the effects after 9 months of treatment in subjects who completed in Study 2553. |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of intermittent bilateral intraputamenal GDNF infusions on ON-state motor function, motor complications, & ON- & OFF-state activities of daily living after 18m treatment with the effects after 9m treatment in subjects who completed Study 2553.
• To assess the safety of intermittent bilateral intraputamenal GDNF infusions at 18m in subjects who received GDNF or placebo for 9m in Study 2553.
• To explore the effects of intermittent bilateral intraputamenal GDNF infusions on other motor & non-motor functions, quality of life assessments, & imaging endpoints at 18 months in subjects who completed Study 2553.
• To compare the results for various motor outcomes between the subjects who started GDNF early (i.e. were randomized to GDNF in Study 2553) & those who started GDNF late (i.e. were randomized to placebo in Study 2553).
• Pilot Extension: To generate long-term safety data & provide continued access to GDNF until results of Study 2553 are available |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to qualify for entry into the study, subjects MUST meet all of the following criteria:
1. Enrolled and completed treatment in the Pilot or Primary Study Stages of Study 2553.
2. Females of childbearing potential must have a negative pregnancy test at study entry and be willing to use an approved (by the PI or designee) form of contraception until the end of the study.
3. Males with female partners of childbearing potential must be willing to use condoms for contraception until the end of the study.
4. Provision of informed consent. |
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria will NOT be eligible for inclusion in the study:
1. Discontinued treatment early in Study 2553.
2. Had any significant (in the opinion of the PI or designee) protocol deviation in Study 2553; this includes receipt of any disallowed anti-parkinsonian treatment or any investigational treatment.
3. Presence of clinically significant (in the opinion of the PI) depression.
4. MoCA score < 24 at the final assessment in Study 2553.
5. Any new medical condition which might impair outcome measure assessments or safety measures including ability to undergo MRI scanning. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the percentage change from baseline to the end of treatment in the practically defined OFF-state UPDRS motor score (part III). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
9 months of treatment in extension study (18 months treatment overall including treatment in study 2553)
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E.5.2 | Secondary end point(s) |
• Percentage change from baseline to the end of treatment in UPDRS motor score (part III) in the ON-state (following a levodopa challenge)
• Percentage change from baseline to the end of treatment in UPDRS ADL (part II) .
• Change from baseline to the end of treatment in PD diary ratings; i.e., total OFFtime per day, total good quality ON-time (ON without dyskinesias or ON with non-troublesome dyskinesias) and ON-time with troublesome dyskinesias |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
9 months of treatment in extension study (18 months treatment overall including treatment in study 2553)
Pilot subjects only will be eligible for up to an additional 80 weeks of Treatment (Pilot Extension). |
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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) | 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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
All patients previously completed study 2553 |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |