E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Corticobasal Syndrome (CBS) |
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E.1.1.1 | Medical condition in easily understood language |
Corticobasal Syndrome (CBS) |
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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 | PT |
E.1.2 | Classification code | 10078208 |
E.1.2 | Term | Corticobasal degeneration |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 assess the efficacy of glycerol phenylbutyrate vs. placebo in reducing the levels of neurofilament light chain (NfL) during 26 weeks of exposure to glyc-erol phenylbutyrate as well as safety and tolerability of glycerol phenylbutyrate in patients with CBS. |
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E.2.2 | Secondary objectives of the trial |
To assess longitudinal changes in clinical scales (MDS-UPDRS Part III, PSP-RS, PSP-CDS, CBFS, DATE, MoCA, SEADL, CGI-s, PSP-QoL) between V1 and V3 comparing placebo- vs. verum-treated patients |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age: ≥ 18 years 2. „clinical possible“ or „clinical probable“ CBS (Armstrong et al., Neurol-ogy, 2013 80;496-503) and patients with Progressive Supranuclear Palsy-CBS according to Höglinger et al. (Mov Disord. 2017 Jun;32(6):853-864) 3. No regular consumption of glycerol phenylbutyrate within the last 6 months prior to V1 4. Capable of thoroughly understanding all information given and giving full informed consent according to GCP 5. Capability and willingness to comply with the procedures of the clini-cal trial 6. Women of childbearing age must be non-lactating and surgically ster-ile or using a highly effective method of birth control and have a nega-tive pregnancy test. In case of using a hormonal contraception, the method must be sup-plemented with a barrier method (preferably male condom). Acceptable methods of birth control with a low failure rate i.e. less than 1% per year when used consistently and cor-rect are such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence (defined as refraining from heterosexual intercourse during the clinical trial) or vasecto-mized partner. Unacceptable birth control methods are: periodic abstinence (calen-dar, symptothermal, post-ovulation methods), withdrawal (coitus inter-ruptus), spermicides only and lactational amenorrhoea method (LAM). Female condom and male condom should not be used together. 7. A stable regimen for at least 1 month prior to V1 and no foreseeable need to change the regimen throughout the 26 week treatment period for a. drugs acting against Parkinsonism (e.g. Levodopa, Dopa-mine-Agonists, Amantadine and MAO-B-Inhibitors) b. other CNS-active substances including e.g. antidepressants and antidementia drugs
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E.4 | Principal exclusion criteria |
1. Neurodegenerative diseases other than CBS 2. Underlying Alzheimer’s pathology as defined by positive β-amyloid-PET or reduced Aβ 1-42 in CSF 3. Participation in another clinical trial involving administration of an in-vestigational medicinal product within 1 month or 5 half-lives of the investigational medicinal product, whichever is longer, prior to V1 4. Known hypersensitivity to glycerol phenylbutyrate or its further components, or to drugs with a similar chemical structure or to any of the components of the placebo 5. Treatment with valproic acid, haloperidol or probenecid 6. A physical or psychiatric condition (e.g. frontal lobe syndrome, psychotic disorder or major depression), which at the investigator’s discre-tion may put the subject at risk, may confound the trial results or may interfere with the subject’s participation in this clinical trial 7. Persistent abuse of medication, drugs or alcohol 8. Current or planned pregnancy or breast-feeding in females 9. Other severe medical conditions upon the discretion of the investiga-tor
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: The primary outcome measure will be the longitudinal change of NfL in plasma between V1 and V3 comparing GPB vs. Placebo-treated pa-tients. Primary Endpoints for Safety and Tolerability: Safety • Incidence of specific AEs • Safety laboratory values (basic clinical chemistry) • Vital signs (blood pressure, heart rate, temperature) • Physical and neurological examination • Survival time and survival rate during the study period Tolerability • Number of subjects (and % of the intention-to-treat population), who discontinue the clinical trial due to adverse reactions
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Longitudinal changes in clinical scales (MDS-UPDRS Part III, PSP-RS, PSP-CDS, CBFS, DATE, MoCA, SEADL, CGI-s, PSP-QoL) between V1 and V3 comparing placebo- vs. verum-treated patients |
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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 | No |
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 | Yes |
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 | 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 | 2 |
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 | 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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final analyses of primary endpoint |
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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 | |