GLYCEROL PHENYLBUTYRATE for Corticobasal syndrome

Inclusion criteria

• {"criterion_text":"- Age: ≥ 18 years\n- „clinical possible“ or „clinical probable“ CBS (Armstrong et al., Neurology, 2013 80;496-503) and patients with Progressive Supranuclear Palsy-CBS according to Höglinger et al. (Mov Disord. 2017 Jun;32(6):853-864)\n- No regular consumption of glycerol phenylbutyrate within the last 6 months prior to V1\n- Capable of thoroughly understanding all information given and giving full informed consent according to GCP\n- Capability and willingness to comply with the procedures of the clinical trial\n- Women of childbearing age must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. In case of using a hormonal contraception, the method must be supplemented 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 correct 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 vasectomized partner. Unacceptable birth control methods are: periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only and lactational amenorrhoea method (LAM). Female condom and male condom should not be used together\n- 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, Dopamine- Agonists, Amantadine and MAO-B-Inhibitors) b.) other CNS-active substances including e.g. antidepressants and antidementia drugs"}

Exclusion criteria

• {"criterion_text":"- Neurodegenerative diseases other than CBS\n- Underlying Alzheimer’s pathology as defined by positive β-amyloid- PET or reduced Aβ 1-42 in CSF\n- Participation in another clinical trial involving administration of an investigational medicinal product within 1 month or 5 half-lives of the investigational medicinal product, whichever is longer, prior to V1\n- 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\n- Treatment with valproic acid, haloperidol or probenecid\n- A physical or psychiatric condition (e.g. frontal lobe syndrome, psychotic disorder or major depression), which at the investigator’s discretion may put the subject at risk, may confound the trial results or may interfere with the subject’s participation in this clinical trial\n- Persistent abuse of medication, drugs or alcohol\n- Current or planned pregnancy or breast-feeding in females\n- Other severe medical conditions upon the discretion of the investigator"}

Primary endpoints

• {"endpoint_text":"- 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 patients.","definition_or_measurement_approach":"Longitudinal change of neurofilament light chain (NfL) measured in plasma between visit V1 and V3 comparing glycerol phenylbutyrate (GPB) versus placebo-treated patients."}
• {"endpoint_text":"- Safety: Incidence of ARs, Safety laboratory evaluation (basic clinical chemistry), Vital signs (blood pressure, heart rate, temperature), Physical and neurological examination, Survival time and survival rate during the study period","definition_or_measurement_approach":"Safety assessed by incidence of adverse reactions (ARs), basic clinical chemistry laboratory evaluations, recording of vital signs, physical and neurological examinations, and assessment of survival time and survival rate during the study period."}
• {"endpoint_text":"- Tolerability: Number of subjects (and % of the intention-to-treat population), who discontinue the clinical trial due to adverse reactions","definition_or_measurement_approach":"Tolerability measured as the count and percentage of subjects in the intention-to-treat population who discontinue the trial due to adverse reactions."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change in the listed clinical rating scales between visit V1 and V3 comparing placebo-treated versus verum (GPB)-treated patients."}

Germany

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

15-09-2025

Processing Time Days

360

Number Of Sites

2

Number Of Participants

32

Primary sponsor

Full Name

Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany