Double-blind, randomised, prospective, placebo controlled parallel group phase II study to investigate the effect of glycerol phenylbutyrate (GPB) on neurofilament light chain (NfL) levels in patients with corticobasal syndrome (CBS)

Start 1 Dec 2023 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 2 sites · Protocol PROFIL-2088-SIM-0032

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Ongoing, recruitment ended

Participants planned 32

Countries 1

Sites 2

Corticobasal Syndrome (CBS)

To assess the efficacy of glycerol phenylbutyrate vs. placebo in reducing the levels of neurofilament light chain (NfL) during 26 weeks of exposure to glycerol phenylbutyrate as well as safety and tolerability of glycerol phenylbutyrate in patients with CBS.

Key facts

Sponsor: Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Trial duration: 1 Dec 2023 → ongoing
Decision date (initial): 2024-09-26
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes

External identifiers

EU CT number: 2024-516897-31-00
EudraCT number: 2022-002988-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy

Secondary objectives 1

To assess longitudinal changes in clinical scales (MDS-UPDRS Part III, PSPRS, PSP-CDS, CBFS, DATE, MoCA, SEADL, CGI-s, PSP-QoL) between V1 and V3 comparing placebo- vs. verum-treated patients

Conditions and MedDRA coding

Corticobasal Syndrome (CBS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

Age: ≥ 18 years
„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)
No regular consumption of glycerol phenylbutyrate within the last 6 months prior to V1
Capable of thoroughly understanding all information given and giving full informed consent according to GCP
Capability and willingness to comply with the procedures of the clinical trial
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
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 9

Neurodegenerative diseases other than CBS
Underlying Alzheimer’s pathology as defined by positive β-amyloid- PET or reduced Aβ 1-42 in CSF
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
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
Treatment with valproic acid, haloperidol or probenecid
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
Persistent abuse of medication, drugs or alcohol
Current or planned pregnancy or breast-feeding in females
Other severe medical conditions upon the discretion of the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

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.
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
Tolerability: Number of subjects (and % of the intention-to-treat population), who discontinue the clinical trial due to adverse reactions

Secondary endpoints 1

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

RAVICTI 1.1 g/ml oral liquid

PRD7395693 · Product

Active substance: Glycerol Phenylbutyrate
Pharmaceutical form: ORAL LIQUID
Route of administration: ORAL USE
Max daily dose: 6 ml millilitre(s)
Max total dose: 1029 ml millilitre(s)
Max treatment duration: 26 Week(s)
Authorisation status: Authorised
ATC code: A16AX09 — -
Marketing authorisation: EU/1/15/1062/001
MA holder: IMMEDICA PHARMA AB
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Packaged and labeled

Placebo 1

hydroxypropyl methylcellulose HPMC 4000, sodium benzoate, propylene glycole, aqua destillata

N/A · Product

Other product name: N/A
Pharmaceutical form: N/A
ATC code: N/A — N/A
Marketing authorisation: N/A
MA holder: N/A
MA country: Iceland
Paediatric formulation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

Sponsor organisation: Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
Address: Ismaninger Strasse 22, Au-Haidhausen Au-Haidhausen
City: Munich
Postcode: 81675
Country: Germany

Scientific contact point

Organisation: Klinikum rechts der Isar der TU Muenchen AöR
Contact name: Prof. Dr. Johannes Levin

Public contact point

Organisation: Klinikum rechts der Isar der TU Muenchen AöR
Contact name: Prof. Dr. Mikael Simons

Locations

1 EU/EEA country · 2 investigational sites

By country

Country	MS status	Planned subjects	Sites
Germany	Ongoing, recruitment ended	32	2
Rest of world	—	0	—

Investigational sites

Germany

2 sites · Ongoing, recruitment ended

Klinikum rechts der Isar der TU Muenchen AöR

Klinik und Poliklinik für Neurologie, Feodor-Lynen-Strasse 17, Hadern, Munich

Klinikum der Universitaet Muenchen AöR