Phase II Double-Blind, Randomized, Placebo-Controlled Study of Glycerol Phenylbutyrate on Neurofilament Light Chain Levels in Corticobasal Syndrome Patients
- Trial ID
- 2024-516897-31-00
- Protocol
- PROFIL-2088-SIM-0032
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of glycerol phenylbutyrate compared to placebo in reducing the levels of neurofilament light chain (NfL) over a 26-week period in patients with corticobasal syndrome (CBS). This is clinically relevant as elevated NfL levels are associated with neurodegeneration, and their reduction could indicate a potential therapeutic effect in managing CBS. Additionally, the study aims to assess the safety and tolerability of glycerol phenylbutyrate in this patient population.
The secondary objective is to assess longitudinal changes in various clinical scales, including MDS-UPDRS Part III, PSPRS, PSP-CDS, CBFS, DATE, MoCA, SEADL, CGI-s, and PSP-QoL, between visits V1 and V3, comparing placebo- and verum-treated patients. These scales are critical for evaluating the progression and impact of CBS on patients' motor and cognitive functions, as well as their quality of life.
Participants
The clinical trial involves participants diagnosed with **Corticobasal Syndrome (CBS)**, including those with Progressive Supranuclear Palsy-CBS. The study population comprises both male and female subjects aged 18 years and older. Participants are required to have a stable medication regimen for at least one month prior to the trial and must not have regularly consumed glycerol phenylbutyrate in the six months preceding the study. The trial includes individuals capable of understanding the study information and providing informed consent, with women of childbearing potential adhering to strict birth control measures. The sponsor has not provided the total number of participants involved in the trial. The selection process ensures that participants are willing and able to comply with the trial procedures, and the study includes a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, placebo-controlled, parallel-group Phase II study designed to evaluate the efficacy, safety, and tolerability of **glycerol phenylbutyrate** in patients with **corticobasal syndrome** (CBS). The primary objective is to assess the reduction in neurofilament light chain (NfL) levels over a 26-week period. The trial will involve a comparison between the active treatment group receiving glycerol phenylbutyrate and a placebo group. The study is expected to conclude by September 30, 2025, with recruitment having commenced on July 1, 2023.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), diagnosis of CBS, and the ability to provide informed consent. The trial will include follow-up visits to monitor safety and efficacy endpoints, including the primary endpoint of longitudinal change in NfL levels and secondary endpoints involving clinical scales. The end-of-study visit will mark the completion of the participant's involvement, which is anticipated to last for the full 26-week treatment period unless early termination is warranted.
Early termination from the study may occur if participants experience adverse reactions that compromise safety, fail to comply with study procedures, or withdraw consent. Safety assessments will include monitoring adverse reactions, conducting laboratory evaluations, and performing physical and neurological examinations. The trial will ensure that all participants adhere to a stable medication regimen for at least one month prior to the first visit and throughout the study duration. Women of childbearing potential must adhere to strict contraceptive measures to participate.
Treatment
The clinical trial involves the administration of **RAVICTI 1.1 g/ml oral liquid**, which contains the active substance **glycerol phenylbutyrate**. This experimental medication is provided in an oral liquid pharmaceutical form and is intended for **oral use**. The maximum daily dose is 6 ml, with a total maximum dose of 1029 ml over the course of the study. The treatment period is set for 26 weeks. The medication is packaged and labeled specifically for the trial, ensuring compliance with regulatory standards. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.
In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, randomized, placebo-controlled study. The placebo is designed to match the experimental medication in appearance and administration route, ensuring that neither the participants nor the investigators can distinguish between the active treatment and the placebo. This approach is critical for maintaining the integrity of the study and for accurately assessing the efficacy and safety of glycerol phenylbutyrate in patients with corticobasal syndrome.
Efficacy
The efficacy of glycerol phenylbutyrate in patients with corticobasal syndrome (CBS) will be assessed through a double-blind, randomized, placebo-controlled phase II clinical trial. The primary efficacy endpoint is the longitudinal change in **neurofilament light chain (NfL)** levels in plasma, measured between the initial visit (V1) and the third visit (V3), comparing patients treated with glycerol phenylbutyrate to those receiving a placebo. This biomarker is a critical indicator of neuronal damage and is used to evaluate the treatment's impact on disease progression.
Secondary efficacy endpoints include the longitudinal changes in various clinical scales, such as MDS-UPDRS Part III, PSP-RS, PSP-CDS, CBFS, DATE, MoCA, SEADL, CGI-s, and PSP-QoL, between V1 and V3. These scales are utilized to assess motor and cognitive functions, quality of life, and overall clinical status, providing a comprehensive evaluation of the treatment's efficacy. The trial is designed to last 26 weeks, during which these parameters will be systematically collected and analyzed to determine the therapeutic benefits of glycerol phenylbutyrate compared to placebo.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 01 Jul 2023 | 32 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
RAVICTI 1.1 g/ml oral liquid | Test | ORAL LIQUID | ORAL USE | 6 | 26 | PRD7395693 |
hydroxypropyl methylcellulose HPMC 4000, sodium benzoate, propylene glycole, aqua destillata | Placebo | N/A | — | — | — | N/A |