Clinical trial comparing the efficacy and safety of Rhudex granules with placebo in the treatment of the liver disease Primary Biliary Cholangitis

• Register: EUCTR
• Last refreshed on: 22 March 2021
• Main ID: EUCTR2020-001961-34-BE
• Date of registration: 23/10/2020
• Prospective Registration: Yes
• Primary sponsor: Dr. Falk Pharma GmbH
• Public title: Clinical trial comparing the efficacy and safety of Rhudex granules with placebo in the treatment of the liver disease Primary Biliary Cholangitis
• Scientific title: Double-blind, randomised, placebo-controlled, phase II dose-finding study comparing different doses of RhuDex granules with placebo in the treatment of primary biliary cholangitis - RhuDex vs placebo in PBC
• Date of first enrolment: 11/12/2020
• Target sample size: 136
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-001961-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Hungary, Netherlands, Slovakia, United Kingdom

Contacts

• Name: Headquarters
• Affiliation: Dr. Falk Pharma GmbH

• Name: Headquarters
• Affiliation: Dr. Falk Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
- Patient is able to understand the information on the trial and has signed the informed consent form,

- Male or female patients = 18 and < 75 years,

- PBC verified by at least 2 out of the following 3 criteria (consistent with EASL practice guidelines [2017]):
• Chronic cholestatic disease (e.g. elevated serum ALP) of at least 6 months duration,
• Positive AMA titer or presence of PBC-specific antibodies,
• Liver biopsy compatible with the diagnosis of non-cirrhotic PBC,

- UDCA treatment for at least 6 months (with a stable dose for = 3 months of at least 12 mg/kg/day) prior to baseline, and no foreseen changes of the dosing regimen throughout trial participation

- Inadequate response to UDCA treatment defined by serum ALP levels between 1.5x and 10x the upper limit of normal (ULN) at screening,

- Women of childbearing potential agree to use during the entire duration of the trial and until 4 weeks following the last dose of trial treatment a highly effective method of birth control.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 106
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
- History or presence of other relevant concomitant liver diseases

- Liver cirrhosis

- History or presence of hepatic decompensation (e.g. variceal bleeding hepatic encephalopathy or poorly controlled ascites),

- Serum albumin less than 3.2 g/dL, at screening,

- Any known relevant infectious disease (e.g. active tuberculosis, acquired immunodeficiency syndrome [AIDS]-defining diseases),

- Abnormal renal function (glomerular filtration rate estimated from cystatin C < 60 mL/min) at screening visit,

- Thyroid-stimulating hormone (TSH) > ULN at screening (elevated levels [4.2-10 µU/mL] are acceptable if free thyroxine 4 (fT4) is measured and within the normal range),

- Current history of significant alcohol consumption (> 30 g/day in men, > 20 g/day in women on average) for a period of more than 3 consecutive months within 1 year prior to screening,

- Any illness or medical conditions that are unstable or could jeopardise the safety of the patient and his/her compliance in the trial or might interfere with the trial results,

- Previous or concurrent cancer except cervical carcinoma in situ, treated basal cell carcinoma, or any cancer curatively treated < 3 years before trial entry,

- Existing or intended pregnancy or breast-feeding.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary biliary cholangitis
MedDRA version: 21.0 Level: PT Classification code 10080429 Term: Primary biliary cholangitis System Organ Class: 10019805 - Hepatobiliary disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: RhuDex 25 mg (31.75 mg RhuDex choline salt) granules
Pharmaceutical Form: Granules
INN or Proposed INN: RhuDex choline salt
Current Sponsor code: RhuDex choline salt
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 31.75-
Pharmaceutical form of the placebo: Gastro-resistant granules for oral suspension in sachet
Route of administration of the placebo: Oral use

Product Name: RhuDex 50 mg (63.5 mg RhuDex choline salt) granules
Pharmaceutical Form: Granules
INN or Proposed INN: RhuDex choline salt
Current Sponsor code: RhuDex choline salt
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 63.5-
Pharmaceutical form of the placebo: Gastro-resistant granules for oral suspension in sachet
Route of administration of the placebo: Oral use

Product Name: RhuDex 100 mg (127 mg RhuDex choline salt) granules
Pharmaceutical Form: Granules
INN or Proposed INN: RhuDex choline salt
Current Sponsor code: RhuDex choline salt
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 127-
Pharmaceutical form of the placebo: Gastro-resistant granules for oral suspension in sachet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of 3 doses of RhuDex vs placebo for the treatment of PBC in patients with an inadequate response to UDCA.

Timepoint(s) of evaluation of this end point: Throughout the study

Primary end point(s): Primary Efficacy Endpoint:

• Relative change (%) in Alkaline phosphatase (ALP) from baseline to End Of Trial (EoT).

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Safety Endpoints:

• Adverse Events,
• Vital signs (blood pressure, heart rate), body temperature, body weight and BMI,
• Haematology, serum chemistry, urinalysis, coagulation,
• ECG parameters (12 leads),
• Patient’s tolerability of the IMP.

Secondary Objective: - To identify efficacious RhuDex dose(s) for the treatment of PBC for further evaluation in phase III
- To study safety and tolerability of RhuDex

Secondary Outcome(s)

Secondary end point(s): Secondary Efficacy Endpoints:

- ALP at each trial visit (screening to follow-up),

- Absolute and relative changes (%) of ALP from baseline to each visit up to EOT, and from EOT to the follow-up visit,

- ?-GT, AST, ALT, and total and conjugated bilirubin levels at each trial visit (screening to follow-up),

- Absolute and relative changes (%) of ?-GT, AST, ALT and total and conjugated bilirubin levels from baseline to each visit up to EOT, and from EOT to the follow-up visit.

Timepoint(s) of evaluation of this end point: Throughout the study

Secondary ID(s)

RDG-1/PBC

2020-001961-34-DE

Source(s) of Monetary Support

Dr. Falk Pharma GmbH

Ethics review

Status: Approved
Approval date: 11/12/2020
Contact: