Double-blind, randomized, placebo-controlled, phase II dose-finding study comparing different doses of Rhudex granules with placebo in the treatment of primary biliary cholangitis
- Conditions
- cholangitisinflamnation in bile duct10017628
- Registration Number
- NL-OMON55327
- Lead Sponsor
- AML Clinical Services BV
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
Patients who meet all of the following criteria can be enrolled into the trial:
1. Patient is able to understand the information on the trial and has signed
the informed consent form,
2. Male or female patients >= 18 and < 75 years,
3. 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,
4. 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,
5. Inadequate response to UDCA treatment defined by serum ALP levels between
1.5x and 10x the upper limit of normal (ULN) at screening,
6. 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, defined as those which result in a low
failure rate (i.e. less than 1% per year) when used consistently and correctly
such as implants, injectables, combined oral contraceptive methods, some
intrauterine devices (IUDs), sexual abstinence, or vasectomised partner. Women
of non-childbearing potential (surgically sterile [e.g. hysterectomy, bilateral
salpingectomy, bilateral oophorectomy], or postmenopausal with at least 2 years
without spontaneous menses) may be included. The investigator is responsible
for determining whether the patient uses adequate birth control for trial
participation
Patients who meet one or more of the following criteria are not allowed to be
enrolled into the trial:
1. History or presence of other relevant concomitant liver diseases including:
• Positive hepatitis B or C serology: hepatitis B surface antigen (HBsAg+),
antibodies against hepatitis B core antigen (anti-HBc+), antibodies against
hepatitis C virus (anti-HCV+),
Note: Patients with anti-HBc+ only and negative hepatitis B virus
(HBV)-deoxyribonucleic acid (DNA) as well as patients with anti-HCV+ only and
negative HCV-ribonucleic acid (RNA) may be included
Primary Sclerosing Cholangitis,
• Wilson*s Disease,
• Haemochromatosis,
• Current histologic and serologic evidence to support a clinical diagnosis of
concomitant autoimmune hepatitis requiring treatment,
• Nonalcoholic steatohepatitis (NASH),
• Alcoholic steatohepatitis (ASH),
• Cholangiocarcinoma,
• Drug-induced liver disease,
• Suspected or proven liver cancer.
2. Treatment with any of the following drugs within the last 4 weeks prior
to screening: any glucocorticosteroids, azathioprine or other immunosuppressive
drugs (e.g. cyclophosphamide, cyclosporine, methotrexate, tacrolimus,
6-mercaptopurine, colchicine) orpentoxyfylline,
Note: Treatment with dermal, inhalative, or nasal topical glucocorticosteroids
for up to 10 days within the last 4 weeks prior to screening or as planned
concomitant treatment for up to 10 days/4 weeks is allowed.
3. Treatment with farnesoid X receptor-agonists and biologics (e.g. anti-TNF-a
therapy) within the last 8 weeks prior to screening,
4. Treatment with fibrates unless on stable dose for 8 weeks prior to screening
and no foreseen changes of the dosing regimen throughout trial participation,
5. Liver cirrhosis confirmed by an accepted diagnostic procedure (e.g.
histology, fibrosis-4 [FIB-4] score > 4.03, fibroscan >= 16.9 kPa ),
6. History or presence of hepatic decompensation (e.g. variceal bleeding
hepatic encephalopathy or poorly controlled ascites),
7. Serum albumin less than 3.2 g/dL, at screening,
8. Total bilirubin > 2x ULN, at screening,
9. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5x ULN
at screening visit,
10. History of stroke or coronary artery disease,
11. History of sudden death or cardiovascular death before the age of 50 in any
first degree relative,
12. History or family history of hereditary clotting disorder,
13. Any known relevant infectious disease (e.g. active tuberculosis, acquired
immunodeficiency syndrome-defining diseases),
14. Abnormal renal function (glomerular filtration rate estimated from cystatin
C < 60 mL/min) at screening visit,
15. Thyroid-stimulating hormone > ULN at screening (elevated levels [4.2-10 µU/
mL] are acceptable if free thyroxine 4 is measured and within the normal range),
16. 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,
17. Inability to reliably quantify alcohol consumption as judged by the
investigator,
18. 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,
19. Previous and concurrent HIV infection,
20. Previous or concurr
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Relative change (%) in ALP from baseline to EOT.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Proportion of patients with at least 10%, 20%, and 40% reduction in ALP<br /><br>between baseline and EOT,<br /><br>• Proportion of patients with normalisation of ALP (< ULN) at least at one<br /><br>post-baseline visit up to EOT,<br /><br>• Proportion of patients with partial normalisation of ALP (< 1.5x ULN) at<br /><br>least at one post-baseline visit up to EOT,<br /><br>• ALP at each trial visit (screening to follow-up),<br /><br>• Absolute and relative changes (%) of ALP from baseline to each visit up to<br /><br>EOT, and from EOT to the follow-up visit,<br /><br>• Gamma-glutamyltransferase (γ-GT), AST, ALT, and total and conjugated<br /><br>bilirubin levels at each trial visit (screening to follow-up),<br /><br>• Absolute and relative changes (%) of γ-GT, AST, ALT and total and conjugated<br /><br>bilirubin levels from baseline to each visit up to EOT, and from EOT to the<br /><br>follow-up visit.</p><br>