Display again
NCT03633227 | SNCTP000003721

Eine placebokontrollierte Studie zur Beurteilung der Verteilung und Abbau, sowie Sicherheit von Obeticholsäure bei Patienten mit primär biliäre Zirrhose und mäßiger bis schwerer Leberfunktionsstörung

Data source: BASEC (Imported from 24.05.2020), WHO (Imported from 22.03.2020)
Changed: 07.04.2020
Disease category: Anderes

Brief description of trial (Source of data: BASEC)

In dieser Studie wird die primär biliäre Cholangitis (auch bekannt als primär biliäre Zirrhose oder PBC) untersucht. Wir führen diese Studie durch, um zusätzliche Informationen über Obeticholsäure und ihre Wirkung auf Ihre PBC-Erkrankung zu gewinnen, wenn diese gemeinsam mit Ursodeoxycholsäure verabreicht wird und der Sponsor möchte den klinischen Nutzen für Patienten bestätigen. Darüber hinaus bewertet der Sponsor die Sicherheit des Arzneimittels sowie die Verteilung und den Abbau des Studienmedikaments. Dies wird Pharmakokinetik genannt.

Health conditions investigated (Source of data: BASEC)

primär biliäre Zirrhose und mäßige bis schwerer Leberfunktionsstörung

Health conditions (Source of data: WHO)

Liver Cirrhosis, Biliary

Rare disease (Source of data: BASEC)

Yes

Intervention investigated (e.g. drug, therapy or campaign) (Source of data: BASEC)

Der Zweck dieser Studie besteht darin, herauszufinden, wie das Prüfpräparat, im Körper absorbiert und verteilt wird und wie das Prüfpräparat aus dem Körper ausgeschieden wird. Dies wird als Pharmakokinetik bezeichnet. Zudem wird auch die Sicherheit des Prüfpräparats untersuchen.

Interventions (Source of data: WHO)

Drug: Obeticholic Acid (OCA);Drug: Placebo

Criteria for participation in trial (Source of data: BASEC)

1. Eine definitive oder wahrscheinliche Diagnose von primärer biliäre Cholangitis
2. Hinweise auf eine Zirrhose
3. Leberfunktionsstörungen während der Voruntersuchung

Exclusion criteria (Source of data: BASEC)

1. Nicht-zirrhotische oder zirrhotische biliäre Cholangitis
2. Lebertransplantation oder Organtransplantation in der Krankengeschichte
3. Alkohol- oder Drogenmissbrauch innerhalb von 12 Monaten vor der Voruntersuchung

Inclusion/Exclusion Criteria (Source of data: WHO)


Inclusion Criteria:

1. A definite or probable diagnosis of PBC (consistent with American Association for the
Study of Liver Diseases [AASLD] and European Association for the Study of the Liver
[EASL] Practice Guidelines [Lindor 2009, EASL 2009]), defined as having =2 of the
following 3 diagnostic factors:

- History of elevated ALP levels for at least 6 months

- Positive antimitochondrial antibody (AMA) titer or if AMA negative or low titer
(=1:80), PBC specific antibodies (anti-GP210 and/or anti-SP100) and/or antibodies
against the major M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase
complex)

- Liver biopsy consistent with PBC (collected at any time prior to Screening)

2. Evidence of cirrhosis including at least one of the following:

- Biopsy results consistent with PBC Stage 4

- Liver stiffness as assessed by Transient Elastography (TE) Median Value =16.9kPa

- Clinical evidence in the absence of acute liver failure consistent with cirrhosis
including: gastroesophageal varices, ascites, radiological evidence of cirrhosis
(nodular liver or enlargement of portal vein and splenomegaly)

- Combined low platelet count (<140 000/mm3) with

- persistent decrease in serum albumin, or

- elevation in prothrombin time /INR (not due to antithrombotic agent use), or

- elevated bilirubin (2× ULN)

3. Satisfy the criteria of the modified CP classification for hepatic impairment during
Screening:

- Moderate: CP-B (Scores 7 to 9) or

- Severe: CP-C (Scores 10 to 12)

4. MELD score of 6 to 24 at Screening

5. Taking UDCA for at least 12 months (stable dose for =3 months) prior to Day 1, or
unable to tolerate or unresponsive to UDCA (no UDCA for =3 months)

Exclusion Criteria:

1. Non-cirrhotic or cirrhotic CP-A (Mild; Score 5 to 6)

2. History of liver transplant or organ transplant

3. History of alcohol or drug abuse within 12 months prior to Screening

4. Hepatic encephalopathy (as defined by a West Haven score of =2 [AASLD, EASL 2014])

5. History or presence of other concomitant liver diseases including:

- Hepatitis C virus infection and RNA positive

- Active hepatitis B infection; however, patients who have seroconverted (hepatitis
B surface antigen and hepatitis B e antigen negative) may be included in this
study after consultation with the medical monitor

- Primary sclerosing cholangitis

- Alcoholic liver disease

- Definite autoimmune liver disease or overlap hepatitis

- Gilbert's Syndrome

6. In the opinion of the Investigator, fluctuating or rapidly deteriorating hepatic
function prior to randomization

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03633227

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03633227

Further information on trial

Date trial registered

08.04.2018

Incorporation of the first participant

22.06.2018

Recruitment status

Recruiting

Academic title (Source of data: WHO)

A Phase 4, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Pharmacokinetics and Safety of Obeticholic Acid in Patients With Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment

Type of trial (Source of data: WHO)

Interventional

Design of the trial (Source of data: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).

Phase (Source of data: WHO)

Phase 4

Primary end point (Source of data: WHO)

Evaluate maximum concentration (Cmax) of OCA, its conjugates and total OCA (sum of OCA and its conjugates);Evaluate area under the concentration curve versus time curve from 0 to 24 hours (AUC 0-24) of OCA, its conjugates and total OCA;Evaluate safety and tolerability as assessed by the incidence of treatment emergent adverse events and serious treatment emergent adverse events comparing OCA to placebo

Secundary end point (Source of data: WHO)

Evaluate the effect of OCA treatment compared to placebo on the model of end-stage liver disease (MELD) and its components;Evaluate the effect of OCA treatment compared to placebo on Child-Pugh score and its components;Evaluate the effect of OCA treatment compared to placebo on total bilirubin (mg/dL) and direct bilirubin (mg/dL);Evaluate the effect of OCA treatment compared to placebo on alkaline phosphatase (U/L), alanine aminotransferase (U/L), aspartate transaminase (U/L), and gamma glutamyl transaminase (U/L);Evaluate the effect of OCA treatment compared to placebo on platelets (109/L);Evaluate the effect of OCA treatment compared to placebo on fibroblast growth factor-19 (pg/mL);. Evaluate the effect of OCA treatment compared to placebo on 7a hydroxy-4-cholesten-3-one (ng/mL);Evaluate the effect of OCA treatment compared to placebo on plasma bile acids (µmol/L)

Contact information (Source of data: WHO)

Please refer to primary and secondary sponsors

Trial sites

Trial sites in Switzerland (Source of data: BASEC)

Bern

Countries (Source of data: WHO)

Argentina, Australia, Belgium, Brazil, Estonia, Germany, Hungary, Italy, Lithuania, Spain, United States

Contact for further information on the trial

Details of contact in Switzerland (Source of data: BASEC)

Beat Weiss
+41-31-543 01 19
b.weiss@weiss-company.ch

Contact for general information (Source of data: WHO)

Christian Weyer, M.D.;Judith Romano
Intercept Pharmaceuticals
+1(646) 757-2335
judith.romano@interceptpharma.com

Contact for scientific information (Source of data: WHO)

Christian Weyer, M.D.;Judith Romano
Intercept Pharmaceuticals
+1(646) 757-2335
judith.romano@interceptpharma.com

Principal Sponsor/Investigator

Principal sponsor (Source of data: WHO)

Intercept Pharmaceuticals

Further trial identification numbers

BASEC ID (Source of data: BASEC)

2019-00181

Secondary ID (Source of data: WHO)

747-401