Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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1 February 2022 |
Main ID: |
EUCTR2014-005012-42-AT |
Date of registration:
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28/09/2015 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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A Phase 4 clinical trial to measure the effect of Obeticholic acid against a placebo, in conjunction with standard treatment, on selected clinical measurements in patients with the liver disease, Primary Biliary Cholangitis.
The COBALT Study Clinical Outcomes with OBeticholic Acid in Liver Treatment (COBALT)
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Scientific title:
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A Phase 4, Double Blind, Randomized, Placebo Controlled, Multicenter Study Evaluating the Effect of Obeticholic Acid on Clinical Outcomes in Subjects with Primary Biliary Cholangitis.
The COBALT Study Clinical Outcomes with OBeticholic Acid in Liver Treatment (COBALT)
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Date of first enrolment:
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26/11/2015 |
Target sample size:
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428 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005012-42 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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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: 2
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): yes
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Countries of recruitment
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Argentina
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Australia
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Austria
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Belgium
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Brazil
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Bulgaria
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Canada
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Chile
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Denmark
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Estonia
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Finland
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France
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Germany
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Hong Kong
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Hungary
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Israel
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Italy
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Korea, Republic of
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Lithuania
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Mexico
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Netherlands
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New Zealand
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Poland
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Portugal
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Serbia
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Spain
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Sweden
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Switzerland
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Turkey
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United Kingdom
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United States
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Contacts
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Name:
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Project Management
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Address:
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Farnborough Business Park, 1 Pinehurst Road,
GU14 7BF
Farnborough
United Kingdom |
Telephone:
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441276713455 |
Email:
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jewell.jessup@syneoshealth.com |
Affiliation:
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Syneos Health UK Limited |
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Name:
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Project Management
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Address:
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Farnborough Business Park, 1 Pinehurst Road,
GU14 7BF
Farnborough
United Kingdom |
Telephone:
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441276713455 |
Email:
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jewell.jessup@syneoshealth.com |
Affiliation:
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Syneos Health UK Limited |
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Key inclusion & exclusion criteria
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Inclusion criteria: 1. Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Diseases [AASLD] and the European Association for the Study of the Liver [EASL] practice guidelines; Lindor 2009; EASL 2009), as demonstrated by the presence of =2 of the following 3 diagnostic factors: a. History of elevated Alkaline phosphatase levels for at least 6 months. b. Positive antimitochondrial antibody (AMA) titer or if AMA negative or in 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]). c. Liver biopsy consistent with PBC. 2. A mean total bilirubin >ULN and =5x ULN and/or a mean ALP >3x ULN. 3. Either is not taking UDCA (no UDCA dose in the past =3 months) or has been taking UDCA for at least 12 months with a stable dose for =3 months prior to Day 0. 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 278 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria: 1. History or presence of other concomitant liver diseases including: a. Hepatitis C virus infection b. Active hepatitis B infection; however, subjects 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 c. Primary sclerosing cholangitis d. Alcoholic liver disease e. Definite autoimmune liver disease or overlap hepatitis f. Nonalcoholic steatohepatitis g. Gilbert’s Syndrome 2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including: a. History of liver transplant, current placement on a liver transplant list, or current MELD score >12. Subjects who are placed on a transplant list despite a relatively early disease stage (for example per regional guidelines) may be eligible as long as they do not meet any of the other exclusion criteria b. Cirrhosis with complications, including history (within the past 12 months) or presence of: i. Variceal bleeding ii. Uncontrolled ascites iii. Encephalopathy iv. Spontaneous bacterial peritonitis c. Known or suspected hepatocellular carcinoma d. Prior transjugular intrahepatic portosystemic shunt procedure e. Hepatorenal syndrome (type I or II) or Screening (visit 1 or 2) serum creatinine >2 mg/dL (178 µmol/L) 3. Mean total biliburin >5x ULN 4. Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures 5. Other medical conditions that may diminish life expectancy, including known cancers (except carcinomas in situ or other stable, relatively benign conditions) 6. If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating 7. Known history of human immunodeficiency virus infection 8. Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or fractures within 3 months prior to Day 0) 9. Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study 10. History of alcohol abuse or other substance abuse within 1 year prior to Day 0 11. Participation in another investigational product, biologic, or medical device study within 30 days prior to Screening. Participation in a previous study of OCA is allowed with 3 months washout prior to enrollment in this study 12. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain 13. History of known or suspected clinically significant hypersensitivity to OCA or any of its components 14. UDCA naïve (unless contraindicated)
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
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Primary Biliary Cholangitis MedDRA version: 21.0
Level: LLT
Classification code 10036680
Term: Primary biliary cirrhosis
System Organ Class: 100000004871
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Intervention(s)
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Trade Name: Ocaliva Product Name: Obeticholic acid Product Code: OCA, INT-747 Pharmaceutical Form: Tablet INN or Proposed INN: Obeticholic Acid CAS Number: 459789-99-2 Current Sponsor code: 6-ECDCA Other descriptive name: 6a-ethylchenodeoxycholic acid (6-ECDCA), OCA, INT-747 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5- Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use
Trade Name: Ocaliva Product Name: Obeticholic acid Product Code: OCA, INT-747 Pharmaceutical Form: Tablet INN or Proposed INN: Obeticholic Acid CAS Number: 459789-99-2 Current Sponsor code: 6-ECDCA Other descriptive name: 6a-ethylchenodeoxycholic acid (6-ECDCA), OCA, Int-747 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10- Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use
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Primary Outcome(s)
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Main Objective: 1. To assess the effect of OCA compared to placebo, in conjunction with established local standard of care, on clinical outcomes in subjects with PBC as measured by time to first occurrence of any of the following adjudicated events, derived as a composite event endpoint: a. Death (all-cause) b. Liver transplant c. Model of end stage liver disease (MELD) score =15 d. Hospitalization (as defined by a stay of 24 hours or greater) for new onset or recurrence of: i. Variceal bleed ii. Hepatic Encephalopathy (as defined by a West Haven score of =2) iii. Spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis) e. Uncontrolled ascites (diuretic resistant ascites requiring therapeutic paracentesis at a frequency of at least twice in a month)
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Secondary Objective: To assess the effect of OCA compared to placebo on time to first occurrence of each individual component of the primary endpoint as listed above To assess the effect of OCA compared to placebo on time to occurence of liver related death. To assess the effect of OCA compared to placebo on progression to cirrhosis. To assess the effect of OCA compared to placebo on time to occurrence of HCC. To assess the effect of OCA compared to placebo on disease progression via the following: Liver biochemistry Markers of inflammation and fibrosis To assess the effect of OCA compared to historical controls on liver-related clinical outcomes. To characterize the PK of OCA and its conjugates in a subset of subjects. To assess health outcomes and pharmacoeconomics including cost-effectiveness, resource utilization, and quality of life measures in subjects treated with OCA compared to placebo. To assess the safety and tolerability in subjects treated with OCA compared to placebo.
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Primary end point(s): The primary efficacy endpoint will be the time to first occurrence of one of the following post randomization: a. Death (all-cause) b. Liver transplant c. Model of end stage liver disease (MELD) score =15 d. Hospitalization (as defined by a stay of 24 hours or greater) for new onset or recurrence of: i. Variceal bleed ii. Hepatic Encephalopathy (as defined by a West Haven score of =2) iii. Spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis) e. Uncontrolled ascites (diuretic resistant ascites requiring therapeutic paracentesis at a frequency of at least twice in a month)
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Timepoint(s) of evaluation of this end point: 10 years
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Secondary Outcome(s)
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Timepoint(s) of evaluation of this end point: 10 years
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Secondary end point(s): Key Secondary Efficacy Analyses The key secondary efficacy endpoints are as follows: a. Time to first occurrence of MELD score =15 b. Time to liver transplant or death (all-cause) c. Change from Baseline in total bilirubin at end of study d. Change from Baseline in ALP at end of study Other Efficacy Analyses The following time to event secondary efficacy analyses will compare OCA versus placebo using the ITT population: ? Time to each component of the primary efficacy endpoint (except MELD score =15 which is captured above) ? Time to development of varix/varices ? Progression to cirrhosis ? Time to occurrence of HCC ? Time to liver-related death ? Time to liver-related death or liver transplant ? Time to liver-related death, liver transplant, or MELD score =15
Safety Analysis
Safety data, including AEs, AEs of special interst including pruritus and hepatic safety, vitals, electrocardiogram, and clinical laboratory results will be summarized by treatment group for Health outcomes and pharmacokinetic analysis
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Secondary ID(s)
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2014-005012-42-HU
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747-302
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NCT02308111
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Source(s) of Monetary Support
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Intercept Pharmaceuticals Inc.
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Ethics review
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Status: Approved
Approval date: 11/11/2015
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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