Liver Cirrhosis, BiliaryPhase 2NCT00570765
Study of INT-747 as Monotherapy in Participants With Primary Biliary Cirrhosis (PBC)
A Phase 2 study testing Obeticholic Acid (OCA) in people with Liver Cirrhosis, Biliary, run by Intercept Pharmaceuticals at 21 sites in 7 countries.
Trial summary
The primary hypothesis was that obeticholic acid (OCA) will cause a reduction in alkaline phosphatase levels in PBC participants, over a 12-week treatment period, as compared to placebo. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Cirrhosis, Biliary
- What is being tested?
- Obeticholic Acid (OCA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 21 sitesin 7 countries
- Study dates
- 17 Jan 2008to 25 Sep 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female participants must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use 1 effective method of contraception with all sexual partners during the study and for 14 days after the end of dosing.
- Male participants must be prepared to use 1 effective method of contraception with all sexual partners during the study during the study unless they had a prior vasectomy.
- Proven or likely PBC, as demonstrated by the participant presenting with at least 2 of the following 3 diagnostic factors:
- History of increased alkaline phosphatase (ALP) levels for at least 6 months;
- Positive antimitochondrial antibody titer (>1:40 titer on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive);
- Liver biopsy consistent with PBC
- Screening ALP level between 1.5 and 10 × upper limit of normal (ULN).
Who cannot join
- Administration of the following drugs at any time during the 3 months prior to screening for the study: ursodeoxycholic acid, colchicine, methotrexate, azathioprine, or systemic corticosteroids.
- Screening conjugated (direct) bilirubin >2 × ULN.
- Screening alanine aminotransferase or aspartate aminotransferase >5 × ULN.
- Screening serum creatinine >133 micromoles/liter (1.5 mg/deciliter).
- History or presence of hepatic decompensation (for example, variceal bleeds, encephalopathy, or poorly controlled ascites).
- History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus infection, primary sclerosing cholangitis, alcoholic liver disease, definite autoimmune liver disease or biopsy proven nonalcoholic steatohepatitis.
- Pregnancy.
Trial locations and contacts
21 sites in 7 countries.
21 sites in 7 countries
United Kingdom6 sites
Queen Elizabeth Medical Center
Edgbaston, Birmingham, B15 2TH
Royal Infirmary
Edinburgh, EH16 4SA
Royal Free Hospital
Hampstead, London, NW3 2QG
John Radcliffe Hospital
Headington, Oxford, OX3 9DU
Sunderland Research Ethics Committee
Jarrow, NE32 3DT
University Upon Tyne/Newcastle
Newcastle upon Tyne, NE2 4HH
United States4 sites
Henry Ford
Detroit, Michigan, 48202
Baylor College of Medicine
Houston, Texas, 77030
Virginia Commonwealth University
Richmond, Virginia, 23298
Virginia Mason Medical Center
Seattle, Washington, 98105
Germany4 sites
Johann Wolfgang Goethe University
Frankfurt, 60590
University Medical Centre Hamburg-Eppendorf
Hamburg, 20246
Medical School of Hannover
Hanover, 30625
University of Munich
Munich, 81377
Canada3 sites
University of Alberta
Edmonton, Alberta, T6G 1K8
Centre de Recherche du CHUM / University of Montreal
Montreal, Quebec, H2L 3R4
University of Toronto
Toronto, Ontario, M5T 1S8
France2 sites
Hopital de l'Hotel Dieu
Lyon, 69288
Hopital Saint-Antoine
Paris, 75012
About this study
Official title: A Study of INT-747 (6-ECDCA) Monotherapy in Patients With Primary Biliary Cirrhosis
The primary hypothesis was that obeticholic acid (OCA) will cause a reduction in alkaline phosphatase levels in PBC participants, over a 12-week treatment period, as compared to placebo.
Read the detailed description
The study included 2 phases: a 3-month randomized, double-blind (DB), placebo-controlled, parallel group phase, followed by a long-term safety extension (LTSE). The planned duration of the LTSE phase was country-specific, ranging from 108 months to indefinitely. On-site visits occurred at least every 6 months.
Following completion of the 3-month DB phase, participants who continued to meet protocol requirements were given the opportunity to enroll in the LTSE phase of the study at selected study sites. The participants who enrolled in the LTSE phase started OCA administration, from a starting dose (10 or 50 milligrams [mg]) based on the dose of OCA or placebo received in the DB phase or on the timing of entry into the LTSE phase.
Because the LTSE phase was not planned in the original study design, participants had varied gaps between the end of the DB phase and the start of the LTSE phase. Moreover, some participants initiated ursodeoxycholic acid during the course of that break.
- Conditions
- Liver Cirrhosis, Biliary
- Being tested
- Placebo, Obeticholic Acid (OCA)
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Matching placebo tablets were administered orally once daily.
Obeticholic Acid (OCA)Drug
Also called INT-747, 6α-ethyl-chenodeoxycholic acid (6-ECDCA)
Starting dose of 10 or 50 mg administered orally once daily, followed by dose titration planned from 10 mg to 25 mg to 50 mg once daily, which could be modified for safety and tolerability issues or to achieve adequate therapeutic response.
| Study group | Role | What they receive |
|---|---|---|
| DB OCA 10 mg | Experimental | OCA 10 mg for 3 months during the DB phase. Receives: Drug: Obeticholic Acid (OCA) |
| DB OCA 50 mg | Experimental | OCA 50 mg for 3 months during the DB phase. Receives: Drug: Obeticholic Acid (OCA) |
| DB OCA Placebo | Placebo comparator | Matching placebo for 3 months during the DB phase. Receives: Drug: Placebo |
| LTSE OCA Total | Experimental | After completion of the 3-month DB phase, all eligible participants were offered the opportunity to enter an open-label LTSE for up to 96 months beginning at 10 mg OCA. Doses up to 50 mg daily were evaluated. Receives: Drug: Obeticholic Acid (OCA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
DB Phase: Mean Percent Change In Serum Alkaline Phosphatase (ALP) From Baseline To Day 85
The percent change in serum ALP from baseline to Day 85 is reported. The baseline value used was the mean of the pretreatment Screening and Day 0 evaluations.
Measured: Baseline, Day 85
Secondary outcomes (14)
DB Phase: Mean Percent Change In Gamma-glutamyl Transferase (GGT) From Baseline To Day 85
As a marker of hepatocellular injury and liver function, the percent change in GGT from baseline to Day 85 is reported.
Measured: Baseline, Day 85
DB Phase: Mean Percent Change In Alanine Transaminase (ALT) From Baseline To Day 85
As a marker of hepatocellular injury and liver function, the percent change in ALT from baseline to Day 85 is reported.
Measured: Baseline, Day 85
DB: Plasma Trough Concentrations Of OCA And Its Major, Known Metabolites
Measured: 12 weeks
DB Phase: Mean Percent Change In Conjugated Bilirubin From Baseline To Day 85
As a marker of hepatocellular injury and liver function, the percent change in conjugated bilirubin from baseline to Day 85 is reported.
Measured: Baseline, Day 85
LTSE Phase: Median Percent Change In Serum ALP From Baseline To Month 24, Month 48, Month 72, And Last Available Visit
The percent change in serum ALP from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Month 24, Month 48, Month 72, Last Available Visit (up to 96 months)
LTSE Phase: Mean Percent Change In Serum ALP From Baseline To Month 24, Month 48, Month 72, And Last Available Visit
The percent change in serum ALP from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Month 24, Month 48, Month 72, Last Available Visit (up to 96 months)
LTSE: Median Percent Change In GGT From Baseline To Last Available Visit
As a marker of hepatocellular injury and liver function, the percent change in GGT from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Mean Percent Change In GGT From Baseline To Last Available Visit
As a marker of hepatocellular injury and liver function, the percent change in GGT from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Median Percent Change In ALT From Baseline To Last Available Visit
As a marker of hepatocellular injury and liver function, the percent change in ALT from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Mean Percent Change In ALT From Baseline To Last Available Visit
As a marker of hepatocellular injury and liver function, the percent change in ALT from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Median Percent Change In Conjugated Bilirubin From Baseline To Last Available Visit
As a marker of hepatocellular injury and liver function, the percent change in conjugated bilirubin from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Mean Percent Change In Conjugated Bilirubin From Baseline To Last Available Visit
As a marker of hepatocellular injury and liver function, the percent change in conjugated bilirubin from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Median Percent Change In Total Bilirubin From Baseline To Last Available Visit
As a marker of hepatocellular injury and liver function, the percent change in total bilirubin from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Mean Percent Change In Total Bilirubin From Baseline To Last Available Visit
As a marker of hepatocellular injury and liver function, the percent change in total bilirubin from baseline to the last available visit is reported. The DB baseline value was used as the baseline.
Measured: Baseline (DB), Last Available Visit (up to 96 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2007 (estimated)
- Study start17 Jan 2008
- Primary completion21 Sep 2010
- Study completion25 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver Cirrhosis, BiliaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intercept Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christian Weyer, MD, Study chair, Intercept Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00570765
- Sponsor's protocol ID
- 747-201
- Other IDs
- 2007-001424-12
- Status last verified
- May 2021
- First submitted
- 7 Dec 2007
- Last updated
- 22 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kowdley KV, Luketic V, Chapman R, Hirschfield GM, Poupon R, Schramm C, Vincent C, Rust C, Pares A, Mason A, Marschall HU, Shapiro D, Adorini L, Sciacca C, Beecher-Jones T, Bohm O, Pencek R, Jones D; Obeticholic Acid PBC Monotherapy Study Group. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis. Hepatology. 2018 May;67(5):1890-1902. doi: 10.1002/hep.29569. Epub 2018 Jan 29.
PubMed 29023915
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of INT-747 (6-ECDCA) Monotherapy in Patients With Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT00570765
- Acronym / sponsor ID
- 747-201
- Conditions
- Liver Cirrhosis, Biliary
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Intercept PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 17 Jan 2008 (actual)
- Primary completion
- 21 Sep 2010 (actual)
- Study completion
- 25 Sep 2017 (actual)
- First posted
- 11 Dec 2007 (estimated)
- Results
- Posted 7 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary hypothesis was that obeticholic acid (OCA) will cause a reduction in alkaline phosphatase levels in PBC participants, over a 12-week treatment period, as compared to placebo.
Detailed description
The study included 2 phases: a 3-month randomized, double-blind (DB), placebo-controlled, parallel group phase, followed by a long-term safety extension (LTSE). The planned duration of the LTSE phase was country-specific, ranging from 108 months to indefinitely. On-site visits occurred at least every 6 months.
Following completion of the 3-month DB phase, participants who continued to meet protocol requirements were given the opportunity to enroll in the LTSE phase of the study at selected study sites. The participants who enrolled in the LTSE phase started OCA administration, from a starting dose (10 or 50 milligrams [mg]) based on the dose of OCA or placebo received in the DB phase or on the timing of entry into the LTSE phase.
Because the LTSE phase was not planned in the original study design, participants had varied gaps between the end of the DB phase and the start of the LTSE phase. Moreover, some participants initiated ursodeoxycholic acid during the course of that break.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| DB OCA 10 mg | Experimental | Drug: Obeticholic Acid (OCA)OCA 10 mg for 3 months during the DB phase. |
| DB OCA 50 mg | Experimental | Drug: Obeticholic Acid (OCA)OCA 50 mg for 3 months during the DB phase. |
| DB OCA Placebo | Placebo comparator | Drug: PlaceboMatching placebo for 3 months during the DB phase. |
| LTSE OCA Total | Experimental | Drug: Obeticholic Acid (OCA)After completion of the 3-month DB phase, all eligible participants were offered the opportunity to enter an open-label LTSE for up to 96 months beginning at 10 mg OCA. Doses up to 50 mg daily were evaluated. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Female participants must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use 1 effective method of contraception with all sexual partners during the study and for 14 days after the end of dosing.
- Male participants must be prepared to use 1 effective method of contraception with all sexual partners during the study during the study unless they had a prior vasectomy.
- Proven or likely PBC, as demonstrated by the participant presenting with at least 2 of the following 3 diagnostic factors:
- History of increased alkaline phosphatase (ALP) levels for at least 6 months;
- Positive antimitochondrial antibody titer (>1:40 titer on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive);
Key exclusion criteria (7 listed)
- Administration of the following drugs at any time during the 3 months prior to screening for the study: ursodeoxycholic acid, colchicine, methotrexate, azathioprine, or systemic corticosteroids.
- Screening conjugated (direct) bilirubin >2 × ULN.
- Screening alanine aminotransferase or aspartate aminotransferase >5 × ULN.
- Screening serum creatinine >133 micromoles/liter (1.5 mg/deciliter).
- History or presence of hepatic decompensation (for example, variceal bleeds, encephalopathy, or poorly controlled ascites).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboMatching placebo tablets were administered orally once daily. | Drug | DB OCA Placebo |
| Obeticholic Acid (OCA)Also: INT-747, 6α-ethyl-chenodeoxycholic acid (6-ECDCA)Starting dose of 10 or 50 mg administered orally once daily, followed by dose titration planned from 10 mg to 25 mg to 50 mg once daily, which could be modified for safety and tolerability issues or to achieve adequate therapeutic response. | Drug | DB OCA 10 mg, DB OCA 50 mg, LTSE OCA Total |
Primary outcome
DB Phase: Mean Percent Change In Serum Alkaline Phosphatase (ALP) From Baseline To Day 85
Time frame: Baseline, Day 85
The percent change in serum ALP from baseline to Day 85 is reported. The baseline value used was the mean of the pretreatment Screening and Day 0 evaluations.
14 secondary outcomes
DB Phase: Mean Percent Change In Gamma-glutamyl Transferase (GGT) From Baseline To Day 85
Time frame: Baseline, Day 85
DB Phase: Mean Percent Change In Alanine Transaminase (ALT) From Baseline To Day 85
Time frame: Baseline, Day 85
DB: Plasma Trough Concentrations Of OCA And Its Major, Known Metabolites
Time frame: 12 weeks
DB Phase: Mean Percent Change In Conjugated Bilirubin From Baseline To Day 85
Time frame: Baseline, Day 85
LTSE Phase: Median Percent Change In Serum ALP From Baseline To Month 24, Month 48, Month 72, And Last Available Visit
Time frame: Baseline (DB), Month 24, Month 48, Month 72, Last Available Visit (up to 96 months)
LTSE Phase: Mean Percent Change In Serum ALP From Baseline To Month 24, Month 48, Month 72, And Last Available Visit
Time frame: Baseline (DB), Month 24, Month 48, Month 72, Last Available Visit (up to 96 months)
LTSE: Median Percent Change In GGT From Baseline To Last Available Visit
Time frame: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Mean Percent Change In GGT From Baseline To Last Available Visit
Time frame: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Median Percent Change In ALT From Baseline To Last Available Visit
Time frame: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Mean Percent Change In ALT From Baseline To Last Available Visit
Time frame: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Median Percent Change In Conjugated Bilirubin From Baseline To Last Available Visit
Time frame: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Mean Percent Change In Conjugated Bilirubin From Baseline To Last Available Visit
Time frame: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Median Percent Change In Total Bilirubin From Baseline To Last Available Visit
Time frame: Baseline (DB), Last Available Visit (up to 96 months)
LTSE: Mean Percent Change In Total Bilirubin From Baseline To Last Available Visit
Time frame: Baseline (DB), Last Available Visit (up to 96 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29023915Kowdley KV, Luketic V, Chapman R, Hirschfield GM, Poupon R, Schramm C, Vincent C, Rust C, Pares A, Mason A, Marschall HU, Shapiro D, Adorini L, Sciacca C, Beecher-Jones T, Bohm O, Pencek R, Jones D; Obeticholic Acid PBC Monotherapy Study Group. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis. Hepatology. 2018 May;67(5):1890-1902. doi: 10.1002/hep.29569. Epub 2018 Jan 29.
Related trials for Liver Cirrhosis, Biliary
Active, not recruitingPhase 3
Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cirrhosis
RecruitingPhase 3
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis
Primary Biliary Cholangitis
RecruitingPhase 3
FIREFLY Trial: Fenofibrate Intervention---Randomized Evaluation in First-Line PBC Therapy
Primary Biliary Cholangitis (PBC)
RecruitingPhase 3
Fenofibrate for Patients With Primary Biliary Cirrhosis Who Had An Inadequate Response to Ursodeoxycholic Acid
Primary Biliary Cirrhosis
RecruitingPhase 2/3
Fenofibrate in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cholangitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Weyer, MD study chair
Intercept Pharmaceuticals, Inc.
21 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Obeticholic Acid (OCA) in people with Liver Cirrhosis, Biliary, run by Intercept Pharmaceuticals at 21 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United Kingdom, United States, Germany, Canada, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DB Phase: Mean Percent Change In Serum Alkaline Phosphatase (ALP) From Baseline To Day 85 (time frame: Baseline, Day 85). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00570765, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2021.