Primary Biliary CirrhosisPhase 2NCT01389973
A Study of Efficacy and Safety of Ustekinumab in Patients With Primary Biliary Cirrhosis (PBC) Who Had an Inadequate Response to Ursodeoxycholic Acid
A Phase 2 study testing ustekinumab 90 mg, ustekinumab 45 mg and ustekinumab 180 mg in people with Primary Biliary Cirrhosis, run by Janssen Research & Development, LLC at 10 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of ustekinumab in patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- ustekinumab 90 mg, ustekinumab 45 mg and ustekinumab 180 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Sep 2011to Jun 2013
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have proven or are likely to have Primary Biliary Cirrhosis (PBC)
- Be on a stable dose of ursodeoxycholic acid for at least 6 months prior to Week 0
- Have screening alkaline phosphatase (ALP) level > 1.67 ULN (the upper limit of normal)
- Have screening laboratory test results within protocol-specified limits
- Have no history of latent or active tuberculosis (TB) prior to screening and no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
Who cannot join
- Has history of gastrointestinal bleeding, secondary to portal hypertension, hepatic encephalopathy, or ascites requiring treatment with diuretics
- Has a screening direct bilirubin > 1.0 mg/dL
- Has a previous liver histology with a diagnosis of steatohepatitis or has a high risk of nonalcoholic steatohepatitis
- Has a previous liver histology with a diagnosis of chronic autoimmune hepatitis or has a high risk of autoimmune hepatitis overlap syndrome
- Testing positive for surface antigen (HBsAg+), regardless of the results of other hepatitis B tests
- Have used colchicine, methotrexate (MTX), azathioprine (AZA), or systemic corticosteroids within 3 months prior to the first administration of study drug.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States6 sites
Study site
Houston, Texas
Study site
Jacksonville, Florida
Study site
Miami, Florida
Study site
Naples, Florida
Study site
New York, New York
Study site
Tupelo, Mississippi
Canada4 sites
Study site
Halifax, Nova Scotia
Study site
Montreal, Quebec
Study site
Toronto, Ontario
Study site
Vancouver, British Columbia
About this study
Official title: A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Evaluating the Efficacy and Safety of Ustekinumab in Subjects With Primary Biliary Cirrhosis Who Had an Inadequate Response to Ursodeoxycholic Acid (UDCA)
The purpose of this study is to evaluate the efficacy and safety of ustekinumab in patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid.
Read the detailed description
This is a multi-center, randomized (treatment will be assigned by chance), placebo-controlled (an inactive substance will be compared with the test drug to see whether the drug has a real effect), parallel-group (two or more groups of patients will receive different treatments) study that will consist of two parts. Part 1 will be an open-label (all participants will know the identity of the treatment) proof-of-concept study. Part 2 will be contingent on the results of Part 1 and will be double-blind (investigators and patients will not know what treatment is being given) and will evaluate the efficacy and safety of ustekinumab in patients with primary biliary cirrhosis (PBC) who had an inadequate response to ursodeoxycholic acid. The duration of participation in the study for an individual participant may be up to 216 weeks. Patient safety will be monitored. Part 1: ustekinumab, 90mg subcutaneous (SC) at Weeks 0 and 4 and every 8 weeks through Week 20; Part 2: Depending on Part 1 results, either (ustekinumab 90mg or 45mg or placebo) or (ustekinumab 90mg or 180mg or placebo) SC at Weeks 0 and 4 and every 8 weeks through Week 20; Long-term Extension (including Part 1 and Part 2): beginning at Week 28, every 8 weeks with initially assigned dose until the extension dose has been selected; then every 8 weeks through Week 196 with the selected dose.
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- ustekinumab 90 mg, ustekinumab 45 mg, ustekinumab 180 mg, Placebo
- Keywords
- Diseases [C] - Digestive System Diseases [C06], primary biliary cirrhosis, ursodeoxycholic acid (UDCA), STELARA, ustekinumab
- 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.
ustekinumab 90 mgDrug
Subcutaneous injections of ustekinumb 90 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.
ustekinumab 45 mgDrug
Subcutaneous injections of ustekinumb 45 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.
ustekinumab 180 mgDrug
Subcutaneous injections of ustekinumb 180 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.
PlaceboDrug
Subcutaneous injections of placebo at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.
| Study group | Role | What they receive |
|---|---|---|
| Open-label: ustekinumab 90 mg | Experimental | Not described Receives: Drug: ustekinumab 90 mg |
| Double-blind: ustekinumab 45 mg | Experimental | Not described Receives: Drug: ustekinumab 45 mg |
| Double-blind: ustekinumab 90 mg | Experimental | Not described Receives: Drug: ustekinumab 90 mg |
| Double-blind: ustekinumb 180 mg | Experimental | Not described Receives: Drug: ustekinumab 180 mg |
| Double-blind: placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Alkaline Phosphatase (ALP) Response at Week 12
The ALP response was defined as a greater than 40 percent (%) decrease from Baseline in ALP concentration at Week 12.
Measured: Week 12
Secondary outcomes (4)
Part 1: Number of Participants With ALP Response at Week 28
Measured: Week 28
Part 1: Number of Participants With ALP Remission at Week 28
ALP remission is defined as either normalization of ALP (for participants with baseline ALP between 1.67*and 2.8* upper limit of normal [ULN] or an ALP less than [˂]1.67*ULN [for participants with baseline ALP greater than {˃} 2.8* ULN]). ALP levels above 1.67* ULN level were associated with an increased rate of disease progression.
Measured: Week 28
Part 1: Percent Change From Baseline in ALP Concentration at Week 28
Measured: Baseline and Week 28
Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28
Measured: Baseline and Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2011 (estimated)
- Study startSep 2011
- Primary completionJun 2013
- Study completionJun 2013
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 Primary Biliary CirrhosisStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01389973
- Sponsor's protocol ID
- CR018748
- Other IDs
- CNTO1275PBC2001, 2011-000554-31
- Status last verified
- Jun 2016
- First submitted
- 7 Jul 2011
- Last updated
- 20 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Mousa HS, Lleo A, Invernizzi P, Bowlus CL, Gershwin ME. Advances in pharmacotherapy for primary biliary cirrhosis. Expert Opin Pharmacother. 2015 Apr;16(5):633-43. doi: 10.1517/14656566.2015.998650. Epub 2014 Dec 29.
PubMed 25543678
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Evaluating the Efficacy and Safety of Ustekinumab in Subjects With Primary Biliary Cirrhosis Who Had an Inadequate Response to Ursodeoxycholic Acid (UDCA)
- ClinicalTrials.gov ID
- NCT01389973
- Acronym / sponsor ID
- CR018748
- Conditions
- Primary Biliary Cirrhosis
- Keywords
- Diseases [C] - Digestive System Diseases [C06], primary biliary cirrhosis, ursodeoxycholic acid (UDCA), STELARA, ustekinumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 8 Jul 2011 (estimated)
- Results
- Posted 15 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of ustekinumab in patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid.
Detailed description
This is a multi-center, randomized (treatment will be assigned by chance), placebo-controlled (an inactive substance will be compared with the test drug to see whether the drug has a real effect), parallel-group (two or more groups of patients will receive different treatments) study that will consist of two parts. Part 1 will be an open-label (all participants will know the identity of the treatment) proof-of-concept study. Part 2 will be contingent on the results of Part 1 and will be double-blind (investigators and patients will not know what treatment is being given) and will evaluate the efficacy and safety of ustekinumab in patients with primary biliary cirrhosis (PBC) who had an inadequate response to ursodeoxycholic acid. The duration of participation in the study for an individual participant may be up to 216 weeks. Patient safety will be monitored. Part 1: ustekinumab, 90mg subcutaneous (SC) at Weeks 0 and 4 and every 8 weeks through Week 20; Part 2: Depending on Part 1 results, either (ustekinumab 90mg or 45mg or placebo) or (ustekinumab 90mg or 180mg or placebo) SC at Weeks 0 and 4 and every 8 weeks through Week 20; Long-term Extension (including Part 1 and Part 2): beginning at Week 28, every 8 weeks with initially assigned dose until the extension dose has been selected; then every 8 weeks through Week 196 with the selected dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Open-label: ustekinumab 90 mg | Experimental | Drug: ustekinumab 90 mg |
| Double-blind: ustekinumab 45 mg | Experimental | Drug: ustekinumab 45 mg |
| Double-blind: ustekinumab 90 mg | Experimental | Drug: ustekinumab 90 mg |
| Double-blind: ustekinumb 180 mg | Experimental | Drug: ustekinumab 180 mg |
| Double-blind: placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Have proven or are likely to have Primary Biliary Cirrhosis (PBC)
- Be on a stable dose of ursodeoxycholic acid for at least 6 months prior to Week 0
- Have screening alkaline phosphatase (ALP) level > 1.67 ULN (the upper limit of normal)
- Have screening laboratory test results within protocol-specified limits
- Have no history of latent or active tuberculosis (TB) prior to screening and no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
Key exclusion criteria (6 listed)
- Has history of gastrointestinal bleeding, secondary to portal hypertension, hepatic encephalopathy, or ascites requiring treatment with diuretics
- Has a screening direct bilirubin > 1.0 mg/dL
- Has a previous liver histology with a diagnosis of steatohepatitis or has a high risk of nonalcoholic steatohepatitis
- Has a previous liver histology with a diagnosis of chronic autoimmune hepatitis or has a high risk of autoimmune hepatitis overlap syndrome
- Testing positive for surface antigen (HBsAg+), regardless of the results of other hepatitis B tests
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 |
|---|---|---|
| ustekinumab 90 mgSubcutaneous injections of ustekinumb 90 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose. | Drug | Double-blind: ustekinumab 90 mg, Open-label: ustekinumab 90 mg |
| ustekinumab 45 mgSubcutaneous injections of ustekinumb 45 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose. | Drug | Double-blind: ustekinumab 45 mg |
| ustekinumab 180 mgSubcutaneous injections of ustekinumb 180 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose. | Drug | Double-blind: ustekinumb 180 mg |
| PlaceboSubcutaneous injections of placebo at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose. | Drug | Double-blind: placebo |
Primary outcome
Part 1: Number of Participants With Alkaline Phosphatase (ALP) Response at Week 12
Time frame: Week 12
The ALP response was defined as a greater than 40 percent (%) decrease from Baseline in ALP concentration at Week 12.
4 secondary outcomes
Part 1: Number of Participants With ALP Response at Week 28
Time frame: Week 28
Part 1: Number of Participants With ALP Remission at Week 28
Time frame: Week 28
Part 1: Percent Change From Baseline in ALP Concentration at Week 28
Time frame: Baseline and Week 28
Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28
Time frame: Baseline and Week 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25543678Mousa HS, Lleo A, Invernizzi P, Bowlus CL, Gershwin ME. Advances in pharmacotherapy for primary biliary cirrhosis. Expert Opin Pharmacother. 2015 Apr;16(5):633-43. doi: 10.1517/14656566.2015.998650. Epub 2014 Dec 29.
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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.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ustekinumab 90 mg, ustekinumab 45 mg and ustekinumab 180 mg in people with Primary Biliary Cirrhosis, run by Janssen Research & Development, LLC at 10 sites in 2 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 5 inclusion and 6 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 20 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Canada. 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 15 Oct 2014). 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?
Part 1: Number of Participants With Alkaline Phosphatase (ALP) Response at Week 12 (time frame: Week 12). 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 NCT01389973, 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 20 Jun 2016.