Primary Sclerosing CholangitisPhase 3NCT03035058
Efficacy and Safety of Vedolizumab Intravenous (IV) in the Treatment of Primary Sclerosing Cholangitis in Subjects With Underlying Inflammatory Bowel Disease
A Phase 3 study testing Vedolizumab in people with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease, run by Takeda.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of vedolizumab intravenous (IV) in non-end-stage primary sclerosing cholangitis (PSC) participants with underlying inflammatory bowel disease (IBD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Sclerosing Cholangitis, Inflammatory Bowel Disease
- What is being tested?
- Vedolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Feb 2017to Jan 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has chronic cholestatic liver disease, of at least 6 months duration, with a subsequent diagnosis of primary sclerosing cholangitis (PSC), based on cholangiographic findings of intrahepatic and/or extrahepatic bile duct irregularities consistent with PSC.
- Has a diagnosis of inflammatory bowel disease (IBD) (either ulcerative colitis [UC], Crohn's disease [CD], or IBD unclassified [IBDU]), established at least 3 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report.
- Has a liver stiffness transient elastography (TE) score of ≤14.3 kPa, as assessed by FibroScan.
- Has had a colorectal cancer screen within 12 months of the Screening Visit with no signs of malignancy, dysplasia, or neoplasia.
Who cannot join
- Hepatic and Gastrointestinal Exclusion Criteria
- Has received any fibrates within 8 weeks of Screening.
- Has high suspicion of cholangiocarcinoma, as indicated by an elevated Ca 19-9 value (>129 U/mL) at screening.
- Has evidence of overlap syndrome with autoimmune hepatitis or primary or secondary biliary cirrhosis or autoimmune cholangitis, as judged by the investigator.
- Has evidence of alcoholic liver disease including history of alcoholic hepatitis.
- Has a diagnosis of small duct PSC.
Show all 43Show fewer
- Has a Model for End-Stage Liver Disease (MELD) score >12 at screening.
- Has a Child-Pugh score >7 (following adjustment for PSC diagnosis) at screening.
- Has received a liver transplant.
- Has evidence of autoimmune immunoglobin (Ig) IgG4-associated cholangitis, as defined by elevated serum IgG4 at least 2 x ULN (at screening), or IgG4/IgG1 ratio above 0.24.
- Has undergone prior biliary surgery (laparoscopic or open surgery). Participants who have undergone cholecystectomy without surgical complications will be allowed provided the surgery was not done within 6 weeks prior to screening.
- Has had 2 or more interventional treatments for dominant stricture (including stent placement/replacement) within 12 months prior to the Screening Visit.
- Has evidence of cholangitis, requiring antibiotics, within 3 months prior to the Screening Visit [short courses of antibiotics for no more than 5 days are allowed for stent placement or endoscopic retrograde cholangiopancreatography (ERCP) prophylaxis].
- Infectious Disease Exclusion Criteria
- Has chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- Has positive hepatitis B core antibody (anti-HBc) at screening.
- Has evidence of an active infection during the Screening Period.
- Has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
- Has active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:
- History of TB.
- A positive diagnostic TB test within 30 days of enrollment defined as: 1. A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests (or, a positive T-SPOT TB test [Japan only]), OR
- Chest X-ray within 3 months of enrollment in which active or latent pulmonary TB cannot be excluded
- General Exclusion Criteria
- Has had previous exposure to natalizumab, efalizumab, rituximab, or any other integrin antagonist.
- Has received any of the following for the treatment of underlying disease within 30 days of screening:
- Nonbiologic therapies (eg, cyclosporine, tacrolimus, thalidomide) other than those specifically listed in the protocol for the treatment of IBD.
- An approved nonbiologic therapy in an investigational protocol.
- Has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at the Screening Visit.
- Has any history of malignancy, except for the following: (a) adequately treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to randomization; and (c) history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to randomization. Participant with remote history of malignancy (eg, >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis prior to randomization.
- Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating or neurodegenerative disease.
- Has a positive response on the progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of study drug.
- Has received any of the following for the treatment of underlying disease within 30 days of screening:
- Nonbiologic therapies (eg, cyclosporine, tacrolimus, thalidomide) other than those specifically listed in the protocol for the treatment of IBD.
- An approved nonbiologic therapy in an investigational protocol.
- Has had any surgical procedure requiring general anesthesia within 30 days prior to screening or is planning to undergo major surgery during the study.
- Is required to take excluded medications.
- Has received any live vaccinations within 30 days prior to screening.
- Has evidence of or treatment for C. difficile infection within 60 days or other intestinal pathogen within 30 days prior to the Screening Visit or other known infectious, immunologic, or ischemic liver or intestinal disease that, in the investigator's opinion, may interfere with the study procedures or study results.
- Has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at the Screening Visit.
- Has previous history of colectomy.
- In the opinion of the investigator, the participant has a life expectancy or anticipated need for liver transplantation within <24 months.
- Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to screening.
- For the magnetic resonance elastography (MRE) substudy, participants are excluded if they have contraindications to magnetic resonance (MR) scanning. Contraindications include ferromagnetic foreign bodies (eg, shrapnel, ferromagnetic fragments in the orbital area, certain tattoos), certain implanted medical devices (eg, aneurysm clips, cardiac pacemakers) or claustrophobia.
About this study
Official title: A Randomized, Global, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Vedolizumab IV for the Treatment of Primary Sclerosing Cholangitis, With Underlying Inflammatory Bowel Disease
The purpose of this study is to evaluate the efficacy and safety of vedolizumab intravenous (IV) in non-end-stage primary sclerosing cholangitis (PSC) participants with underlying inflammatory bowel disease (IBD).
Read the detailed description
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have non-end-stage primary sclerosing cholangitis (PSC) with underlying inflammatory bowel disease (IBD). This study will look at changes in fibrosis staging in people who take vedolizumab.
The study will enroll approximately 258 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups in ratio 1:1:1-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):
- Vedolizumab 300 mg once every 4 weeks (Q4W)
- Vedolizumab 300 mg once every 8 weeks (Q8W)
- Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient
All participants will be administered vedolizumab or placebo via intravenous infusion
This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 124 weeks. Participants will make multiple visits to the clinic and will be contacted by telephone 6 months after last dose of study drug for a follow-up assessment.
- Being tested
- Vedolizumab, Placebo
- Keywords
- Drug therapy
- Medical subject headings
- Cholangitis, Sclerosing, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VedolizumabDrug
Also called MLN0002, ENTYVIO, KYNTELES
Vedolizumab intravenous infusion
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Vedolizumab IV 300 mg Q4W | Experimental | Vedolizumab 300 mg, intravenous (IV), once at Day 1 and Week 2; followed by vedolizumab 300 mg, IV, once every 4 weeks (Q4W) starting from Week 6 to Week 102. Receives: Drug: Vedolizumab |
| Vedolizumab IV 300 mg Q8W + Placebo | Experimental | Vedolizumab 300 mg, IV, once at Day 1 and Week 2; followed by vedolizumab 300 mg, IV, once every 8 weeks (Q8W) starting from Week 6 to Week 102 (and placebo, IV, Q8W starting from Week 10 to Week 98. Receives: Drug: Vedolizumab; Drug: Placebo |
| Placebo | Placebo comparator | Vedolizumab placebo-matching, IV, at Day 1 and Week 2; followed by Vedolizumab placebo-matching, IV, Q4W starting from Week 6 to Week 102. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with No Worsening in Ishak Fibrosis Staging Score from Baseline to Week 106 Visit
Assessments will be performed from liver biopsies with histology assessed by 2 independent blinded central readers for Ishak fibrosis staging score. Ishak fibrosis staging scoring is as follows: 0=No fibrosis, 1=Fibrous expansion of some portal areas with or without septa, 2=Fibrous expansion of most portal areas with or without septa, 3=Fibrous expansion of most portal areas with occasional portal to portal bridging, 4=Fibrous expansion of portal areas with marked bridging (portal to portal and/or portal to central), 5=Marked bridging with occasional nodules (incomplete cirrhosis), 6=Cirrhosis, probable or definitive. A negative change from Baseline indicates improvement.
Measured: Baseline and Week 106
Secondary outcomes (2)
Percentage of Participants with a ≥35% Reduction in Serum Alkaline Phosphatase (ALP) from Baseline to Week 106 Visit
Blood will be collected and ALP will be assessed as part of the serum chemistry testing.
Measured: Baseline and Week 106
Change in Ishak Necroinflammatory Grading Score from Baseline to the Week 106 Visit
Assessments will be performed from liver biopsies with histology assessed by 2 independent blinded central readers for Ishak fibrosis staging score. Ishak necroinflammatory grading score is based on assessments from 4 subscales: (A) Periportal or periseptal interface hepatitis (piecemeal necrosis) 5-point subscale (0=Absent to 4=Severe), (B) Confluent necrosis 7-point subscale (0=Absent to 6=Panacinar or multiacinar necrosis), (C) Focal (spotty) lytic necrosis, apoptosis and focal inflammation 5-point subscale (0=Absent to 4=More than ten foci per times 10 objective), and (D) Portal inflammation (0=Absent to 4=Marked, all portal areas). A negative change from Baseline indicates improvement.
Measured: Baseline and Week 106
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2017 (estimated)
- Study startFeb 2017
- Primary completionSep 2020 (estimated)
- Study completionJan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Sclerosing CholangitisStudies of the same condition, open and under way.
- More trials run by TakedaThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03035058
- Sponsor's protocol ID
- MLN0002-3023
- Other IDs
- 2014-003942-28, U1111-1161-4900, 16/LO/0288, NL56650.056.16, 191059, 2014
- Status last verified
- Mar 2017
- First submitted
- 25 Jan 2017
- Last updated
- 8 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Global, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Vedolizumab IV for the Treatment of Primary Sclerosing Cholangitis, With Underlying Inflammatory Bowel Disease
- ClinicalTrials.gov ID
- NCT03035058
- Acronym / sponsor ID
- MLN0002-3023
- Keywords
- Drug therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Feb 2017
- Primary completion
- Sep 2020 (estimated)
- Study completion
- Jan 2021 (estimated)
- First posted
- 27 Jan 2017 (estimated)
- Results
- Not posted in the source record
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 vedolizumab intravenous (IV) in non-end-stage primary sclerosing cholangitis (PSC) participants with underlying inflammatory bowel disease (IBD).
Detailed description
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have non-end-stage primary sclerosing cholangitis (PSC) with underlying inflammatory bowel disease (IBD). This study will look at changes in fibrosis staging in people who take vedolizumab.
The study will enroll approximately 258 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups in ratio 1:1:1-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):
- Vedolizumab 300 mg once every 4 weeks (Q4W)
- Vedolizumab 300 mg once every 8 weeks (Q8W)
- Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient
All participants will be administered vedolizumab or placebo via intravenous infusion
This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 124 weeks. Participants will make multiple visits to the clinic and will be contacted by telephone 6 months after last dose of study drug for a follow-up assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Vedolizumab IV 300 mg Q4W | Experimental | Drug: VedolizumabVedolizumab 300 mg, intravenous (IV), once at Day 1 and Week 2; followed by vedolizumab 300 mg, IV, once every 4 weeks (Q4W) starting from Week 6 to Week 102. |
| Vedolizumab IV 300 mg Q8W + Placebo | Experimental | Drug: Vedolizumab, Drug: PlaceboVedolizumab 300 mg, IV, once at Day 1 and Week 2; followed by vedolizumab 300 mg, IV, once every 8 weeks (Q8W) starting from Week 6 to Week 102 (and placebo, IV, Q8W starting from Week 10 to Week 98. |
| Placebo | Placebo comparator | Drug: PlaceboVedolizumab placebo-matching, IV, at Day 1 and Week 2; followed by Vedolizumab placebo-matching, IV, Q4W starting from Week 6 to Week 102. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Has chronic cholestatic liver disease, of at least 6 months duration, with a subsequent diagnosis of primary sclerosing cholangitis (PSC), based on cholangiographic findings of intrahepatic and/or extrahepatic bile duct irregularities consistent with PSC.
- Has a diagnosis of inflammatory bowel disease (IBD) (either ulcerative colitis [UC], Crohn's disease [CD], or IBD unclassified [IBDU]), established at least 3 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report.
- Has a liver stiffness transient elastography (TE) score of ≤14.3 kPa, as assessed by FibroScan.
- Has had a colorectal cancer screen within 12 months of the Screening Visit with no signs of malignancy, dysplasia, or neoplasia.
Key exclusion criteria (43 listed)
- Hepatic and Gastrointestinal Exclusion Criteria
- Has received any fibrates within 8 weeks of Screening.
- Has high suspicion of cholangiocarcinoma, as indicated by an elevated Ca 19-9 value (>129 U/mL) at screening.
- Has evidence of overlap syndrome with autoimmune hepatitis or primary or secondary biliary cirrhosis or autoimmune cholangitis, as judged by the investigator.
- Has evidence of alcoholic liver disease including history of alcoholic hepatitis.
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 |
|---|---|---|
| VedolizumabAlso: MLN0002, ENTYVIO, KYNTELESVedolizumab intravenous infusion | Drug | Vedolizumab IV 300 mg Q4W, Vedolizumab IV 300 mg Q8W + Placebo |
| PlaceboPlacebo | Drug | Placebo, Vedolizumab IV 300 mg Q8W + Placebo |
Primary outcome
Percentage of Participants with No Worsening in Ishak Fibrosis Staging Score from Baseline to Week 106 Visit
Time frame: Baseline and Week 106
Assessments will be performed from liver biopsies with histology assessed by 2 independent blinded central readers for Ishak fibrosis staging score. Ishak fibrosis staging scoring is as follows: 0=No fibrosis, 1=Fibrous expansion of some portal areas with or without septa, 2=Fibrous expansion of most portal areas with or without septa, 3=Fibrous expansion of most portal areas with occasional portal to portal bridging, 4=Fibrous expansion of portal areas with marked bridging (portal to portal and/or portal to central), 5=Marked bridging with occasional nodules (incomplete cirrhosis), 6=Cirrhosis, probable or definitive. A negative change from Baseline indicates improvement.
2 secondary outcomes
Percentage of Participants with a ≥35% Reduction in Serum Alkaline Phosphatase (ALP) from Baseline to Week 106 Visit
Time frame: Baseline and Week 106
Change in Ishak Necroinflammatory Grading Score from Baseline to the Week 106 Visit
Time frame: Baseline and Week 106
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2017.
Related trials for Primary Sclerosing Cholangitis
RecruitingObservational study
Unraveling the Mechanisms Underlying Primary Sclerosing Cholangitis Through a Multidisciplinary, Integrative Research Approach
Primary Sclerosing Cholangitis
Not yet recruitingPhase 2
FEAST and HOPE: Redox PSC Pilot Study
Primary Sclerosing Cholangitis (PSC)
RecruitingPhase 3
A Study to Assess How Well and Safely Elafibranor Works in Adult Participants With Primary Sclerosing Cholangitis
Primary Sclerosing Cholangitis
Active, not recruitingPhase 2
A Study to Assess Safety and Effectiveness of Elafibranor in Adult Participants With Primary Sclerosing Cholangitis.
Primary Sclerosing Cholangitis
Active, not recruitingPhase 2
A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (PSC)
Primary Sclerosing 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.
Medical Director Clinical Science study director
Takeda
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vedolizumab in people with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease, run by Takeda.
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 4 inclusion and 43 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: withdrawn, as of the sponsor's last update on 8 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Percentage of Participants with No Worsening in Ishak Fibrosis Staging Score from Baseline to Week 106 Visit (time frame: Baseline and Week 106). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Mar 2017.