Hepatic CirrhosisPhase 2NCT03420768
A Study of Experimental Medication BMS-986263 in Adults With Advanced Hepatic Fibrosis After Cure of Hepatitis C
A Phase 2 study testing BMS-986263 in people with Hepatic Cirrhosis and Liver Fibrosis, run by Bristol-Myers Squibb at 1 site in United States.
Trial summary
This is a study of experimental medication BMS-986263 in adult patients with advanced hepatic fibrosis (scar tissue in the liver caused by inflammation that is far on in progress) after the patient is cured of hepatitis C (an infection caused by a virus that attacks the liver and leads to inflammation). Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Hepatic Cirrhosis, Liver Fibrosis
- What is being tested?
- BMS-986263
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2018to 28 May 2019
- 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 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must provide documentation showing a sustained virologic response (SVR) for at least 1 year (52 weeks) prior to the date of screening (SVR is defined as a negative hepatitis C RNA greater than or equal to 12 weeks from the end of therapy)
- Participants must have METAVIR Stage 3 or 4 (or equivalent if using other classification; eg, Ishak)
Who cannot join
- Other causes of liver disease (eg, alcoholic liver disease, HBV [serologically positive as determined using United States Centers for Disease Control and Prevention guidance for interpretation of hepatitis B serologic test results], autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, NASH, hemochromatosis)
- Participants having liver diseases associated with infection with any other hepatitis virus
- Detectable HCV RNA at screening
- Child-Pugh score > 6
- Model for End-Stage Liver Disease score >12
- Evidence of HCC at screening based on alpha-fetoprotein (AFP) levels: AFP > 100 ng/mL (> 82.6 IU/mL) OR AFP ≥ 50 and ≤ 100 ng/mL (≥ 41.3 IU/mL and ≤ 82.6 IU/ mL) with liver ultrasound showing findings suspicious for HCC, or any imaging technique (eg, magnetic resonance imaging [MRI] or computed tomography; based on local assessment), or ultrasound
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- Blood transfusion in the last 6 months prior to screening due to the risk of re-infection with HCV, HBV, HIV, etc
- Participant has any disease or condition which, in the opinion of the investigator, might compromise patient safety (eg, hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, skeletal, central nervous system, or compliment-mediated disease); or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of BMS 986263, or would place the participant at increased risk
- Other protocol defined inclusion/exclusion criteria could apply
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multiple Dose Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986263 in Adults With Advanced Hepatic Fibrosis After Virologic Cure of Hepatitis C
This is a study of experimental medication BMS-986263 in adult patients with advanced hepatic fibrosis (scar tissue in the liver caused by inflammation that is far on in progress) after the patient is cured of hepatitis C (an infection caused by a virus that attacks the liver and leads to inflammation).
- Conditions
- Hepatic Cirrhosis, Liver Fibrosis
- Being tested
- BMS-986263, Placebo
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-986263Drug
Administered by intravenous (IV) infusion
PlaceboOther
Administered by intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1 BMS-986263 45mg weekly | Experimental | Not described Receives: Drug: BMS-986263 |
| Part 1 BMS-986263 90mg weekly | Experimental | Not described Receives: Drug: BMS-986263 |
| Part 1 Placebo weekly | Placebo comparator | Not described Receives: Other: Placebo |
| Part 2 BMS-986263 45mg every 2 weeks | Experimental | Not described Receives: Drug: BMS-986263 |
| Part 2 BMS-986263 90mg every 2 weeks | Experimental | Not described Receives: Drug: BMS-986263 |
| Part 2 BMS-986263 90mg every 4 weeks | Experimental | Not described Receives: Drug: BMS-986263 |
| Part 2 Placebo every 2 weeks | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (METAVIR Score) as Determined by Liver Biopsy After 12 Weeks of Treatment
The number of participants who achieve ≥ 1 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo.
The METAVIR system is used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C virus (HCV). It assesses liver biopsies for activity grade (A0-A3) and fibrosis stage (Stage 1 - 4). Participants without a measurement at Week 12 are considered non-responders.
Activity Grade: A0 = no activity; A1 = mild activity; A2 = moderate activity; A3 = severe activity
Fibrosis stage: 1 = portal fibrosis without septa ; 2 = portal fibrosis with few septa; 3 = numerous septa without cirrhosis; 4 = cirrhosis
Measured: Week 12
Secondary outcomes (6)
Change From Baseline in Collagen Proportionate Area (CPA) After 12 Weeks of Treatment
The change from baseline measurement in Collagen Proportionate Area (CPA) is used to asses the effects of treatment compared to placebo.
Assessment of CPA is a method by which the amount (percentage) of collagen in stained tissue sections is analyzed using morphometric image analysis
Measured: Baseline and Week 12
The Number of Participants With ≥ 1 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment
The number of participants with ≥ 1 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo.
The Ishak scoring system is used to grade fibrosis in the histology samples. The Ishak system (0 through 6 scale) was developed to grade portal-based liver fibrosis associated with viral hepatitis:
0: No fibrosis
- Fibrous expansion of some portal areas, with or without short fibrous septa
- Fibrous expansion of most portal areas, with or without short fibrous septa
- Fibrous expansion of most portal areas with occasional portal to portal bridging
- Fibrous expansion of portal areas with marked bridging (portal to portal as well as portal to central)
- Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis)
- Cirrhosis, probable or definite
Measured: Week 12
The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (METAVIR Score) After 12 Weeks of Treatment
The number of participants with ≥ 2 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo.
The METAVIR system is used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C virus (HCV). It assesses liver biopsies for activity grade (A0-A3) and fibrosis stage (Stage 1 - 4). Participants without a measurement at Week 12 are considered non-responders.
Activity Grade: A0 = no activity; A1 = mild activity; A2 = moderate activity; A3 = severe activity
Fibrosis stage: 1 = portal fibrosis without septa ; 2 = portal fibrosis with few septa; 3 = numerous septa without cirrhosis; 4 = cirrhosis
Measured: Week 12
The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment
The number of participants with ≥ 2 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo.
The Ishak scoring system is used to grade fibrosis in the histology samples. The Ishak system (0 through 6 scale) was developed to grade portal-based liver fibrosis associated with viral hepatitis: 0: No fibrosis
- Fibrous expansion of some portal areas, with or without short fibrous septa
- Fibrous expansion of most portal areas, with or without short fibrous septa
- Fibrous expansion of most portal areas with occasional portal to portal bridging
- Fibrous expansion of portal areas with marked bridging (portal to portal as well as portal to central)
- Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis)
- Cirrhosis, probable or definite
Measured: Week 12
The Number of Participants With ≥ 15% Decrease From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) at Day 85
The number of participants with ≥ 15% decrease from baseline in liver stiffness is used to asses the effects of treatment compared to placebo
Magnetic resonance elastography (MRE) is a noninvasive medical imaging technique that quantitatively measures the stiffness of soft tissues by introducing shear waves and imaging their propagation using magnetic resonance imaging (MRI). MRE will be used to quantitate liver stiffness as a surrogate biomarker of liver fibrosis.
Measured: Baseline and day 85
Change From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) Day 85
Change from baseline in liver stiffness is used to asses the effects of treatment compared to placebo.
Magnetic resonance elastography (MRE) is a noninvasive medical imaging technique that quantitatively measures the stiffness of soft tissues by introducing shear waves and imaging their propagation using magnetic resonance imaging (MRI). MRE will be used to quantitate liver stiffness as a surrogate biomarker of liver fibrosis
Measured: Baseline and day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start14 Feb 2018
- Primary completion10 Dec 2018
- Study completion28 May 2019
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 Hepatic CirrhosisStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe 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
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03420768
- Sponsor's protocol ID
- IM025-006
- Status last verified
- Feb 2022
- First submitted
- 29 Jan 2018
- Last updated
- 4 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Lawitz EJ, Shevell DE, Tirucherai GS, Du S, Chen W, Kavita U, Coste A, Poordad F, Karsdal M, Nielsen M, Goodman Z, Charles ED. BMS-986263 in patients with advanced hepatic fibrosis: 36-week results from a randomized, placebo-controlled phase 2 trial. Hepatology. 2022 Apr;75(4):912-923. doi: 10.1002/hep.32181. Epub 2021 Dec 13.
PubMed 34605045
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multiple Dose Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986263 in Adults With Advanced Hepatic Fibrosis After Virologic Cure of Hepatitis C
- ClinicalTrials.gov ID
- NCT03420768
- Acronym / sponsor ID
- IM025-006
- Conditions
- Hepatic Cirrhosis, Liver Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 14 Feb 2018 (actual)
- Primary completion
- 10 Dec 2018 (actual)
- Study completion
- 28 May 2019 (actual)
- First posted
- 5 Feb 2018 (actual)
- Results
- Posted 4 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study of experimental medication BMS-986263 in adult patients with advanced hepatic fibrosis (scar tissue in the liver caused by inflammation that is far on in progress) after the patient is cured of hepatitis C (an infection caused by a virus that attacks the liver and leads to inflammation).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part 1 BMS-986263 45mg weekly | Experimental | Drug: BMS-986263 |
| Part 1 BMS-986263 90mg weekly | Experimental | Drug: BMS-986263 |
| Part 1 Placebo weekly | Placebo comparator | Other: Placebo |
| Part 2 BMS-986263 45mg every 2 weeks | Experimental | Drug: BMS-986263 |
| Part 2 BMS-986263 90mg every 2 weeks | Experimental | Drug: BMS-986263 |
| Part 2 BMS-986263 90mg every 4 weeks | Experimental | Drug: BMS-986263 |
| Part 2 Placebo every 2 weeks | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Participants must provide documentation showing a sustained virologic response (SVR) for at least 1 year (52 weeks) prior to the date of screening (SVR is defined as a negative hepatitis C RNA greater than or equal to 12 weeks from the end of therapy)
- Participants must have METAVIR Stage 3 or 4 (or equivalent if using other classification; eg, Ishak)
Key exclusion criteria (9 listed)
- Other causes of liver disease (eg, alcoholic liver disease, HBV [serologically positive as determined using United States Centers for Disease Control and Prevention guidance for interpretation of hepatitis B serologic test results], autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, NASH, hemochromatosis)
- Participants having liver diseases associated with infection with any other hepatitis virus
- Detectable HCV RNA at screening
- Child-Pugh score > 6
- Model for End-Stage Liver Disease score >12
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 |
|---|---|---|
| BMS-986263Administered by intravenous (IV) infusion | Drug | Part 1 BMS-986263 45mg weekly, Part 1 BMS-986263 90mg weekly, Part 2 BMS-986263 45mg every 2 weeks, Part 2 BMS-986263 90mg every 2 weeks, Part 2 BMS-986263 90mg every 4 weeks |
| PlaceboAdministered by intravenous (IV) infusion | Other | Part 1 Placebo weekly, Part 2 Placebo every 2 weeks |
Primary outcome
The Number of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (METAVIR Score) as Determined by Liver Biopsy After 12 Weeks of Treatment
Time frame: Week 12
The number of participants who achieve ≥ 1 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo. The METAVIR system is used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C virus (HCV). It assesses liver biopsies for activity grade (A0-A3) and fibrosis stage (Stage 1 - 4). Participants without a measurement at Week 12 are considered non-responders. Activity Grade: A0 = no activity; A1 = mild activity; A2 = moderate activity; A3 = severe activity Fibrosis stage: 1 = portal fibrosis without septa ; 2 = portal fibrosis with few septa; 3 = numerous septa without cirrhosis; 4 = cirrhosis
6 secondary outcomes
Change From Baseline in Collagen Proportionate Area (CPA) After 12 Weeks of Treatment
Time frame: Baseline and Week 12
The Number of Participants With ≥ 1 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment
Time frame: Week 12
The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (METAVIR Score) After 12 Weeks of Treatment
Time frame: Week 12
The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment
Time frame: Week 12
The Number of Participants With ≥ 15% Decrease From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) at Day 85
Time frame: Baseline and day 85
Change From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) Day 85
Time frame: Baseline and day 85
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34605045Lawitz EJ, Shevell DE, Tirucherai GS, Du S, Chen W, Kavita U, Coste A, Poordad F, Karsdal M, Nielsen M, Goodman Z, Charles ED. BMS-986263 in patients with advanced hepatic fibrosis: 36-week results from a randomized, placebo-controlled phase 2 trial. Hepatology. 2022 Apr;75(4):912-923. doi: 10.1002/hep.32181. Epub 2021 Dec 13.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BMS-986263 in people with Hepatic Cirrhosis and Liver Fibrosis, run by Bristol-Myers Squibb at 1 site in United States.
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 2 inclusion and 9 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 4 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 4 Feb 2022). 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?
The Number of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (METAVIR Score) as Determined by Liver Biopsy After 12 Weeks of Treatment (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 NCT03420768, 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 4 Feb 2022.