E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Compensated Cirrhosis from Nonalcoholic Steatohepatitis (NASH) |
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E.1.1.1 | Medical condition in easily understood language |
Compensated Cirrhosis from Nonalcoholic Steatohepatitis (NASH) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10019669 |
E.1.2 | Term | Hepatic fibrosis and cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064844 |
E.1.2 | Term | Compensated cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
_To evaluate the efficacy of BMS-986263 compared with placebo to improve liver fibrosis in participants with compensated cirrhosis due to NASH |
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E.2.2 | Secondary objectives of the trial |
_To further assess the efficacy of BMS-986263 compared with placebo to improve liver fibrosis, as determined by liver biopsy, in participants with compensated cirrhosis due to NASH; _To assess the safety and tolerability of BMS-986263 in participants with compensated cirrhosis due to NASH; _To assess the PK of BMS-986263 in participants with compensated cirrhosis due to NASH |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
_13C MBT Substudy v1.0, dd 19-Nov-2019 (will not be pursued at this time at any of the participating sites) OBJECTIVES: To assess the effect of treatment with BMS-986263 on liver function
_HepQuant- SHUNT Test Substudy (only US sites are participating to this substudy, no further details will be mentioned in this form and no supporting documentation will be provided) OBJECTIVES: To assess the effect of treatment with BMS-986263 on liver function
_MRE Substudy (at Sites Where Available) OBJECTIVES: To evaluate the efficacy of BMS-986263 compared with placebo in regards to liver stiffness. |
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E.3 | Principal inclusion criteria |
-Participants with liver biopsy fibrosis score stage 4 performed within 6 months -Men and women must agree to follow methods of contraception |
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E.4 | Principal exclusion criteria |
-Worsening liver disease or any disease might compromise participant safety in the opinion of the investigator; -Known immunocompromised status or any disease or condition which might compromise participant safety; -Prior exposure to BMS-986263 -Clinically relevant abnormal physical examination, vital signs, ECG, or clinical laboratory tests; -Hepatic decompensation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
_Proportion of participants who achieve ≥ 1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score), as determined by liver biopsy after 12 weeks of treatment;
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
_after 12 weeks of treatment |
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E.5.2 | Secondary end point(s) |
_Proportion of participants with ≥1 stage improvement in liver fibrosis with no increase of the NAS [NAFLD (Nonalcoholic fatty liver disease) Activity Score] by ≥ 1 point after 12 weeks of treatment ;_Proportion of participants with ≥2 stage improvement in liver fibrosis score (NASH CRN Fibrosis Score) after 12 weeks of treatment; _Proportion of participants with ≥ 1 stage improvement in modified Ishak liver fibrosis score after 12 weeks of treatment; _Proportion of participants with ≥ 2 stage improvement in modified Ishak liver fibrosis score after 12 weeks of treatment; _Change from baseline in collagen proportionate area (CPA) after 12 weeks of treatment; _Incidences of SAEs, AEs, clinical laboratory values, vital signs, physical examination findings, and ECGs up to week 36 _Change from baseline in bone mineral density (BMD), as measured by dual-energy x-ray absorptiometry (DXA), at week 36 _Plasma concentrations of BMS-986263 day 1 to week 12; _Plasma concentrations of DPD (di-retinamide-PEG-diretinamide), day 1 to week 12; _Plasma concentrations of S104 (lipid component), day 1 to week 12. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
day 1, after 12 weeks of treatment, at Follow-up Week 24 or throughout the study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Canada |
Israel |
Japan |
Korea, Republic of |
Puerto Rico |
Taiwan |
United States |
France |
Spain |
Switzerland |
Germany |
Italy |
Belgium |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study (EOS) is defined as the last visit or scheduled procedure shown in the Schedule of Activities (Section 1.3 from the protocol) for the last participant. Study completion is defined as the final date on which data for the primary endpoint was or is expected to be collected, if this is not the same. The end of the study for analysis of biomarker samples is included in Section 8.6. of the protocol. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |