E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-alcoholic steatohepatitis (NASH) |
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E.1.1.1 | Medical condition in easily understood language |
NASH is liver inflammation and damage caused by a buildup of fat in the liver in patients who are not alcoholic |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053219 |
E.1.2 | Term | Non-alcoholic steatohepatitis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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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 BFKB8488A compared with placebo on the basis of resolution of NASH without worsening of fibrosis |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of BFKB8488A compared with placebo on the basis of hepatic fat fraction assessed by magnetic resonance imaging- derived proton density fat fraction (MRI-PDFF), proportion of patients with improvement in liver histology in non-alcoholic fatty liver disease (NAFLD) activity score [NAS], in liver fibrosis greater than or equal to one stage and no worsening of steatohepatitis
• To evaluate the safety of BFKB8488A compared with placebo on the basis of incidence and severity of adverse events, changes in vital signs, clinical laboratory test results
• To evaluate the BFKB8488A pharmacokinetic (PK) profile on the basis of the serum concentration of BFKB8488A
• To evaluate the immune response to BFKB8488A on the basis of incidence and titer of anti-drug antibodies (ADAs)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 and <= 75 years
- Hepatic steatosis on MRI (>= 8% average liver PDFF) prior to randomization
- Confirmed diagnosis of NASH as documented through liver biopsy performed no more than 6 months before randomization, defined according to NASH CRN criteria along with a NASH CRN fibrosis score between F2 and F3
- Use of highly effective contraception as defined by the protocol
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E.4 | Principal exclusion criteria |
- Patients with Type 1 diabetes, or on treatment with glucagon-like peptide-1 receptor agonists and/or thiazolidinediones
- Treatment with drugs historically associated with NAFLD for more than 2 weeks within the year prior to randomization
- History of endocrine diseases defined in the protocol including but not limited to Cushing’s disease, Addison’s disease, and hyper- or hypo-thyroidism
- History of any liver disease other than NASH, except for resolved, self-limited illnesses such as hepatitis A or E, and previous Hepatitis C and liver transplantation
- Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2
- Evidence of functional hepatic impairment, other forms of chronic liver disease, and cholelithiasis on ultrasound at screening - Liver enzymes levels >= 5 × upper limit of normal (ULN), Alkaline phosphatase >= 2 × ULN and total bilirubin > ULN at screening
- Actively involved in a structured weight loss, dietary program, treatment with medications for the purpose of weight loss, or planned medical procedure or surgery during the study
- Weight gain or loss > 5% within 3 months prior to randomization
- Patients with osteoporosis, other bone diseases/conditions, or have a history or are current on bone active treatments prohibited by the protocol
- Current or history of significant alcohol consumption
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Proportion of patients with resolution of NASH on overall histopathological reading, without worsening of fibrosis at Week 52 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Change from baseline in hepatic fat fraction as assessed by MRI-PDFF at Week 52
2.Proportion of patients improvement in fibrosis of at least 1 stage from baseline with no worsening of NASH at Week 52
3.Proportion of patients improvement in NAS score by at least 2 points from baseline at Week 52
4.Incidence and severity of adverse events, with severity determined according to the
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
5.Change from baseline in targeted vital signs
6.Change from baseline in targeted clinical laboratory test results
7.Maximum serum concentration observed (Cmax) of BFKB8488A
8.Minimum serum concentration observed (Cmin) of BFKB8488A
9.Incidence and titer of ADAs during the study relative to the prevalence of ADAs at baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At Week 52
2-3. At Week 52
4. Up to Week 58 (or up to 6 weeks after the final dose of study drug)
5-6. Baseline to Week 58
7-8. Week 0, Week 4, Week 8, Week 12, Week 16, Week 28, Week 29, Week 40, Week 52, Week 58 and unscheduled visit
9. Week 0, Week 4, Week 8, Week 12, Week 16, Week 28, Week 40, Week 52, Week 58 and unscheduled visit
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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 |
Biomarkers, Immunogenicity, Quality of life |
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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 | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Belgium |
France |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |