E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-alcoholic steatohepatitis
Compensated liver cirrhosis |
|
E.1.1.1 | Medical condition in easily understood language |
Non-alcoholic steatohepatitis (NASH)
Compensated liver cirrhosis |
|
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 | 20.1 |
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 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024667 |
E.1.2 | Term | Liver cirrhosis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
|
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 investigate the effect of semaglutide subcutaneous (s.c.) 2.4 mg once-weekly on liver fibrosis compared with placebo in subjects with NASH and compensated fibrosis stage 4 |
|
E.2.2 | Secondary objectives of the trial |
1. To investigate the effect of semaglutide s.c. 2.4 mg once-weekly on NASH compared with placebo in subjects with NASH and compensated fibrosis stage 4
2, To evaluate the safety and tolerability of semaglutide s.c. 2.4 mg once-weekly compared with placebo in subjects with NASH and compensated fibrosis stage 4 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent.
- Histologic evidence of NASH and fibrosis stage 4 according to the NASH CRN classification based on central pathologist evaluation of a liver biopsy obtained within 360 days prior to screening. In subjects who have never had a liver biopsy showing NASH and F4, liver stiffness above14 kPa by FibroScan® at screening must be documented before subjects can have a trial-related liver biopsy
- A histological NAFLD activity score (NAS) equal to or above 3 with a score of 1 or more in lobular inflammation and hepatocyte ballooning based on central pathologist evaluation
- Body mass index equal to or above 27 kg/m^2 |
|
E.4 | Principal exclusion criteria |
- Presence or history of hepatic decompensation (e.g. ascites, variceal bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis) or liver transplantation
- Presence or history of gastroesophageal varices within the past 360 days prior to screening. For subjects with no known history of gastroesophageal varices and with a Fibroscan® equal to or above 20 kPa and thrombocytes equal to or below 150,000, a esophagogastroduodenoscopy must be performed to evaluate presence of gastroesophageal varices
- Presence or history of hepatocellular carcinoma
- Treatment with vitamin E (at doses equal to or above 800 IU/day) or pioglitazone which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to screening
- Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the period from 90 days prior to screening
- Treatment with other glucose lowering agent(s) (apart from what is listed in the exclusion criterion above) or weight loss medication not stable in the opinion of the investigator in the period from 28 days prior to screening |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Relative change in liver stiffness measured by MRE |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline (week 0) to visit 12 (week 48) |
|
E.5.2 | Secondary end point(s) |
1. Relative change in liver fat content (%) measured by MRI-PDFF
2. At least one stage of liver fibrosis improvement with no worsening of NASH (yes/no) (worsening defined as an increase of at least one stage of either lobular inflammation, hepatocyte ballooning or steatosis according to the NASH CRN criteria)
3. NASH resolution (yes/no) (defined by the NASH CRN as lobular inflammation 0 – 1 and ballooning 0)
4. Change in Stage of fibrosis according to the NASH CRN fibrosis score
5. Change in NAFLD activity score (NAS) according to the NASH CRN criteria
6. Number of treatment emergent adverse events |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints:
From baseline (week 0) to visit 12 (week 48) |
|
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 | No |
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 |
|
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 | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
European Union |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
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 | 29 |