This study has been transitioned to CTIS with ID 2023-506962-30-00 check the CTIS register for the current data. Primary objectivesThe trial has two parts, a part 1 and a part 2, with distinctive objectives and endpoints.Part 1 of the trial: To…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint
Part 1 (two separate endpoints):
Resolution of steatohepatitis and no worsening of liver fibrosis - From
randomisation (week 0) to week 72
Improvement in liver fibrosis and no worsening of steatohepatitis - From
randomisation (week 0) to week 72
Part 2:
Time to first liver-related clinical event (composite endpoint) - From
randomisation (week 0) to week 240
Secondary outcome
Secondary confirmatory endpoint
Progression of liver fibrosis - From randomisation (week 0) to week 72
Change in body weight - From randomisation (week 0) to week 72
Change in SF-36 Bodily Pain - From randomisation (week 0) to week 72
Change in body weight - From randomisation (week 0) to week 240
Background summary
Non-alcoholic steatohepatitis (NASH) is associated with increased risk of
morbidity and mortality. Currently, treatment options are few and insufficient.
There is therefore an unmet medical need for effective and safe pharmacological
treatments options. Semaglutide, a glucagon-like peptide-1 receptor agonist
(GLP-1 RA), has the potential to address metabolic and histological aspects of
NASH and is therefore considered a strong candidate for the treatment of NASH.
Study objective
This study has been transitioned to CTIS with ID 2023-506962-30-00 check the CTIS register for the current data.
Primary objectives
The trial has two parts, a part 1 and a part 2, with distinctive objectives and
endpoints.
Part 1 of the trial: To demonstrate that treatment with semaglutide s.c.
improves liver histology compared to placebo in subjects with NASH and fibrosis
stage 2 or 3.
Part 2 of the trial: To demonstrate that treatment with semaglutide s.c. lowers
the risk of liverrelated clinical events compared to placebo in subjects with
NASH and fibrosis stage 2 or 3.
Secondary objectives
To demonstrate that treatment with semaglutide s.c. lowers body weight compared
to placebo in subjects with NASH and fibrosis stages 2 or 3.
To demonstrate that treatment with semaglutide s.c. 2.4 mg improves
patient-reported outcomes compared to placebo in subjects with NASH and
fibrosis stages 2 or 3.
To compare the effects of semaglutide s.c. 2.4 mg versus placebo on
cardiovascular disease and cardio-metabolic factors in subjects with NASH and
fibrosis stages 2 or 3
To compare the effect of semaglutide s.c. versus placebo on biomarkers related
to fibrosis in subjects with NASH and fibrosis stages 2 or 3.
Study design
This is a randomised, multicentre, double-blinded, parallel-group trial
comparing semaglutide s.c. once-weekly versus placebo in subjects with NASH and
fibrosis stage 2 or 3.
The total trial duration for each subject is approximately 257 weeks (~4 years
and 11 months). This includes a screening period of approximately 10 weeks
followed by randomisation and a 240-week treatment period. The follow-up period
is 7 weeks.
Subjects will be randomised 2:1 to receive treatment with semaglutide s.c. or
placebo. The randomisation will be stratified based on the presence of type 2
diabetes (T2D) at screening, fibrosis stage and region. For both semaglutide
s.c. and placebo there will be a period of dose escalation
before reaching the target dose administrated subcutaneously once-weekly. All
subjects must aim at reaching the recommended target dose of semaglutide.
Intervention
Once weekly subcutaneous semaglutide injection 2.4mg.
Study burden and risks
Necessary precautions have been implemented in the design and planned conduct
of the trial to minimise the risks and inconveniences of participation. The
safety profile for semaglutide has not revealed any safety issue that would
prohibit administration of semaglutide in patients with NASH. On the contrary,
previous studies suggest that semaglutide could provide clinically meaningful
treatment effects for patients with NASH. Assessment of NASH and appropriate
attention to the standard-of care treatment will be provided throughout the
trial. Therefore, although there is a small risk associated with performing a
liver biopsy, it is concluded that the potential benefits of trial
participation will outweigh the potential risks for both semaglutide- and
placebo-treated subjects.
Flemingweg 8
Alphen aan den Rijn 2408AV
NL
Flemingweg 8
Alphen aan den Rijn 2408AV
NL
Listed location countries
Age
Inclusion criteria
- Age above or equal to 18 years at the time of signing informed consent.
- Histological evidence of NASH based on a central pathologist evaluation of
the baseline liver biopsy. The baseline liver biopsy can be a historical biopsy
obtained within 180 days prior to screening visit (V1).
- Histological evidence of fibrosis stage 2 or stage 3 according to the NASH
CRN classification based on a central pathologist evaluation of the baseline
liver biopsy.
- A histological NAS >= 4 with a score of 1 or more in both steatosis, lobular
inflammation and hepatocyte ballooning based on a central pathologist
evaluation of the baseline liver biopsy.
Exclusion criteria
- Positive HBsAg, positive anti-HIV, positive HCV-RNA at screening or any known
presence of HCV RNA or HBsAg within 2 years of screening (V2A).
- Documented causes of chronic liver disease other than Non-Alcoholic Fatty
Liver Disease NAFLD.
- Presence or history of ascites, variceal bleeding, hepatic encephalopathy,
spontaneous bacterial peritonitis or liver transplantation at randomisation.
- Known or suspected excessive consumption of alcohol (>20 g/day for women or
>30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders
Identification Test (AUDIT questionnaire).
- Treatment with vitamin E (at doses >=800 IU/day) or pioglitazone or
medications approved for treatment of NASH which has not been at a stable dose
in the opinion of the investigator in the period from 90 days prior to the
screening visit (V2A). In addition, for subjects with historical liver biopsies
taken more than 90 days prior to screening, treatment should be at a stable
dose in the opinion of the investigator from time of biopsy until screening.
- Treatment with GLP-1 RAs in the period from 90 days prior to the screening
visit (V2A). In addition, for subjects with historical liver biopsies taken
more than 90 days prior to screening, any treatment with GLP-1 RAs from time of
biopsy until screening.
- Treatment with glucose lowering agent(s) (other than GLP-1 RAs), lipid
lowering medication or weight loss medication not stable in the opinion of the
investigator in the period from 90 days prior to the screening visit (V2A). In
addition, for subjects with historical liver biopsies taken more than 90 days
prior to screening, treatment should be at a stable dose in the opinion of the
investigator from time of biopsy until screening.
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506962-30-00 |
| EudraCT | EUCTR2019-004594-44-NL |
| CCMO | NL75689.018.20 |