The effect of semaglutide in people with non-cirrhotic non-alcoholic steatohepatitis (NASH)

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Denmark, European Union, France, Germany, Greece, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Switzerland, T?rkiye, Taiwan, United Kingdom, United States (ICTRP)

ICTRP Studien-ID
EUCTR2019-004594-44 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
The effect of semaglutide in subjects with non-cirrhotic non-alcoholic steatohepatitis (BASEC)

Wissenschaftlicher Titel
The effect of semaglutide in subjects with non-cirrhotic non-alcoholic steatohepatitis - ESSENCE (ICTRP)

Öffentlicher Titel
Research study on whether semaglutide works in people with non-alcoholic steatohepatitis (NASH) (ICTRP)

Untersuchte Krankheit(en)
Non-alcoholic steatohepatitis
MedDRA version: 24.1Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders;Therapeutic area: Diseases [C] - Digestive System Diseases [C06] (ICTRP)

Untersuchte Intervention

Product Name: Semaglutide D 0.5 mg/ml DV3396
Pharmaceutical Form: Solution for injection
INN or Proposed INN: SEMAGLUTIDE
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Semaglutide D 1.0 mg/ml DV3396
Pharmaceutical Form: Solution for injection
INN or Proposed INN: SEMAGLUTIDE
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1.0-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Semaglutide D 2.0 mg/ml DV3396
Pharmaceutical Form: Solution for injection
INN or Proposed INN: SEMAGLUTIDE
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.0-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Semaglutide D 2.27 mg/ml DV3396
Pharmaceutical Form: Solution for injection
INN or Proposed INN: SEMAGLUTIDE
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.27-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Semaglutide D 3.2 mg/mL DV3396
Pharmaceutical Form: Solution for injection
INN or Proposed INN: SEMAGLUTIDE
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concent (ICTRP)

Studientyp
Interventional clinical trial of medicinal product (ICTRP)

Studiendesign
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2 (ICTRP)

Ein-/Ausschlusskriterien
Gender:
Female: yes
Male: yes

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
the 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 steatosis, lobular inflammation and
hepatocyte ballooning based on a central pathologist evaluation of the baseline liver biopsy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 960
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 240
(ICTRP)

Exclusion criteria:
? Documented causes of chronic liver disease other than non-alcoholic fatty liver disease
(NAFLD)
? Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V2A) or any known
presence of HCV RNA or HBsAg within 2 years of screening (V2A).
? Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at randomisation.
? Known or suspected excessive consumption of alcohol (greater than 20 g/day for women or greater than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)).
? Treatment with vitamin E (at doses greater than or equal to 800 IU/day) or pioglitazone or medications approved for treatment of NASH which has not been at a stable dose 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 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 (V2A).
? 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.


Primäre und sekundäre Endpunkte
Main Objective: 1. Part 1: To demonstrate that treatment with semaglutide 2.4 mg administered subcutaneously (under the skin, s.c.) improves liver histology compared to placebo in subjects with NASH and fibrosis stage 2 or 3.
2. Part 2: To demonstrate that treatment with semaglutide s.c. 2.4 mg lowers the risk of liver-related clinical events compared to placebo in subjects with NASH and fibrosis stage 2 or 3.;Secondary Objective: 1. To demonstrate that treatment with semaglutide s.c. 2.4 mg lowers body weight compared to placebo in subjects with NASH and fibrosis stages 2 or 3.
2. 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.
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.
4. To compare the effect of semaglutide s.c. 2.4 mg versus placebo on biomarkers related to fibrosis in subjects with NASH and fibrosis stages 2 or 3.;Primary end point(s): Part 1:
1. Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No)
2. Improvement in liver fibrosis and no worsening of steatohepatitis (Yes/No)

Part 2:
3. Cirrhosis-free survival (Yes/No);Timepoint(s) of evaluation of this end point: 1.- 2. From randomisation (week 0) to week 72
3. From randomisation (week 0) to week 240 (ICTRP)

Secondary end point(s): 1. Change in body weight
2. Resolution of steatohepatitis and improvement in liver fibrosis
(Yes/No)
3. Change in Short Form 36 v2.0 acute (SF-36) Bodily Pain
4. Change in body weight
5. Improvement in steatohepatitis with at least a 2-point reduction in
NAS and no worsening of fibrosis (Yes/No)
6. Change in histology-assessed liver collagen proportionate area
7. Worsening in steatohepatitis (Yes/No)
8. Improvement in histology-assessed ballooning (Yes/No)
9. Improvement in histology-assessed inflammation (Yes/No)
10. Improvement in histology-assessed steatosis (Yes/No)
11. NASH resolution (ballooning of 0, inflammation of 0-1) and =2point
NAS reduction with no worsening of fibrosis
12. Progression of liver fibrosis in patients with F2 at baseline (Yes/No)
13. Progression of liver fibrosis
14. Resolution of steatohepatitis and no worsening of liver fibrosis
(Yes/No)
15. Improvement in liver fibrosis and no worsening of steatohepatitis
(Yes/No)
16. Changes in liver stiffness values assessed by transient elastography
(FibroScan?f)
17. Change in ELF score
18. Change in alanine aminotransferase (ALT)
19. Change in aspartate aminotransferase (AST)
20. Change in CAP values assessed by transient elastography
(FibroScan)
21. Change in FAST score
22. Change in Pro-C3
23. Change in inflammation assessed by hsCRP
24. Change in HbA1c
25. Change in triglyceride
26. Change in free fatty acids
27. Change in LDL cholesterol
28. Change in HDL cholesterol
29. Time to first Major Adverse Cardiovascular Event (MACE) (composite
endpoint)
30. Major cardio-hepatic event-free survival (Yes/No)
31. Changes in SF-36 Physical Component Summary
32. Changes in SF-36 Mental Component Summary
33. Change in SF-36 Bodily Pain
34. Changes in NASH-CHECK Abdominal Pain;Timepoint(s) of evaluation of this end point: 1. - 3. From randomisation (week 0) to week 72
4. From randomisation (week 0) to week 240
5. - 13. From randomisation (week 0) to week 72
14. - 15. From randomisation (week 0) to week 240
16.- 17. From randomisation (week 0) to week 72
18. - 28. From randomisation (week 0) to week 72 and week 240
29. - 30. From randomisation (week 0) to week 240
31. - 32.. From randomisation (week 0) to week 72 and week 240
33. From randomisation (week 0) to week 240
34. From randomisation (week 0) to week 72 and week 240 (ICTRP)

Registrierungsdatum
23.02.2021 (ICTRP)

Einschluss des ersten Teilnehmers
17.02.2021 (ICTRP)

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Clinical Transparency (2834), clinicaltrials@novonordisk.com, Novo Nordisk A/S (ICTRP)

Sekundäre IDs
NN9931-4553, 2019-004594-44-NO (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004594-44 (ICTRP)