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出境医 / 临床实验 / A Research Study on How Semaglutide Works in People With Fatty Liver Disease and Liver Damage
A Research Study on How Semaglutide Works in People With Fatty Liver Disease and Liver Damage
Study Description
Brief Summary:
Semaglutide is a medicine studied in patients with non-alcoholic steatohepatitis (NASH), as it may improve liver damage. Participants will either get semaglutide or placebo (a dummy medicine) - which treatment participants get is decided by chance. The study will last for about 61 weeks in total. Participants will have 10 clinic visits and 3 phone calls with the study doctor or staff during the study. Some of the clinic visits may be spread over more days. Participants will need to inject themselves with medicine under the skin. Participants will have to do this once a week for 48 weeks. The study includes magnetic resonance imaging (MRI) scans of the liver, 1 or 2 liver tissue samples, ultrasound scans of the stomach and a possible examination of the food pipe. For some tests participants may need to remove some items of clothing. Participants will stop in the study if the doctor thinks that there are any risks for their health. The information collected from participants during the study may help them and other patients with NASH in the future. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-alcoholic Steatohepatitis | Drug: Semaglutide Drug: Placebo (semaglutide) | Phase 2 |
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 65 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Sponsor staff involved in the clinical trial is masked according to company standard procedures. |
| Primary Purpose: | Treatment |
| Official Title: | Investigation of Efficacy and Safety of Semaglutide s.c. Once-weekly Versus Placebo in Subjects With Non-alcoholic Steatohepatitis and Compensated Liver Cirrhosis |
| Actual Study Start Date : | June 18, 2019 |
| Actual Primary Completion Date : | April 22, 2021 |
| Estimated Study Completion Date : | June 10, 2021 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Semaglutide
Dose escalation to 2.4 mg of semaglutide once-weekly
|
Drug: Semaglutide
Semaglutide given subcutaneously (s.c., under the skin) once-weekly for 48 weeks
|
|
Placebo Comparator: Placebo
Semaglutide placebo once-weekly
|
Drug: Placebo (semaglutide)
Semaglutide placebo s.c. given once-weekly for 48 weeks
|
Outcome Measures
Primary Outcome Measures :
- At least 1 stage of liver fibrosis improvement with no worsening of NASH after 48 weeks (yes/no) (worsening defined as an increase of at least one stage of either lobular inflammation, hepatocyte ballooning or steatosis according to NASH CRN criteria) [ Time Frame: From baseline (week 0) to visit 12 (week 48) ]Yes/no
Secondary Outcome Measures :
- Relative change in liver fat content (percent) measured by magnetic resonance imaging - Proton density fat fraction (MRI-PDFF) [ Time Frame: From baseline (week 0) to visit 12 (week 48) ]Ratio to baseline
- Relative change in liver stiffness measured by MRE [ Time Frame: From baseline (week 0) to visit 12 (week 48) ]Ratio to baseline
- NASH resolution (defined by the NASH CRN as lobular inflammation 0 - 1 and ballooning 0) [ Time Frame: From baseline (week 0) to visit 12 (week 48) ]Yes/no
- Change in stage of fibrosis according to the NASH CRN fibrosis score [ Time Frame: From baseline (week 0) to visit 12 (week 48) ]Scale (0-4) (range of values on absolute scale at one time-point)
- Change in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) according to the NASH CRN criteria [ Time Frame: From baseline (week 0) to visit 12 (week 48) ]Scale (0-8) (range of values on absolute scale at one time-point)
- Number of treatment emergent adverse events [ Time Frame: From baseline (week 0) to visit 12 (week 48) ]Count
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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 above 14 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
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
Contacts and Locations
Locations
| United States, Arizona | |
| Novo Nordisk Investigational Site | |
| Chandler, Arizona, United States, 85224 | |
| Novo Nordisk Investigational Site | |
| Glendale, Arizona, United States, 85306 | |
| United States, California | |
| Novo Nordisk Investigational Site | |
| Coronado, California, United States, 92118 | |
| Novo Nordisk Investigational Site | |
| La Jolla, California, United States, 92037 | |
| Novo Nordisk Investigational Site | |
| Rialto, California, United States, 92377 | |
| United States, Florida | |
| Novo Nordisk Investigational Site | |
| Boca Raton, Florida, United States, 33434 | |
| Novo Nordisk Investigational Site | |
| Gainesville, Florida, United States, 32610 | |
| Novo Nordisk Investigational Site | |
| Miami, Florida, United States, 33136 | |
| United States, Georgia | |
| Novo Nordisk Investigational Site | |
| Atlanta, Georgia, United States, 30309 | |
| Novo Nordisk Investigational Site | |
| Marietta, Georgia, United States, 30060 | |
| United States, Indiana | |
| Novo Nordisk Investigational Site | |
| Indianapolis, Indiana, United States, 46202 | |
| Novo Nordisk Investigational Site | |
| South Bend, Indiana, United States, 46635 | |
| United States, Kentucky | |
| Novo Nordisk Investigational Site | |
| Lexington, Kentucky, United States, 40508 | |
| United States, Maryland | |
| Novo Nordisk Investigational Site | |
| Baltimore, Maryland, United States, 21202 | |
| United States, Massachusetts | |
| Novo Nordisk Investigational Site | |
| Boston, Massachusetts, United States, 02114 | |
| United States, Michigan | |
| Novo Nordisk Investigational Site | |
| Detroit, Michigan, United States, 48202 | |
| United States, North Carolina | |
| Novo Nordisk Investigational Site | |
| Durham, North Carolina, United States, 27710 | |
| United States, Tennessee | |
| Novo Nordisk Investigational Site | |
| Germantown, Tennessee, United States, 38138 | |
| Novo Nordisk Investigational Site | |
| Hermitage, Tennessee, United States, 37076 | |
| Novo Nordisk Investigational Site | |
| Nashville, Tennessee, United States, 37211 | |
| United States, Texas | |
| Novo Nordisk Investigational Site | |
| Arlington, Texas, United States, 76012 | |
| Novo Nordisk Investigational Site | |
| Dallas, Texas, United States, 75390-8887 | |
| Novo Nordisk Investigational Site | |
| San Antonio, Texas, United States, 78215 | |
| United States, Virginia | |
| Novo Nordisk Investigational Site | |
| Richmond, Virginia, United States, 23298 | |
| France | |
| Novo Nordisk Investigational Site | |
| Clichy, France, 92110 | |
| Novo Nordisk Investigational Site | |
| Lyon Cedex 4, France, 69317 | |
| Novo Nordisk Investigational Site | |
| Paris, France, 75014 | |
| Novo Nordisk Investigational Site | |
| Paris, France, 75651 | |
| Novo Nordisk Investigational Site | |
| Venissieux, France, 69200 | |
| Germany | |
| Novo Nordisk Investigational Site | |
| Frankfurt, Germany, 60590 | |
| Novo Nordisk Investigational Site | |
| Leipzig, Germany, 04103 | |
| Novo Nordisk Investigational Site | |
| Mainz, Germany, 55131 | |
| Spain | |
| Novo Nordisk Investigational Site | |
| Barcelona, Spain, 08035 | |
| Novo Nordisk Investigational Site | |
| Sevilla, Spain, 41013 | |
| United Kingdom | |
| Novo Nordisk Investigational Site | |
| Birmingham, United Kingdom, B15 2TH | |
| Novo Nordisk Investigational Site | |
| London, United Kingdom, SE5 9RS | |
| Novo Nordisk Investigational Site | |
| Newcastle upon Tyne, United Kingdom, NE7 7DN | |
| Novo Nordisk Investigational Site | |
| Nottingham, United Kingdom, NG7 2UH | |
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
| Study Director: | Clinical Reporting Anchor and Disclosure (1452) | Novo Nordisk A/S |
| Tracking Information | |||||||
|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | June 12, 2019 | ||||||
| First Posted Date ICMJE | June 17, 2019 | ||||||
| Last Update Posted Date | June 7, 2021 | ||||||
| Actual Study Start Date ICMJE | June 18, 2019 | ||||||
| Actual Primary Completion Date | April 22, 2021 (Final data collection date for primary outcome measure) | ||||||
| Current Primary Outcome Measures ICMJE |
At least 1 stage of liver fibrosis improvement with no worsening of NASH after 48 weeks (yes/no) (worsening defined as an increase of at least one stage of either lobular inflammation, hepatocyte ballooning or steatosis according to NASH CRN criteria) [ Time Frame: From baseline (week 0) to visit 12 (week 48) ] Yes/no
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| Original Primary Outcome Measures ICMJE |
Relative change in liver stiffness measured by magnetic resonance elastography (MRE) [ Time Frame: From baseline (week 0) to visit 12 (week 48) ] Ratio to baseline
|
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| Change History | |||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||
| Descriptive Information | |||||||
| Brief Title ICMJE | A Research Study on How Semaglutide Works in People With Fatty Liver Disease and Liver Damage | ||||||
| Official Title ICMJE | Investigation of Efficacy and Safety of Semaglutide s.c. Once-weekly Versus Placebo in Subjects With Non-alcoholic Steatohepatitis and Compensated Liver Cirrhosis | ||||||
| Brief Summary | Semaglutide is a medicine studied in patients with non-alcoholic steatohepatitis (NASH), as it may improve liver damage. Participants will either get semaglutide or placebo (a dummy medicine) - which treatment participants get is decided by chance. The study will last for about 61 weeks in total. Participants will have 10 clinic visits and 3 phone calls with the study doctor or staff during the study. Some of the clinic visits may be spread over more days. Participants will need to inject themselves with medicine under the skin. Participants will have to do this once a week for 48 weeks. The study includes magnetic resonance imaging (MRI) scans of the liver, 1 or 2 liver tissue samples, ultrasound scans of the stomach and a possible examination of the food pipe. For some tests participants may need to remove some items of clothing. Participants will stop in the study if the doctor thinks that there are any risks for their health. The information collected from participants during the study may help them and other patients with NASH in the future. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period. | ||||||
| Detailed Description | Not Provided | ||||||
| Study Type ICMJE | Interventional | ||||||
| Study Phase ICMJE | Phase 2 | ||||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Masking Description: Sponsor staff involved in the clinical trial is masked according to company standard procedures. Primary Purpose: Treatment
|
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| Condition ICMJE | Non-alcoholic Steatohepatitis | ||||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||
| Recruitment Status ICMJE | Active, not recruiting | ||||||
| Actual Enrollment ICMJE |
65 | ||||||
| Original Estimated Enrollment ICMJE |
69 | ||||||
| Estimated Study Completion Date ICMJE | June 10, 2021 | ||||||
| Actual Primary Completion Date | April 22, 2021 (Final data collection date for primary outcome measure) | ||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
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| Sex/Gender ICMJE |
|
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| Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | ||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
| Listed Location Countries ICMJE | France, Germany, Spain, United Kingdom, United States | ||||||
| Removed Location Countries | |||||||
| Administrative Information | |||||||
| NCT Number ICMJE | NCT03987451 | ||||||
| Other Study ID Numbers ICMJE | NN9931-4492 U1111-1224-4062 ( Other Identifier: World Health Organization (WHO) ) 2018-004484-31 ( Registry Identifier: European Medicines Agency (EudraCT) ) |
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| Has Data Monitoring Committee | No | ||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Novo Nordisk A/S | ||||||
| Study Sponsor ICMJE | Novo Nordisk A/S | ||||||
| Collaborators ICMJE | Not Provided | ||||||
| Investigators ICMJE |
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| PRS Account | Novo Nordisk A/S | ||||||
| Verification Date | June 2021 | ||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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