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Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH)

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ClinicalTrials.gov Identifier: NCT05016882
Recruitment Status : Recruiting
First Posted : August 23, 2021
Last Update Posted : January 10, 2022
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Tracking Information
First Submitted Date  ICMJE August 18, 2021
First Posted Date  ICMJE August 23, 2021
Last Update Posted Date January 10, 2022
Actual Study Start Date  ICMJE August 31, 2021
Estimated Primary Completion Date May 8, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2021)
Improvement in liver fibrosis and no worsening of NASH (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
Count of subjects Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2021)
  • Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
    Count of subjects Resolution of steatohepatitis is defined as a NAS of 0-1 for inflammation, 0 for ballooning and any value for steatosis according to NASH CRN52. Fibrosis is graded on the NASH CRN (Non-Alcoholic Steatohepatitis Clinical Research Network) fibrosis scale from 0 to 4.
  • Improvement in steatohepatitis with at least a 2-point reduction in NAS and no worsening of fibrosis (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
    Count of subjects The 2-point reduction must include at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning.
  • Change in histology-assessed liver collagen proportionate area [ Time Frame: From baseline (week 0) to week 52 ]
    Ratio to baseline
  • Resolution of steatohepatitis and improvement in liver fibrosis (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
    Count of subjects Resolution of steatohepatitis is defined as an NAS score of 0-1 for inflammation, 0 for ballooning and any value for steatosis (according to NASH CRN). Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale
  • Improvement in liver fibrosis (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
    Count of subjects Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale
  • Progression of liver fibrosis (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
    Count of subjects For subjects with fibrosis stage 2 or 3 at baseline
  • Worsening in steatohepatitis (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
    Count of subjects Worsening in steatohepatitis is defined as increase in NAS score for ballooning, inflammation or steatosis
  • Improvement in ballooning (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
    Count of subjects
  • Improvement in inflammation (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
    Count of subjects
  • Improvement in steatosis (Yes/No) [ Time Frame: From baseline (week 0) to week 52 ]
    Count of subjects
  • Change in ALT (alanine aminotransferase) [ Time Frame: From baseline (week 0) to week 52 ]
    Ratio to baseline
  • Change in AST (aspartate aminotransferase) [ Time Frame: From baseline (week 0) to week 52 ]
    Ratio to baseline
  • Change in inflammation assessed by HsCRP (high sensitivity C-reactive protein) [ Time Frame: From baseline (week 0) to week 52 ]
    Ratio to baseline
  • Change in ELF (Enhanced Liver Fibrosis) score [ Time Frame: From baseline (week 0) to week 52 ]
    Logarithm
  • Change in HbA1c. For subjects with type 2 diabetes [ Time Frame: From baseline (week 0) to week 52 ]
    %-points (absolute change)
  • Change in triglycerides [ Time Frame: From baseline (week 0) to week 52 ]
    Ratio to baseline
  • Change in free fatty acids [ Time Frame: From baseline (week 0) to week 52 ]
    Ratio to baseline
  • Change in LDL (low density lipoprotein) cholesterol [ Time Frame: From baseline (week 0) to week 52 ]
    Ratio to baseline
  • Change in HDL (high density lipoprotein) cholesterol [ Time Frame: From baseline (week 0) to week 52 ]
    Ratio to baseline
  • Relative change in body weight [ Time Frame: From baseline (week 0) to week 52 ]
    Percentage
  • Change in SF-36 (36-item Short Form Survey) bodily pain [ Time Frame: From baseline (week 0) to week 52 ]
    Points
  • Change in NASH-CHECK (patient-reported outcome measure for non-alcoholic steatohepatitis)pain [ Time Frame: From baseline (week 0) to week 52 ]
    Points
  • Change in PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue score [ Time Frame: From baseline (week 0) to week 52 ]
    Points
  • Number of treatment emergent adverse events (TEAEs) [ Time Frame: From baseline (week 0) to week 59 ]
    Count
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH)
Official Title  ICMJE Efficacy and Safety Investigation of NNC0194-0499 Co-administered With Semaglutide in Subjects With Non-alcoholic Steatohepatitis: a Dose-ranging, Placebo Controlled Trial
Brief Summary

This study is being done to see if a combination of 2 medicines (called NNC0194-0499 and semaglutide) can reduce liver damage in patients with non alcoholic steatohepatitis (NASH).

NNC0194-0499 is a new medicine which works in the liver. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries. It also helps with weight loss and may reduce liver damage, and so prevent future liver complications. It works in a different way to NNC0194 0499. The 2 medicines may work better together than on their own.

The study will also look at a combination of semaglutide and another weight-loss medicine called NNC0174-0833, which may be another treatment option for NASH.

Each week, participants will get 2 injections. These could be 2 of the 3 medicines OR 1 of the medicines and a placebo OR 2 placebo injections. Which treatment participants get is decided by chance. A placebo is a dummy medicine which looks like the real medicine but doesn't contain any active medicine.

The study will last for about 19 months. Participants will have 14 clinic visits and 9 phone calls with the study doctor.

Participants will have 1 or 2 liver biopsies (tiny pieces of liver tissue) - one at the start (if participants have not had a biopsy recently) and one at the end of the study treatment.

Women: 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
Intervention Model Description:
This is a randomised, double-blind, active and placebo-controlled, double-dummy, parallel group, multinational trial investigating NNC0194-0499 at 3 different dose levels when co administered with semaglutide
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non-alcoholic Steatohepatitis
Intervention  ICMJE
  • Drug: NNC0194 0499 50 mg/mL
    Patients will receive subcutaneous (s.c., under the skin) injections of NNC0194-0499 once weekly The study will last for about 19 months
  • Drug: Placebo (NNC0194-0499)
    Patients will receive subcutaneous (s.c., under the skin) injections of placebo once weekly The study will last for about 19 months
  • Drug: Semaglutide 3 mg/mL
    Patients will receive subcutaneous (s.c., under the skin) injections of semaglutide once weekly The study will last for about 19 months
  • Drug: Semaglutide placebo
    Patients will receive subcutaneous (s.c., under the skin) injections of semaglutide placebo once weekly The study will last for about 19 months
  • Drug: NNC0174 0833 10 mg/mL
    Patients will receive subcutaneous (s.c., under the skin) injections of NNC0174-0833 once weekly The study will last for about 19 months
  • Drug: NNC0174 0833 placebo
    Patients will receive subcutaneous (s.c., under the skin) injections of NNC0174-0833 placebo once weekly The study will last for about 19 months
Study Arms  ICMJE
  • Experimental: NNC0194-0499 7.5 mg + semaglutide 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Interventions:
    • Drug: NNC0194 0499 50 mg/mL
    • Drug: Semaglutide 3 mg/mL
  • Placebo Comparator: Placebo (NNC0194-0499) 7.5 mg + semaglutide placebo 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Interventions:
    • Drug: Placebo (NNC0194-0499)
    • Drug: Semaglutide placebo
  • Experimental: NNC0194-0499 15 mg + semaglutide 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Interventions:
    • Drug: NNC0194 0499 50 mg/mL
    • Drug: Semaglutide 3 mg/mL
  • Placebo Comparator: Placebo (NNC0194-0499) 15 mg + semaglutide placebo 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Interventions:
    • Drug: Placebo (NNC0194-0499)
    • Drug: Semaglutide placebo
  • Experimental: NNC0194-0499 30 mg + semaglutide 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Intervention: Drug: NNC0194 0499 50 mg/mL
  • Experimental: NNC0194-0499 30 mg + semaglutide placebo 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Interventions:
    • Drug: NNC0194 0499 50 mg/mL
    • Drug: Semaglutide placebo
  • Active Comparator: Placebo (NNC0194-0499) 30 mg + semaglutide 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Interventions:
    • Drug: Placebo (NNC0194-0499)
    • Drug: Semaglutide 3 mg/mL
  • Placebo Comparator: Placebo (NNC0194-0499) 30 mg + semaglutide placebo 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Interventions:
    • Drug: Placebo (NNC0194-0499)
    • Drug: Semaglutide placebo
  • Experimental: NNC0174-0833 2.4 mg + semaglutide 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Interventions:
    • Drug: Semaglutide 3 mg/mL
    • Drug: NNC0174 0833 10 mg/mL
  • Placebo Comparator: Placebo (NNC0174-0833) 2.4 mg + semaglutide placebo 2.4 mg
    Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
    Interventions:
    • Drug: Semaglutide placebo
    • Drug: NNC0174 0833 placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 18, 2021)
672
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 20, 2024
Estimated Primary Completion Date May 8, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged greater than or equal to 18 years at the time of signing informed consent. In Republic of Korea, subjects must be aged greater than or equal to 19 years. In Japan, subjects must be aged greater than or equal to 20 years. In Singapore, subjects must be aged greater than or equal to 21 years.
  • 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 Visit 1.
  • Histological evidence of fibrosis stage 2, 3 or 4 according to the NASH CRN classification based on a central pathologist evaluation of the baseline liver biopsy.
  • Histological non-alcoholic fatty liver disease (NAFLD) activity score (NAS) greater than or equal to 4 for subjects with F2/F3 or greater than or equal to 3 for subjects with F4 based on a central pathologist evaluation of the baseline liver biopsy. All subjects must have a score of 1 or more in steatosis, lobular inflammation and hepatocyte ballooning.

Exclusion Criteria:

  • Documented causes of chronic liver disease other than 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 more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at V2A.
  • For subjects with F4, presence or history of gastro-oesophageal varices more than or equal to grade 2 at V3. An oesophagogastroduodenoscopy performed no more than 52 weeks prior to V3 must be available at V3.
  • Known or suspected excessive consumption of alcohol (more than 20 g/day for women or more 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 more than or equal to 800 IU/day) or pioglitazone or medications approved for the 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 V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A.
  • Treatment with GLP-1 RAs within 90 days prior to V2A. Subjects with a historical liver biopsy taken more than 90 days prior to V2A are excluded if they receive treatment with GLP-1 RAs from time of biopsy until 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 V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novo Nordisk (+1) 866-867-7178 clinicaltrials@novonordisk.com
Listed Location Countries  ICMJE Australia,   Belgium,   Bulgaria,   Canada,   France,   Germany,   Greece,   India,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Poland,   Puerto Rico,   Russian Federation,   Singapore,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05016882
Other Study ID Numbers  ICMJE NN9500-4656
U1111-1255-5551 ( Other Identifier: World Health Organization (WHO) )
2020-003566-39 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: http://novonordisk-trials.com
Responsible Party Novo Nordisk A/S
Study Sponsor  ICMJE Novo Nordisk A/S
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Transparency (dept. 1452) Novo Nordisk A/S
PRS Account Novo Nordisk A/S
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP