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A Study to Evaluate the Safety and Efficacy of Cotadutide Given by Subcutaneous Injection in Adult Participants With Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis. (PROXYMO-ADV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05364931
Recruitment Status : Active, not recruiting
First Posted : May 6, 2022
Last Update Posted : May 3, 2023
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:
The purpose of this study is to evaluate the safety and efficacy of cotadutide in participants with non-cirrhotic NASH with fibrosis.

Condition or disease Intervention/treatment Phase
Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis Drug: Cotadutide Drug: Placebo Phase 2 Phase 3

Detailed Description:
A Phase 2b/3, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of two different doses of cotadutide at 300 and 600 μg in participants with non-cirrhotic non-alcoholic steatohepatitis with fibrosis.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIb/III Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Cotadutide in Participants With Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis
Actual Study Start Date : July 14, 2022
Estimated Primary Completion Date : April 24, 2024
Estimated Study Completion Date : April 24, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cotadutide 300μg Drug: Cotadutide
Cotadutide administered subcutaneously once daily
Placebo Comparator: Placebo 300μg Drug: Placebo
Placebo administered subcutaneously once daily
Experimental: Cotadutide 600μg Drug: Cotadutide
Cotadutide administered subcutaneously once daily
Placebo Comparator: Placebo 600μg Drug: Placebo
Placebo administered subcutaneously once daily


Outcome Measures
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Primary Outcome Measures :
  1. Part A: Proportion of participants with resolution of NASH without worsening of liver fibrosis based on biopsy [ Time Frame: Week 48 ]
    To determine whether cotadutide is superior to placebo on resolution of NASH without worsening of liver fibrosis in participants with non-cirrhotic NASH with fibrosis

  2. Part B: Proportion of participants with resolution of NASH without worsening of liver fibrosis based on biopsy [ Time Frame: Week 84 ]
    To determine whether cotadutide is superior to placebo on resolution of NASH without worsening of liver fibrosis

  3. Part B: Proportion of participants with improvement of liver fibrosis by at least one stage without worsening of NASH based on biopsy [ Time Frame: Week 84 ]
    To determine whether cotadutide is superior to placebo on improvement of liver fibrosis by at least one stage without worsening of NASH


Secondary Outcome Measures :
  1. Part A: Proportion of participants with improvement of liver fibrosis by at least one stage without worsening of NASH [ Time Frame: Week 48 ]
    To assess the effect of cotadutide versus placebo on improvement in fibrosis by at least one stage without worsening of NASH

  2. Part A: Proportion of participants with ≥ 2-point improvement from baseline in NAS based on biopsy [ Time Frame: Week 48 ]
    To assess the effect of cotadutide versus placebo on ≥ 2-point improvement in NAS

  3. Part A: Proportion of participants with both resolution of NASH and improvement in fibrosis by at least one stage [ Time Frame: Week 48 ]
    To assess the effect of cotadutide versus placebo on resolution of NASH and improvement in fibrosis

  4. Part A: Proportion of participants with improvement in fibrosis by at least one stage based on biopsy [ Time Frame: Week 48 ]
    To assess the effect of cotadutide versus placebo on improvement in fibrosis by at least one stage

  5. Part A: Absolute change from baseline in body weight [ Time Frame: Week 48 ]
    To determine whether cotadutide is superior to placebo for weight reduction

  6. Part A: Change from baseline in HbA1c in participants with T2DM [ Time Frame: Week 48 ]
    To determine whether cotadutide is superior to placebo for glycemic control in participants with T2DM

  7. Part A: Percent change from baseline in triglycerides [ Time Frame: Week 48 ]
    To assess the effect of cotadutide versus placebo on triglycerides

  8. Part B: Proportion of participants with ≥ 2-point improvement from baseline in NAS based on biopsy [ Time Frame: Week 84 ]
    To assess the effect of cotadutide versus placebo on ≥ 2-point improvement in NAS

  9. Part B: Proportion of participants with both resolution of NASH and improvement in fibrosis by at least one stage [ Time Frame: Week 84 ]
    To assess the effect of cotadutide versus placebo on resolution of NASH and improvement in fibrosis

  10. Part B: Proportion of participants with progression to cirrhosis based on biopsy [ Time Frame: Week 84 ]
    To assess the effect of cotadutide versus placebo on progression to cirrhosis

  11. Part B: Proportion of participants with improvement in fibrosis by at least one stage based on biopsy [ Time Frame: Week 84 ]
    To assess the effect of cotadutide versus placebo on improvement in fibrosis by at least one stage

  12. Part B: Absolute change from baseline in body weight [ Time Frame: Week 84 ]
    To determine whether cotadutide is superior to placebo for weight reduction

  13. Part B: Change from baseline in HbA1c in participants with T2DM [ Time Frame: Week 84 ]
    To determine whether cotadutide is superior to placebo for glycemic control in participants with T2DM

  14. Part B: Percent change from baseline in triglycerides [ Time Frame: Week 84 ]
    To assess the effect of cotadutide versus placebo on triglycerides


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of informed consent
  2. Males and female participants ≥ 18 to ≤ 75 years of age (inclusive) at the time of signing the informed consent.

  3. Histologically confirmed non-alcoholic steatohepatitis (NASH) per NASH Clinical Research Network (CRN) criteria as diagnosed by histology from a liver biopsy performed ≤ 180 days from randomization and fulfilling all of the following histological criteria:

    1. NAS (Non-alcoholic Fatty Liver Disease Activity Score) ≥ 4 with a score of ≥ 1 for each component: steatosis, lobular inflammation, and ballooning
    2. Presence of fibrosis stage F2 or F3
  4. Women of childbearing potential, non-pregnant and nonbreastfeeding and using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study intervention.

Exclusion Criteria:

  1. Chronic liver disease of other etiologies.
  2. History of cirrhosis and/or hepatic decompensation, including evidence of portal hypertension (e.g. low platelet count, splenomegaly, ascites, history of hepatic encephalopathy, esophageal varices, or variceal bleeding).
  3. Clinically significant cardiovascular or cerebrovascular disease within 90 days prior to screening, including but not limited to, myocardial infarction, acute coronary syndrome, unstable angina pectoris, transient ischemic attack, or stroke, or participants who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 90 days or who are due to undergo these procedures at the time of screening
  4. History of malignant neoplasms within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or any in situ carcinoma.
  5. Participation in another clinical study with an investigational product administered within the last 30 days or 5 half-lives of the therapy (whichever is longer) at the time of screening or the time of the historical biopsy or concurrent participation in another interventional study of any kind or prior randomization in this study.
  6. Severe allergy/hypersensitivity to any of the proposed study treatments or excipients
  7. Contraindication to liver biopsy (eg, bleeding diathesis, such as hemophilia, suspected hemangioma, or suspected echinococcal infection) or inability to safely obtain a liver biopsy as determined by the investigator
  8. Severely uncontrolled hypertension defined as SBP ≥ 180 mmHg or DBP ≥ 110 mmHg on the average of 2 seated BP measurements after being at rest for at least 10 minutes at screening or randomization 9 Any positive results for human immunodeficiency virus infection, positive results for hepatitis B surface antigen or hepatitis C antibody test along with a positive HCV RNA test.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05364931


Locations
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Sponsors and Collaborators
AstraZeneca
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05364931    
Other Study ID Numbers: D5671C00006
2021-005484-53 ( EudraCT Number )
First Posted: May 6, 2022    Key Record Dates
Last Update Posted: May 3, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
NASH
fatty liver disease
non-alcoholic fatty liver
 NAS
liver fibrosis
Non-alcoholic steatohepatitis
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Fibrosis
 Pathologic Processes
Liver Diseases
Digestive System Diseases