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    The EU Clinical Trials Register currently displays   43691   clinical trials with a EudraCT protocol, of which   7246   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2021-005484-53
    Sponsor's Protocol Code Number:D5671C00006
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2022-03-30
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2021-005484-53
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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
    A.3.2Name or abbreviated title of the trial where available
    PROXYMO-ADVANCE
    A.4.1Sponsor's protocol code numberD5671C00006
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca
    B.5.2Functional name of contact pointClinical Study Information Center
    B.5.3 Address:
    B.5.3.1Street AddressN/A
    B.5.3.2Town/ cityN/A
    B.5.3.3Post codeN/A
    B.5.3.4CountryUnited States
    B.5.6E-mailinformation.center@astrazeneca.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCotadutide
    D.3.4Pharmaceutical form Solution for injection in pre-filled pen
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCotadutide
    D.3.9.1CAS number 1686108-82-6
    D.3.9.2Current sponsor codeMEDI0382
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCotadutide
    D.3.4Pharmaceutical form Solution for injection in pre-filled pen
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCotadutide
    D.3.9.1CAS number 1686108-82-6
    D.3.9.2Current sponsor codeMEDI0382
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection in pre-filled pen
    D.8.4Route of administration of the placeboSubcutaneous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection in pre-filled pen
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Non-cirrhotic non-alcoholic steatohepatitis with fibrosis
    E.1.1.1Medical condition in easily understood language
    Non-alcoholic steatohepatitis
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 24.1
    E.1.2Level LLT
    E.1.2Classification code 10086370
    E.1.2Term NASH with fibrosis
    E.1.2System Organ Class 100000004871
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part A:

    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

    Part B:

    To determine whether cotadutide is superior to placebo on:
    - Resolution of NASH without worsening of liver fibrosis
    - Improvement of liver fibrosis by at least one stage without worsening of NASH
    E.2.2Secondary objectives of the trial
    Part A: To compare:
    1. cotadutide versus placebo on improvement in fibrosis by at least one stage without worsening of NASH
    2. cotadutide versus placebo on ≥ 2-point improvement in NAS
    3. cotadutide versus placebo on resolution of NASH and improvement in fibrosis
    4. cotadutide versus placebo on improvement in fibrosis by at least one stage
    5. cotadutide versus placebo on weight reduction
    6. cotadutide versus placebo on glycemic control in participants with T2DM
    7. cotadutide versus placebo on triglycerides

    Part B: To compare:
    1. cotadutide versus placebo on ≥ 2-point improvement in NAS
    2. cotadutide versus placebo on resolution of NASH and improvement in fibrosis
    3. cotadutide versus placebo on progression to cirrhosis
    4. cotadutide versus placebo on improvement in fibrosis by at least one stage
    5. cotadutide versus placebo on weight reduction
    6. cotadutide versus placebo on glycemic control in participants with T2DM
    7. cotadutide versus placebo on triglycerides
    E.2.3Trial contains a sub-study No
    E.3Principal 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:

    (a) NAS (Non-alcoholic Fatty Liver Disease Activity Score) ≥ 4 with a score of ≥
    1 for each component: steatosis, lobular inflammation, and ballooning

    (b) Presence of fibrosis stage F2 or F3

    4. Women of childbearing potential, non-pregnant and non-breastfeeding using at least one highly effective method of birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study intervention.
    E.4Principal 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.
    E.5 End points
    E.5.1Primary end point(s)
    Part A:

    • Proportion of participants with resolution of NASH without worsening of liver fibrosis based on biopsy at Week 48

    Part B:

    • Proportion of participants with resolution of NASH without worsening of liver fibrosis based on biopsy at Week 84
    • Proportion of participants with improvement of liver fibrosis by at least one stage without worsening of NASH based on biopsy at Week 84
    E.5.1.1Timepoint(s) of evaluation of this end point
    Part A:

    At Week 48

    Part B:

    At week 84
    E.5.2Secondary end point(s)
    Part A:

    • Proportion of participants with improvement of liver fibrosis by at least one stage without worsening of NASH based on biopsy at Week 48
    • Proportion of participants with ≥ 2-point improvement from baseline in NAS based on biopsy at week 48
    • Proportion of participants with both resolution of NASH and improvement in fibrosis by at least one stage based on biopsy at Week 48
    • Proportion of participants with improvement in fibrosis by at least one stage based on biopsy at week 48
    • Absolute change from baseline in body weight at Week 48
    • Change from baseline in HbA1c in participants with T2DM at Week 48
    • Percent change from baseline in triglycerides at Week 48

    Part B:

    • Proportion of participants with ≥ 2-point improvement from baseline in NAS based on biopsy at week 84
    • Proportion of participants with both resolution of NASH and improvement in fibrosis by at least one stage based on biopsy at Week 84
    • Proportion of participants with progression to cirrhosis based on biopsy at week 84
    • Proportion of participants with improvement in fibrosis by at least one stage based on biopsy at week 84
    • Absolute change from baseline in body weight at Week 84
    • Change from baseline in HbA1c in participants with T2DM at Week 84
    • Percent change from baseline in triglycerides at Week 84
    E.5.2.1Timepoint(s) of evaluation of this end point
    Part A:

    At Week 48

    Part B:

    At Week 84
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Dose adaptation design
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA80
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Brazil
    Canada
    Chile
    China
    Colombia
    Hong Kong
    Israel
    Japan
    Korea, Republic of
    Malaysia
    Mexico
    New Zealand
    Peru
    Philippines
    Singapore
    South Africa
    Taiwan
    Thailand
    United States
    Viet Nam
    Switzerland
    Russian Federation
    Turkey
    Austria
    Belgium
    France
    Germany
    Greece
    Hungary
    Italy
    Netherlands
    Spain
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study (both Part A and Part B included) is defined as the date of the last visit of the last participant in the study.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months36
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months36
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 1300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 560
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 192
    F.4.2.2In the whole clinical trial 1860
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-05-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-06-20
    P. End of Trial
    P.End of Trial StatusCompleted
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