Non-alcoholic Fatty Liver Disease (NAFLD)Phase 2NCT04019561
A Study to Evaluate Safety and Pharmacodynamic Efficacy of 0382 in Obese Subjects With NAFLD/NASH.
A Phase 2 study testing MEDI0382 high dose and MEDI0382 low dose in people with Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH), run by MedImmune LLC at 27 sites in 2 countries.
Trial summary
A Phase 2 study with 4 treatment groups of two differing doses and matched placebos designed to evaluate the safety (including hepatic safety), tolerability and pharmacodynamic effects of two dose levels of MEDI0382 in obese subjects with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). Read more about this study
- Who is it for?
- Ages 18 to 101 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease (NAFLD), Non-alcoholic Steatohepatitis (NASH)
- What is being tested?
- MEDI0382 high dose and MEDI0382 low dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 27 sitesin 2 countries
- Study dates
- 23 Sep 2019to 6 May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 101 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent (with the exception of consent for future genetic and non genetic research) prior to performing any study-specific procedures, including screening evaluations.
- Subjects aged ≥ 18 years at the time of consent.
- Body mass index ≥ 30 kg/m2 at screening.
- HbA1c ≤ 9.5% (inclusive) at screening if T2DM present, managed by either diet and/or a stable dose of metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, sulphonylureas or acarbose (ie, no major dose adjustments in prior 3 months to screening).
- Definitive NAFLD / NASH with NASH activity score (NAS) ≥ 4 with ≥ 1 in each component (i.e. steatosis, lobular inflammation and ballooning), as diagnosed by liver biopsy within 6 months of screening with liver fibrosis stage F1, F2 or F3. The number of subjects with F1 will be capped at 25% in the study.
- Evidence of hepatic steatosis or liver fat (≥ 10%) by MRI.
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- Women of childbearing potential:
- Who are sexually active with a non-sterilized male partner must have used at least one highly effective method of contraception from screening, and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
- Must have a negative urine pregnancy test within 72 hours prior to the first dose of investigational product; and not be breastfeeding.
Who cannot join
- History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study.
- Liver disease of other etiologies (eg, alcoholic steatohepatitis; drug-induced, viral, or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha 1 antitrypsin deficiency; Wilson's disease) including positive results for hepatitis B surface antigen (HBsAg) or hepatitis C antibody tests (anti-HCV).
- History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy or variceal bleeding.
- Prior or planned liver transplantation.
- Alcohol consumption > 21 units of alcohol per week for men and > 14 units per week for women on average over a two-year time frame prior to baseline biopsy.
- Evidence of alcohol dependence as assessed by the Alcohol Use Disorder Identification Test (AUDIT) questionnaire at screening
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- A history of type 1 diabetes mellitus (T1DM), a history of diabetic ketoacidosis or current use of insulin-based therapies.
- Clinically significant inflammatory bowel disease or other severe disease or surgery affecting the upper GI tract (including bariatric surgery) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
- Physician-diagnosed diabetic subjects with clinically significant gastroparesis (as judged by the investigator) or those treated for gastroparesis within 6 months prior to screening
- History of > 5 kg weight loss in the last 6 months prior to screening or recent (within 3 months of screening) use of drugs approved for weight loss (eg, orlistat, bupropion / naltrexone, phentermine-topiramate, phentermine, lorcaserin), as well as those drugs used off-label.
- Clinically significant cardiovascular or cerebrovascular disease within the past 3 months, including but not limited to, myocardial infarction, acute coronary syndrome or stroke, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening.
- Severe congestive heart failure (New York Heart Association Class IV).
- History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer.
- History of substance dependence or a positive screen for drugs of abuse, likely to impact subject safety or compliance with study procedures, at the discretion of the investigator.
- History of psychosis or bipolar disorder. History of major depressive disorder within the past year with the subject being clinically unstable, or any history of suicide attempt or history of suicidal ideation within the past year.
- Recent (within 3 months of baseline biopsy) use of therapies associated with development of NAFLD (eg, systemic corticosteroids, methotrexate, tamoxifen, amiodarone, or long-term use of tetracyclines).
- Recent (within 3 months of baseline biopsy) use of obeticholic acid or other therapy under investigation for NASH.
- High dose vitamin E (> 400 IU) unless on a stable dose for at least 1 year prior to the baseline biopsy, and not initiated after the biopsy was taken.
- Recent (within 3 months of baseline biopsy) use of GLP-1 receptor agonist or GLP-1 receptor agonist containing therapies.
- Any subject who has received another investigational product as part of a clinical study within the last 30 days or 5 half-lives of the therapy (whichever is longer) at the time of screening. Any prior exposure to MEDI0382 is not permitted.
- Concurrent participation in another interventional study of any kind or repeat randomization in this study.
- Severe allergy/hypersensitivity to any of the proposed study treatments or excipients.
- Contra-indication to MRI: such as subjects with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field; subjects with history of extreme claustrophobia or subject cannot fit inside the MR scanner cavity.
- History of acute pancreatitis or current chronic pancreatitis. Subjects with serum triglyceride concentrations above 1000 mg/dL (11 mmol/L) at screening, as this can precipitate acute pancreatitis.
- Abnormal laboratory values including any of the following:
- AST or ALT > 5 × ULN.
- Impaired renal function defined as estimated glomerular filtration rate (eGFR) ≤ 30 mL/minute/1.73 m2 at screening (estimated according to chronic kidney disease epidemiology collaboration [CKD-EPI]).
- Albumin < 35 g/L.
- International normalized ratio (INR) > 1.3.
- Total Bilirubin (TBL) > 25 µmol/L in the absence of known Gilbert's disease.
- Platelets < 140-150,000/mm3
- Any other clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results as judged by the investigator.
- Severely uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 180 mm Hg and/or diastolic blood pressure (DBP) ≥ 110 mm Hg on the average of 2 seated measurements after being at rest for at least 10 minutes at screening or randomization.
- Basal calcitonin level > 50 ng/L at screening, or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2).
- Hemoglobinopathy, hemolytic anemia, or chronic anemia (hemoglobin concentration < 11.5 g/dL [115 g/L] for male subjects or < 10.5 g/dL [105 g/L] for female subjects) at screening, or any other condition known to interfere with interpretation of HbA1c measurements
- Any positive results for human immunodeficiency virus (HIV) infection.
- Any AstraZeneca, MedImmune, contract research organization (CRO), or study site employee, or close relatives of any of the aforementioned employees.
- Females who are pregnant or lactating.
Trial locations and contacts
27 sites in 2 countries.
27 sites in 2 countries
United States26 sites
Research Site
Blue Ash, Ohio, 45242
Research Site
Canoga Park, California, 91303
Research Site
Chattanooga, Tennessee, 37421
Research Site
Chula Vista, California, 91911
Research Site
Coronado, California, 92118
Research Site
Doral, Florida, 33166
Research Site
Durham, North Carolina, 27705
Research Site
Hialeah, Florida, 33016
Research Site
Houston, Texas, 77002
Research Site
Houston, Texas, 77084
Research Site
La Jolla, California, 92093
Research Site
Las Vegas, Nevada, 89104
Research Site
Las Vegas, Nevada, 89109
Research Site
Lincoln, California, 95648
Research Site
Los Angeles, California, 90057
Research Site
Marrero, Louisiana, 70072
Research Site
Miami, Florida, 33125
Research Site
Miami, Florida, 33189
Research Site
Montclair, California, 91763
Research Site
Palmetto Bay, Florida, 33157
Research Site
Richmond, Virginia, 23219
Research Site
San Antonio, Texas, 78215
Research Site
San Antonio, Texas, 78229
Research Site
Torrance, California, 90505
Research Site
Tucson, Arizona, 85712
Research Site
Westminster, California, 92683
About this study
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Pharmacodynamic Effects of MEDI0382 in Obese Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)/ Non-Alcoholic Steatohepatitis (NASH)
A Phase 2 study with 4 treatment groups of two differing doses and matched placebos designed to evaluate the safety (including hepatic safety), tolerability and pharmacodynamic effects of two dose levels of MEDI0382 in obese subjects with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). The subjects will have biopsy-confirmed NAFLD/NASH with liver fibrosis stage F1, F2 or F3. Approximately 72 subjects will be randomized
Read the detailed description
This is a randomized, double-blind, placebo-controlled, study to evaluate the safety (including hepatic safety), tolerability and pharmacodynamic effects of two dose levels of MEDI0382 in obese subjects with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). The subjects will have biopsy-confirmed NAFLD/NASH with liver fibrosis stage F1, F2 or F3. Approximately 72 subjects will be randomized across multiple study sites.
- Being tested
- MEDI0382 high dose, Placebo for MEDI0382 high dose, MEDI0382 low dose, Placebo for MEDI0382 low dose
- Keywords
- Non-alcoholic fatty liver disease, NAFLD, Non-alcoholic steatohepatitis, NASH, 0382
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI0382 high doseDrug
Also called Cotadutide high dose
MEDI0382 high dose administered subcutaneously
Placebo for MEDI0382 high doseDrug
Also called Placebo high dose
Placebo for MEDI0382 high dose administered subcutaneously
MEDI0382 low doseDrug
Also called Cotadutide low dose
MEDI0382 low dose administered subcutaneously
Placebo for MEDI0382 low doseDrug
Also called Placebo low dose
Placebo for MEDI0382 low dose administered subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| MEDI0382 high dose | Experimental | MEDI0382 high dose administered subcutaneously Receives: Drug: MEDI0382 high dose |
| Placebo for MEDI0382 high dose | Placebo comparator | Placebo for MEDI0382 high dose administered subcutaneously Receives: Drug: Placebo for MEDI0382 high dose |
| MEDI0382 low dose | Experimental | MEDI0382 low dose administered subcutaneoously Receives: Drug: MEDI0382 low dose |
| Placebo for MEDI0382 low dose | Placebo comparator | Placebo for MEDI0382 low dose administered subcutaneously Receives: Drug: Placebo for MEDI0382 low dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (Including Hepatic Safety) and Tolerability of MEDI0382 Compared With Placebo: Number of Participants With TEAE and SAE
The number and percentage of treatment emergent adverse events (TEAE) and serious adverse events (SAE) through the end of the follow-up period
Measured: Day 1 - Day 161
Secondary outcomes (15)
Immunogenicity Profile Defined by Presence of Anti-drug Antibodies (ADA): ADA Titer (if Confirmed Positive)
Development of ADA titer (if confirmed positive)
Measured: Day 1 - Day 161 (Baseline, Week 6, Week 12, Week 16, Week 19 and Week 23)
Immunogenicity Profile Defined by Presence of Anti-drug Antibodies (ADA): Number of Participants With Development of ADA
Development of ADA during treatment and follow-up
Measured: Day 1 - Day 161
Change From Baseline to Week 19 in Hepatic Fat Fraction (HFF)
Change from baseline is defined as the week 19 post-baseline value minus the baseline value. The Analysis of Covariance (ANCOVA) model was used to fit change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Liver Volume
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Liver Fat Volume
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Visceral Adipose Tissue
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Subcutaneous Adipose Tissue
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Liver Diffusion
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Abdominal Sagittal Diameter
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Abdominal Transversal Diameter
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Alanine Aminotransferase (ALT)
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Gamma Glutamyl Transferase (GGT)
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Aspartate Aminotransferase (AST)
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Percent Change From Baseline to Week 19 in Body Weight
Percent change from baseline is calculated as the week 19 post-baseline value minus the baseline value divided by the baseline value *100. The Analysis of Covariance (ANCOVA) model was used to fit percent change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Change From Baseline to Week 19 in Body Mass Index (BMI)
Change from baseline is defined as the week 19 post-baseline value minus the baseline value. The Analysis of Covariance (ANCOVA) model was used to fit change at week 19. The group of treatment was considered as a fixed effect of the model while the baseline value as covariate. Last observation carried forward (LOCF) method was applied to handle missing data.
Measured: Baseline to week 19
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2019
- Study start23 Sep 2019
- Primary completion6 May 2021
- Study completion6 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-alcoholic Fatty Liver Disease (NAFLD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04019561
- Sponsor's protocol ID
- D5671C00002
- Status last verified
- Nov 2022
- First submitted
- 24 Jun 2019
- Last updated
- 17 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Shankar SS, Daniels SJ, Robertson D, Sarv J, Sanchez J, Carter D, Jermutus L, Challis B, Sanyal AJ. Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis. Clin Gastroenterol Hepatol. 2024 Sep;22(9):1847-1857.e11. doi: 10.1016/j.cgh.2024.04.017. Epub 2024 May 9.
PubMed 38729399
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Pharmacodynamic Effects of MEDI0382 in Obese Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)/ Non-Alcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT04019561
- Acronym / sponsor ID
- D5671C00002
- Keywords
- Non-alcoholic fatty liver disease, NAFLD, Non-alcoholic steatohepatitis, NASH, 0382
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 23 Sep 2019 (actual)
- Primary completion
- 6 May 2021 (actual)
- Study completion
- 6 May 2021 (actual)
- First posted
- 15 Jul 2019 (actual)
- Results
- Posted 31 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 2 study with 4 treatment groups of two differing doses and matched placebos designed to evaluate the safety (including hepatic safety), tolerability and pharmacodynamic effects of two dose levels of MEDI0382 in obese subjects with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). The subjects will have biopsy-confirmed NAFLD/NASH with liver fibrosis stage F1, F2 or F3. Approximately 72 subjects will be randomized
Detailed description
This is a randomized, double-blind, placebo-controlled, study to evaluate the safety (including hepatic safety), tolerability and pharmacodynamic effects of two dose levels of MEDI0382 in obese subjects with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). The subjects will have biopsy-confirmed NAFLD/NASH with liver fibrosis stage F1, F2 or F3. Approximately 72 subjects will be randomized across multiple study sites.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MEDI0382 high dose | Experimental | Drug: MEDI0382 high doseMEDI0382 high dose administered subcutaneously |
| Placebo for MEDI0382 high dose | Placebo comparator | Drug: Placebo for MEDI0382 high dosePlacebo for MEDI0382 high dose administered subcutaneously |
| MEDI0382 low dose | Experimental | Drug: MEDI0382 low doseMEDI0382 low dose administered subcutaneoously |
| Placebo for MEDI0382 low dose | Placebo comparator | Drug: Placebo for MEDI0382 low dosePlacebo for MEDI0382 low dose administered subcutaneously |
Who may qualify
- Ages
- 18 to 101 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Provision of informed consent (with the exception of consent for future genetic and non genetic research) prior to performing any study-specific procedures, including screening evaluations.
- Subjects aged ≥ 18 years at the time of consent.
- Body mass index ≥ 30 kg/m2 at screening.
- HbA1c ≤ 9.5% (inclusive) at screening if T2DM present, managed by either diet and/or a stable dose of metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, sulphonylureas or acarbose (ie, no major dose adjustments in prior 3 months to screening).
- Definitive NAFLD / NASH with NASH activity score (NAS) ≥ 4 with ≥ 1 in each component (i.e. steatosis, lobular inflammation and ballooning), as diagnosed by liver biopsy within 6 months of screening with liver fibrosis stage F1, F2 or F3. The number of subjects with F1 will be capped at 25% in the study.
Key exclusion criteria (38 listed)
- History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study.
- Liver disease of other etiologies (eg, alcoholic steatohepatitis; drug-induced, viral, or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha 1 antitrypsin deficiency; Wilson's disease) including positive results for hepatitis B surface antigen (HBsAg) or hepatitis C antibody tests (anti-HCV).
- History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy or variceal bleeding.
- Prior or planned liver transplantation.
- Alcohol consumption > 21 units of alcohol per week for men and > 14 units per week for women on average over a two-year time frame prior to baseline biopsy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI0382 high doseAlso: Cotadutide high doseMEDI0382 high dose administered subcutaneously | Drug | MEDI0382 high dose |
| Placebo for MEDI0382 high doseAlso: Placebo high dosePlacebo for MEDI0382 high dose administered subcutaneously | Drug | Placebo for MEDI0382 high dose |
| MEDI0382 low doseAlso: Cotadutide low doseMEDI0382 low dose administered subcutaneously | Drug | MEDI0382 low dose |
| Placebo for MEDI0382 low doseAlso: Placebo low dosePlacebo for MEDI0382 low dose administered subcutaneously | Drug | Placebo for MEDI0382 low dose |
Primary outcome
Safety (Including Hepatic Safety) and Tolerability of MEDI0382 Compared With Placebo: Number of Participants With TEAE and SAE
Time frame: Day 1 - Day 161
The number and percentage of treatment emergent adverse events (TEAE) and serious adverse events (SAE) through the end of the follow-up period
15 secondary outcomes
Immunogenicity Profile Defined by Presence of Anti-drug Antibodies (ADA): ADA Titer (if Confirmed Positive)
Time frame: Day 1 - Day 161 (Baseline, Week 6, Week 12, Week 16, Week 19 and Week 23)
Immunogenicity Profile Defined by Presence of Anti-drug Antibodies (ADA): Number of Participants With Development of ADA
Time frame: Day 1 - Day 161
Change From Baseline to Week 19 in Hepatic Fat Fraction (HFF)
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Liver Volume
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Liver Fat Volume
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Visceral Adipose Tissue
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Subcutaneous Adipose Tissue
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Liver Diffusion
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Abdominal Sagittal Diameter
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Abdominal Transversal Diameter
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Alanine Aminotransferase (ALT)
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Gamma Glutamyl Transferase (GGT)
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Aspartate Aminotransferase (AST)
Time frame: Baseline to week 19
Percent Change From Baseline to Week 19 in Body Weight
Time frame: Baseline to week 19
Change From Baseline to Week 19 in Body Mass Index (BMI)
Time frame: Baseline to week 19
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38729399Shankar SS, Daniels SJ, Robertson D, Sarv J, Sanchez J, Carter D, Jermutus L, Challis B, Sanyal AJ. Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis. Clin Gastroenterol Hepatol. 2024 Sep;22(9):1847-1857.e11. doi: 10.1016/j.cgh.2024.04.017. Epub 2024 May 9.
- d5671c00002-csp-amendment-6 - Redacted - 31Mar2022Link provided by the sponsor.
- d5671c00002-CSR-synopsis - Redacted - 31Mar2022Link provided by the sponsor.
- d5671c00002-sap-v5 - Redacted - 31Mar2022Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
RecruitingPhase 2
A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) Due to MASH
Metabolic Dysfunction-Associated Steatohepatitis, Non-alcoholic Fatty Liver Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
27 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MEDI0382 high dose and MEDI0382 low dose in people with Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH), run by MedImmune LLC at 27 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (Including Hepatic Safety) and Tolerability of MEDI0382 Compared With Placebo: Number of Participants With TEAE and SAE (time frame: Day 1 - Day 161). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04019561, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2023.