A Study to Evaluate Safety and Pharmacodynamic Efficacy of 0382 in Obese Subjects With NAFLD/NASH.

NCT04019561 | Completed Phase 2 Results FDA Drug

• 1 other identifier: D5671C00002
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 27

Brief 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). The subjects will have biopsy-confirmed NAFLD/NASH with liver fibrosis stage F1, F2 or F3. Approximately 72 subjects will be randomized

Conditions

Non-alcoholic Fatty Liver Disease (NAFLD); Non-alcoholic Steatohepatitis (NASH)

Keywords

Non-alcoholic fatty liver disease; NAFLD; Non-alcoholic steatohepatitis; NASH; 0382

Outcome Measures

Primary Outcomes (1)

• 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

  Day 1 - Day 161

Secondary Outcomes (15)

• Immunogenicity Profile Defined by Presence of Anti-drug Antibodies (ADA): ADA Titer (if Confirmed Positive)

  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

  Day 1 - Day 161

• Change From Baseline to Week 19 in Hepatic Fat Fraction (HFF)

  Baseline to week 19

• Percent Change From Baseline to Week 19 in Liver Volume

  Baseline to week 19

• Percent Change From Baseline to Week 19 in Liver Fat Volume

  Baseline to week 19

Study Arms (4)

MEDI0382 high dose

EXPERIMENTAL

MEDI0382 high dose administered subcutaneously

Drug: MEDI0382 high dose

Placebo for MEDI0382 high dose

PLACEBO COMPARATOR

Placebo for MEDI0382 high dose administered subcutaneously

Drug: Placebo for MEDI0382 high dose

MEDI0382 low dose

EXPERIMENTAL

MEDI0382 low dose administered subcutaneoously

Drug: MEDI0382 low dose

Placebo for MEDI0382 low dose

PLACEBO COMPARATOR

Placebo for MEDI0382 low dose administered subcutaneously

Drug: Placebo for MEDI0382 low dose

Interventions

MEDI0382 high dose DRUG

MEDI0382 high dose administered subcutaneously

Also known as: Cotadutide high dose

MEDI0382 high dose

Placebo for MEDI0382 high dose DRUG

Placebo for MEDI0382 high dose administered subcutaneously

Also known as: Placebo high dose

Placebo for MEDI0382 high dose

MEDI0382 low dose DRUG

MEDI0382 low dose administered subcutaneously

Also known as: Cotadutide low dose

MEDI0382 low dose

Placebo for MEDI0382 low dose DRUG

Placebo for MEDI0382 low dose administered subcutaneously

Also known as: Placebo low dose

Placebo for MEDI0382 low dose

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (27)

Research Site

Tucson, Arizona, 85712, United States

Location

Research Site

Canoga Park, California, 91303, United States

Location

Research Site

Chula Vista, California, 91911, United States

Location

Research Site

Coronado, California, 92118, United States

Location

Research Site

La Jolla, California, 92093, United States

Location

Research Site

Lincoln, California, 95648, United States

Location

Research Site

Los Angeles, California, 90057, United States

Location

Research Site

Montclair, California, 91763, United States

Location

Research Site

Torrance, California, 90505, United States

Location

Research Site

Westminster, California, 92683, United States

Location

Research Site

Doral, Florida, 33166, United States

Location

Research Site

Hialeah, Florida, 33016, United States

Location

Research Site

Miami, Florida, 33125, United States

Location

Research Site

Miami, Florida, 33189, United States

Location

Research Site

Palmetto Bay, Florida, 33157, United States

Location

Research Site

Marrero, Louisiana, 70072, United States

Location

Research Site

Las Vegas, Nevada, 89104, United States

Location

Research Site

Las Vegas, Nevada, 89109, United States

Location

Research Site

Durham, North Carolina, 27705, United States

Location

Research Site

Blue Ash, Ohio, 45242, United States

Location

Research Site

Chattanooga, Tennessee, 37421, United States

Location

Research Site

Houston, Texas, 77002, United States

Location

Research Site

Houston, Texas, 77084, United States

Location

Research Site

San Antonio, Texas, 78215, United States

Location

Research Site

San Antonio, Texas, 78229, United States

Location

Research Site

Richmond, Virginia, 23219, United States

Location

Research Site

San Juan, 00927, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 38729399 DERIVED

Related Links

• d5671c00002-csp-amendment-6 - Redacted - 31Mar2022
• d5671c00002-CSR-synopsis - Redacted - 31Mar2022
• d5671c00002-sap-v5 - Redacted - 31Mar2022

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

cotadutide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2019
• First Posted: July 15, 2019
• Study Start: September 23, 2019
• Primary Completion: May 6, 2021
• Study Completion: May 6, 2021
• Last Updated: January 17, 2023
• Results First Posted: May 31, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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 de-identified 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.

Locations

US (26); PR (1)