Use of a Novel Drug in People With Non-alcoholic Steatohepatitis (NASH) or Non-alcoholic Fatty Liver Disease (NAFLD)

NCT02605616 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 15-000013
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

Does the novel drug decrease liver fat in subjects with NASH or NAFLD as compared to placebo

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Percentage Change in Hepatic Fat

  Percentage Hepatic fat measured using Magnetic Resonance Imaging (Proton Density Fat Fraction). A cut-off of \<5% is used to distinguish between normal and fatty liver.

  baseline, approximately 12 weeks

• Number of Participants With no Conversion of [13C] Cortisone to [13C] Cortisol

  Hepatic conversion of \[13C\] cortisone to \[13C\] cortisol was assessed before and after the treatment in both groups using the triple tracer cortisol test.

  baseline, approximately 12 weeks

Secondary Outcomes (2)

• Liver Fibrosis Measured With MRE in kPa

  baseline, approximately 12 weeks

• Total Insulin Sensitivity (Si) and Hepatic Insulin Sensitivity (Si Liver)

  baseline, approximately 12 weeks

Study Arms (2)

Active drug AZ compound

EXPERIMENTAL

AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).

Drug: AZ compound

Placebo

PLACEBO COMPARATOR

Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).

Other: Placebo

Interventions

AZ compound DRUG

AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).

Active drug AZ compound

Placebo OTHER

Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg).

Placebo

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 21-75
• Body Mass Index (BMI) \>19 kg/m\^2
• Subjects with biopsy/MRE proven NASH \[MRE liver fat ≥ 5%, with elevated liver enzymes ALT \<5x upper limit normal (ULN)\].
• Subjects with NAFLD and MRE shows F0 or greater fibrosis
• Subjects with history suggestive of NAFLD/NASH
• Total bilirubin must be \< 1.5 x ULN and INR must be \< 1.3 at baseline screening.
• TSH and CPK will be within normal limits (WNL) at screening.
• Subjects with type 2 diabetes who are on stable doses of medications (except pioglitazone) to control hyperglycemia and have baseline HbA1c of 10% or lower.
• Hemoglobin must be greater than or equal to 12.0 in males and 11.0 in females.

You may not qualify if:

• Medications that may affect glucose metabolism such as corticosteroids, opiates, barbiturates, and anticoagulants.
• Subjects with anemia, and symptoms suggestive of undiagnosed illness, overt hepatic disease, stroke, Alzheimer's disease, autoimmune hepatitis, alcoholism or increased alcohol consumption over the American Diabetes Association (ADA) guidelines.
• Any disorder that may potentially impact the outcome measures.
• Pregnant women and children.
• Subjects planning weight loss or in any weight loss program.
• Subjects taking TZD's, Atazanavir, Indinavir, Ketoconazole, Valproic acid, Silybum marianum and Valeriana officinalis.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• AstraZeneca: collaborator

Study Sites (1)

Yogesh Yadav

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

MeRho-Az compound

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Limitations and Caveats

The study was stopped after enrolling 93 patients. The sponsor recalled the batch of AZD4017 /placebo that was provided to the study investigator after the batch of the investigational product failed a routine stability retest that was performed to support potential shelflife extension. Ten patients who were taking either AZD4017 or a placebo were asked to stop taking their drug. Since eight of the10 patients were close to reaching study completion, their data were included in the ITT analyses.

Results Point of Contact

• Title: Dr. Rita Basu
• Organization: University of Virginia

rb4vd@virginia.edu

434-924-5183

Study Officials

• Rita Basu, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: November 16, 2015
• Study Start: November 1, 2015
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: March 1, 2024
• Results First Posted: April 4, 2022

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)