Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With NASH

NCT02913105 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CLMB763X2201
• Study Type: interventional
• Target: 122
• Locations: 8 countries
• Sites: 30

Brief Summary

The purpose of the present study is to assess the effects of LMB763 with respect to safety, tolerability, and on markers of liver inflammation in patients with NASH

Conditions

Non-alcoholic Steatohepatitis NASH

Keywords

Non-alcoholic Steatohepatitis; NASH; Fatty liver disease

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment. No statistical analysis was planned for this primary outcome measure.

  From date of First Participant First Treatment until Last Patient Last Visit (up to Day 112 (End of Study (EOS))

• Change From Baseline in Alanine Aminotransferase (ALT) Levels

  ALT level assessment is one of the diagnostic parameters in Liver function test (LFT). Baseline was defined as the mean of ALT levels at baseline and pre-dose visits. Geometric Mean and Geometric Coefficient of Variation for change are based on log-transformed ratio to baseline (i.e., change from baseline in the log domain).

  Baseline to Day 84 (Week 12)

Secondary Outcomes (14)

• Observed Maximum Plasma Concentration (Cmax) of LMB763

  0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 42

• Time to Reach Maximum Concentration (Tmax) of LMB763

  0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 42

• Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of LMB763

  0 to 96 hours post-dose on Days 1 and 42

• Accumulation Ratio (Racc) of LMB763

  Day 42

• Change From Baseline in Percentage of Liver Fat as Measured by Magnetic Resonance Imaging (MRI)

  Baseline to Day 84 (Week 12)

Study Arms (2)

LMB763

EXPERIMENTAL

Oral dose once daily for 12 weeks (84 days)

Drug: LMB763

Placebo

PLACEBO COMPARATOR

Oral dose once daily for 12 weeks (84 days)

Drug: Placebo

Interventions

LMB763 DRUG

Hard Gelatin Capsules

LMB763

Placebo DRUG

Hard Gelatin Capsule

Placebo

Eligibility Criteria

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

You may qualify if:

• Male/female patients, 18 years or older
• Written informed consent
• Presence of NASH by histologic evidence (liver biopsy) and elevated alanine aminotransferase (ALT), OR phenotypic diagnosis of NASH based on elevated ALT, BMI and diagnosis of Type 2 diabetes mellitus

You may not qualify if:

• Current use of obeticholic acid (OCA)
• New initiation GLP-1 agonists such as liraglutide, exenatide , lixisenatide, albiglutide or dulaglutide within 3 months of screening
• Pregnant or nursing (lactating) women
• Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 5 days after stopping study medication
• Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening
• Clinical evidence of hepatic decompensation or severe liver impairment
• Previous diagnosis of other forms of chronic liver disease
• Uncontrolled diabetes mellitus
• History or current diagnosis of ECG abnormalities
• Patients with contraindications to MRI imaging

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (30)

Novartis Investigative Site

Culver City, California, 90230, United States

Location

Novartis Investigative Site

Cypress, California, 90630, United States

Location

Novartis Investigative Site

Gainesville, Florida, 32610-0277, United States

Location

Novartis Investigative Site

Miami Springs, Florida, 33166, United States

Location

Novartis Investigative Site

Orlando, Florida, 32803, United States

Location

Novartis Investigative Site

Orlando, Florida, 32806, United States

Location

Novartis Investigative Site

Honolulu, Hawaii, 96814, United States

Location

Novartis Investigative Site

Baton Rouge, Louisiana, 70808, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02114, United States

Location

Novartis Investigative Site

High Point, North Carolina, 27265, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37211, United States

Location

Novartis Investigative Site

Arlington, Texas, 76012, United States

Location

Novartis Investigative Site

Houston, Texas, 77081, United States

Location

Novartis Investigative Site

Newport News, Virginia, 23602, United States

Location

Novartis Investigative Site

New Lambton, New South Wales, 2305, Australia

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Tbilisi, 0112, Georgia

Location

Novartis Investigative Site

Amman, 11941, Jordan

Location

Novartis Investigative Site

Papatoetoe, Auckland, 2025, New Zealand

Location

Novartis Investigative Site

Auckland, New Zealand

Location

Novartis Investigative Site

Christchurch, 8024, New Zealand

Location

Novartis Investigative Site

Tauranga, 3110, New Zealand

Location

Novartis Investigative Site

Wellington, 6021, New Zealand

Location

Novartis Investigative Site

San Juan, 00927, Puerto Rico

Location

Novartis Investigative Site

Bern, 3010, Switzerland

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

Novartis Investigative Site

Lugano, 6900, Switzerland

Location

Novartis Investigative Site

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Novartis Investigative Site

Glasgow, G31 2ER, United Kingdom

Location

Novartis Investigative Site

Portsmouth, PO6 3LY, United Kingdom

Location

Related Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Publication Agreements

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

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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: September 23, 2016
• Study Start: October 24, 2016
• Primary Completion: September 19, 2018
• Study Completion: September 19, 2018
• Last Updated: January 5, 2021
• Results First Posted: November 26, 2019

Record last verified: 2020-01

Locations

AU (2); CH (3); JO (1); GE (1); PR (1); GB (3); NZ (5); US (14)