Non-alcoholic Steatohepatitis NASHPhase 2NCT02913105
Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With NASH
A Phase 2 study testing LMB763 in people with Non-alcoholic Steatohepatitis NASH, run by Novartis Pharmaceuticals at 30 sites in 8 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-alcoholic Steatohepatitis NASH
- What is being tested?
- LMB763
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 30 sitesin 8 countries
- Study dates
- 24 Oct 2016to 19 Sep 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
30 sites in 8 countries.
30 sites in 8 countries
United States14 sites
Novartis Investigative Site
Arlington, Texas, 76012
Novartis Investigative Site
Baton Rouge, Louisiana, 70808
Novartis Investigative Site
Boston, Massachusetts, 02114
Novartis Investigative Site
Culver City, California, 90230
Novartis Investigative Site
Cypress, California, 90630
Novartis Investigative Site
Gainesville, Florida, 32610-0277
Novartis Investigative Site
High Point, North Carolina, 27265
Novartis Investigative Site
Honolulu, Hawaii, 96814
Novartis Investigative Site
Houston, Texas, 77081
Novartis Investigative Site
Miami Springs, Florida, 33166
Novartis Investigative Site
Nashville, Tennessee, 37211
Novartis Investigative Site
Newport News, Virginia, 23602
Novartis Investigative Site
Orlando, Florida, 32803
Novartis Investigative Site
Orlando, Florida, 32806
New Zealand5 sites
Novartis Investigative Site
Auckland
Novartis Investigative Site
Christchurch, 8024
Novartis Investigative Site
Papatoetoe, Auckland, 2025
Novartis Investigative Site
Tauranga, 3110
Novartis Investigative Site
Wellington, 6021
Switzerland3 sites
Novartis Investigative Site
Bern, 3010
Novartis Investigative Site
Geneva, 1211
Novartis Investigative Site
Lugano, 6900
United Kingdom3 sites
Novartis Investigative Site
Glasgow, G31 2ER
Novartis Investigative Site
Plymouth, Devon, PL6 8DH
Novartis Investigative Site
Portsmouth, PO6 3LY
Australia2 sites
Novartis Investigative Site
Nedlands, Western Australia, 6009
Novartis Investigative Site
New Lambton, New South Wales, 2305
About this study
Official title: A Randomized, Patient and Investigator Blinded, Placebo Controlled, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With Non-alcoholic Steatohepatitis (NASH)
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
- Being tested
- LMB763, Placebo
- Keywords
- Non-alcoholic Steatohepatitis, NASH, Fatty liver disease
- 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.
LMB763Drug
Hard Gelatin Capsules
PlaceboDrug
Hard Gelatin Capsule
| Study group | Role | What they receive |
|---|---|---|
| LMB763 | Experimental | Oral dose once daily for 12 weeks (84 days) Receives: Drug: LMB763 |
| Placebo | Placebo comparator | Oral dose once daily for 12 weeks (84 days) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: Baseline to Day 84 (Week 12)
Secondary outcomes (14)
Observed Maximum Plasma Concentration (Cmax) of LMB763
No statistical analysis was planned for this outcome measure.
Measured: 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
No statistical analysis was planned for this outcome measure.
Measured: 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
No statistical analysis was planned for this outcome measure.
Measured: 0 to 96 hours post-dose on Days 1 and 42
Accumulation Ratio (Racc) of LMB763
The drug accumulation ratio (Racc) is the ratio of accumulation of drug going from a single dose to steady state with repeated administration.
No statistical analysis was planned for this outcome measure.
Measured: Day 42
Change From Baseline in Percentage of Liver Fat as Measured by Magnetic Resonance Imaging (MRI)
Participants were to undergo MRI twice (Baseline and End of Treatment) during the course of the study to quantitate liver fat. Baseline was defined as the last available measurement prior to the first dose. 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).
Measured: Baseline to Day 84 (Week 12)
Change From Baseline in Weight
Baseline was defined as the last available measurement prior to the first dose.
Measured: Baseline to Days 28, 42, 56, 84 and 112 (EOS)
Change From Baseline in Body Mass Index (BMI)
Baseline was defined as the last available measurement prior to the first dose at specified visit (day).
Measured: Baseline to Days 28, 42, 56, 84 and 112 (EOS)
Change From Baseline in Waist to Hip Ratio
Baseline was defined as the last available measurement prior to the first dose.
Measured: Baseline to Days 28, 42, 56, 84 and 112 (EOS)
Change From to Baseline in Liver Stiffness
Fibroscan® was performed where available to assess liver stiffness. Baseline was defined as the last available measurement prior to the first dose. 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).
Measured: Baseline to Day 84 (Week 12)
Change From Baseline in Enhanced Liver Fibrosis (ELF) Test Panel
The ADVIA CentaurR systems' ELF™ test is an in vitro diagnostic multivariate index assay that provides a single score by combining quantitative measurements of hyaluronic acid (HA), amino-terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in human serum using the ADVIA Centaur XP, ADVIA Centaur XPT, and ADVIA Centaur CP systems in an algorithm. ELF score for the ADVIA Centaur systems is calculated by, first obtaining results for the ADVIA Centaur HA, PIIINP, and TIMP-1 assays and then using the following equation/algorithm:
ADVIA Centaur XP/XPT:
ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln(CP3NP) + 0.394 ln(CTIMP1)
ADVIA Centaur CP:
ELF score = 2.494 + 0.846 ln(CHA) + 0.735 ln(CP3NP) + 0.391 ln(CTIMP1) Concentrations (C) of each assay are in ng/mL
Interpretation of ELF score is as follows:
< 7.7 None to mild
- 7.7 to < 9.8 Moderate
- 9.8 Severe
Measured: Baseline to Days 42 and 84
Change From Baseline in Fibrosis Biomarker Test
Fibrosis Biomarker test included hyaluronic acid (HA), amino-terminal pro-peptide of procollagen type III (PIIINP), and tissue inhibitor of metalloproteinases (TIMP-1) as markers of liver fibrosis. Baseline was defined as the last available measurement prior to the first dose. 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).
Measured: Baseline to Days 42 and 84
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG)
Lipid measurements were collected under fasted conditions. Baseline was defined as the last available measurement prior to the first dose. 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).
Measured: Baseline to Days 7, 14, 28, 42, 56, 84 and 112 (EOS)
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol
Baseline was defined as the last available measurement prior to the first dose. 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).
Measured: Baseline to Days 7, 14, 28, 42, 56, 84 and 112 (EOS)
Change From Baseline in Visual Analog Scale (VAS) for Itching of Skin
A 10 cm VAS was used to assess the severity of participants itch (ranging from 0 = no itch at all to 10 = the worst imaginable itch). The score (distance from left) on the VAS was recorded by the participant marking with a line and used to test for an effect of LMB763 over placebo. Baseline was defined as the last available measurement prior to the first dose. A positive change from Baseline indicates improvement.
Measured: Baseline to Day 84 (Week 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study start24 Oct 2016
- Primary completion19 Sep 2018
- Study completion19 Sep 2018
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.
- Other trials for Non-alcoholic Steatohepatitis NASHStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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, Care provider, Investigator
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02913105
- Sponsor's protocol ID
- CLMB763X2201
- Status last verified
- Jan 2020
- First submitted
- 13 Sep 2016
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Patient and Investigator Blinded, Placebo Controlled, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With Non-alcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT02913105
- Acronym / sponsor ID
- CLMB763X2201
- Conditions
- Non-alcoholic Steatohepatitis NASH
- Keywords
- Non-alcoholic Steatohepatitis, NASH, Fatty liver disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Oct 2016 (actual)
- Primary completion
- 19 Sep 2018 (actual)
- Study completion
- 19 Sep 2018 (actual)
- First posted
- 23 Sep 2016 (estimated)
- Results
- Posted 26 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LMB763 | Experimental | Drug: LMB763Oral dose once daily for 12 weeks (84 days) |
| Placebo | Placebo comparator | Drug: PlaceboOral dose once daily for 12 weeks (84 days) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| LMB763Hard Gelatin Capsules | Drug | LMB763 |
| PlaceboHard Gelatin Capsule | Drug | Placebo |
Primary outcome
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From date of First Participant First Treatment until Last Patient Last Visit (up to Day 112 (End of Study (EOS))
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.
Change From Baseline in Alanine Aminotransferase (ALT) Levels
Time frame: Baseline to Day 84 (Week 12)
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).
14 secondary outcomes
Observed Maximum Plasma Concentration (Cmax) of LMB763
Time frame: 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
Time frame: 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
Time frame: 0 to 96 hours post-dose on Days 1 and 42
Accumulation Ratio (Racc) of LMB763
Time frame: Day 42
Change From Baseline in Percentage of Liver Fat as Measured by Magnetic Resonance Imaging (MRI)
Time frame: Baseline to Day 84 (Week 12)
Change From Baseline in Weight
Time frame: Baseline to Days 28, 42, 56, 84 and 112 (EOS)
Change From Baseline in Body Mass Index (BMI)
Time frame: Baseline to Days 28, 42, 56, 84 and 112 (EOS)
Change From Baseline in Waist to Hip Ratio
Time frame: Baseline to Days 28, 42, 56, 84 and 112 (EOS)
Change From to Baseline in Liver Stiffness
Time frame: Baseline to Day 84 (Week 12)
Change From Baseline in Enhanced Liver Fibrosis (ELF) Test Panel
Time frame: Baseline to Days 42 and 84
Change From Baseline in Fibrosis Biomarker Test
Time frame: Baseline to Days 42 and 84
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG)
Time frame: Baseline to Days 7, 14, 28, 42, 56, 84 and 112 (EOS)
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol
Time frame: Baseline to Days 7, 14, 28, 42, 56, 84 and 112 (EOS)
Change From Baseline in Visual Analog Scale (VAS) for Itching of Skin
Time frame: Baseline to Day 84 (Week 12)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
30 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LMB763 in people with Non-alcoholic Steatohepatitis NASH, run by Novartis Pharmaceuticals at 30 sites in 8 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 3 inclusion and 10 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: stopped early, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, New Zealand, Switzerland, United Kingdom, Australia and 3 more countries. 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 26 Nov 2019). 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?
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From date of First Participant First Treatment until Last Patient Last Visit (up to Day 112 (End of Study (EOS))). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jan 2021.