Non-alcoholic Fatty Liver DiseasePhase 2NCT03166735
Different Doses of BI 1467335 Compared to Placebo in Patients With Clinical Evidence of NASH
A Phase 2 study testing BI 1467335 in people with Non-alcoholic Fatty Liver Disease, run by Boehringer Ingelheim at 44 sites in 9 countries.
Trial summary
The primary objective of this study is the proof of mechanism and support of dose finding, together with the safety evaluation in patients with clinical evidence of NASH. To gain further insight into clinical effects of AOC3 inhibition on NASH further exploratory analyses of biomarkers related to NASH and liver… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- BI 1467335
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- 44 sitesin 9 countries
- Study dates
- 6 Jun 2017to 14 Jun 2019
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical evidence of NASH defined as a. histological evidence of NASH (no more than 3 years prior to screening) OR b. clinical imaging results suggestive of NASH (no more than 3 years prior to screening) OR within the screening phase, imaging procedures performed as per local standard) i. evidence of hepatic steatosis >5% measured by the MRI-PDFF) or assessed as moderate to severe steatosis (raised echogenicity of the liver parenchyma) by ultrasound AND ii. evidence of liver fibrosis defined as mean stiffness > 3.64 kPa as measured by the MRE protocol or mean stiffness > 7.2 kPa as measured by ultrasound based transient elastography (Fibroscan®)
- Increased ALT defined as a. ALT >1.5 ULN at screening and ALT >1.25 ULN in a local lab within 1 week to 3 months prior screening OR b. Historic ALT > 1.25 ULN more than 3 months prior to screening and two consecutive ALT > 1.5xULN must be confirmed at least 1 week apart within the screening period
- Age ≥ 18 and ≤75 years at screening
- BMI ≥25kg/m2 and <45kg/m2 at screening
- Stable body weight defined as less than 5% change in body weight in the 3 months prior to screening while being treated with the standard of care and not treated with anti-obesity medication at screening.
- Treatment with Antidiabetic concomitant medication including any insulin regimen needs to be stable for 3 months, and treatment with vitamin E needs to be stable for 6 months prior to informed consent and expected to be stable throughout the trial. All other concomitant medication has to be stable for at least 4 weeks prior screening. Concomitant medications taken to treat acute conditions (e.g. headache, sinusitis) for a short period (< 7 days) are permissible, if not otherwise prohibited.
- For female patients: Women of childbearing potential* can be randomized after a negative pregnancy test and under adequate contraception with two methods, of which at least one is highly effective, during the trial.* A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal ligation is NOT a method of permanent sterilisation. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
- Signed and dated written informed consent in accordance with GCP and local legislation prior to admission to the trial.
Who cannot join
- Current or history of significant alcohol consumption (defined as intake of >210g/week in males and >140g/week in females on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on investigator judgement.
- Prior participation in an interventional NASH trial 6 months before baseline or 5 times halflife of the investigational drug, whichever is longer.
- Prior or planned bariatric surgery during study conduct, except gastric-band surgery more than 2 years prior to screening (including adjustments) with a stable body weight within the last 12 months.
- Use of drugs historically associated with liver injury, hepatic steatosis or steatohepatitis in the 4 weeks prior to screening.
- History of liver cirrhosis (fibrosis stage 4), or hepatic decompensation (e.g. ascites, hepatic encephalopathy, variceal bleeding, etc.) or history of other forms of chronic liver disease (for example Hepatitis B, Hepatitis C, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilsons disease, hemochromatosis, A1At deficiency, history of liver transplantation).
- Active known chronic or relevant acute infections, such as HIV (Human Immunodeficiency Virus), \viral hepatitis, or tuberculosis. QuantiFERON® TB test and HBs Ag test will be performed during screening. Patients with a positive test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active infection.
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- Solid liver lesions other than haemangiomas.
- -- Suspicion or diagnosis or history of hepatocellular carcinoma (HCC)
- eGFR <60ml/min/1.73m2 at screening (CKD-EPI formula).
- ALT >5.0 ULN at screening.
- Platelet count < 150.000/μL
- Bilirubin level > ULN (except for known Gilbert´s disease with a conjugated bilirubin of < 0.3 mg/dL))
- Uncontrolled diabetes defined as an HbA1c ≥9.5% in the 3 months prior to or at screening.
- Diagnosis of a serious or unstable disease including hepatic (other than NASH), renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic , psychiatric, immunologic, or hematologic disease and other conditions that, in the clinical judgment of the investigator, are likely to interfere with the analyses of safety and efficacy in this study. Patients with an expected life expectancy of less than 2 years are also excluded.
- Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomisation or planned during study conduct, e.g. hip replacement.
- Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
- Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
- Previous randomisation in this trial.
- Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s).
- Chronic drug abuse or any condition that, in the investigator's opinion, makes them an unreliable study subject or unlikely to complete the trial.
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
- Patients with Wolff-Parkinson-White Syndrome, baseline QTc > 450 ms, family history of long QT, or on medication prolonging QT time at screening or planned initiation during the trial.
- Any other clinical condition that, in the opinion of the investigator, would jeopardize patient safety while participating in this clinical trial.
Trial locations and contacts
44 sites in 9 countries.
44 sites in 9 countries
United States17 sites
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Southern California Research Center
Coronado, California, 92118
Dallas Diabetes and Endocrine Center
Dallas, Texas, 75230
Duke University Medical Center
Durham, North Carolina, 27710
University of California San Diego
La Jolla, California, 92037
eStudySite
La Mesa, California, 91942
Florida Research Institute
Lakewood Rch, Florida, 34211
Pinnacle Clinical Research
Live Oak, Texas, 78233
National Research Institute
Los Angeles, California, 90057
National Research Institute
Los Angeles, California, 90255
Northwell Health
Manhasset, New York, 11030
Genoma Research Group, Inc
Miami, Florida, 33165
Diabetes and Endocrinology Consultants, PC
Morehead City, North Carolina, 28557
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901
Virginia Commonwealth University
Richmond, Virginia, 23298
American Research Corporation at the Texas Liver Institute
San Antonio, Texas, 78215
Quest Clinical Research
San Francisco, California, 94115
Germany6 sites
Universitätsklinikum Aachen, AöR
Aachen, 52074
Universitätsklinikum Köln (AöR)
Cologne, 50937
Universitätsklinikum Frankfurt
Frankfurt am Main, 60590
Universitätsklinikum Leipzig
Leipzig, 04103
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55131
Universitätsklinikum Würzburg
Würzburg, 97080
Spain5 sites
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Virgen de la Victoria
Málaga, 29010
Hospital Universitario Marqués de Valdecilla
Santander, 39008
Hospital Virgen del Rocío
Seville, 41013
Hospital General Universitario de Valencia
Valencia, 46014
Belgium4 sites
Edegem - UNIV UZ Antwerpen
Edegem, 2650
AZ Maria Middelares
Ghent, 9000
UZ Leuven
Leuven, 3000
Centre Hospitalier Universitaire de Liège
Liège, 4000
United Kingdom4 sites
Queen Elizabeth Hospital
Birmingham, B15 2TH
Aintree University Hospital
Liverpool, L9 7AL
Manchester Royal Infirmary
Manchester, M13 9WL
Royal Stoke University Hospital
Stoke-on-Trent, ST4 6QG
Netherlands3 sites
Amsterdam UMC, Locatie AMC
Amsterdam, 1105 AZ
Maastricht Universitair Medisch Centrum
Maastricht, 6229 HX
Radboud Universitair Medisch Centrum
Nijmegen, 6525 GA
Canada2 sites
University of Calgary
Calgary, Alberta, T2N 4Z6
Toronto Liver Centre
Toronto, Ontario, M6H 3M1
France2 sites
HOP Claude Huriez
Lille, 59037
HOP La Pitié Salpêtrière
Paris, 75651
About this study
Official title: A Multi-centre, Double-blind, Parallel-group, Randomised, Placebo Controlled Phase II a Study to Investigate Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Different Doses of Orally Administered BI 1467335 During a 12-week Treatment Period Compared to Placebo in Patients With Clinical Evidence of NASH.
The primary objective of this study is the proof of mechanism and support of dose finding, together with the safety evaluation in patients with clinical evidence of NASH.
To gain further insight into clinical effects of AOC3 inhibition on NASH further exploratory analyses of biomarkers related to NASH and liver fibrosis will be performed. This will include the effect of BI 1467335 on reduction of secondary biomarker endpoints (ALT, AST, AP, γ-GT and CK18 fragments). Safety will be assessed throughout the study to provide key information regarding the use of BI 1467335 in patients with NASH.
- Conditions
- Non-alcoholic Fatty Liver Disease
- Being tested
- BI 1467335, Placebo
- 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.
BI 1467335Drug
once daily
PlaceboDrug
once daily
| Study group | Role | What they receive |
|---|---|---|
| BI 1467335 dose 1 | Experimental | Not described Receives: Drug: BI 1467335 |
| BI 1467335 dose 2 | Experimental | Not described Receives: Drug: BI 1467335 |
| BI 1467335 dose 3 | Experimental | Not described Receives: Drug: BI 1467335 |
| BI 1467335 dose 4 | Experimental | Not described Receives: Drug: BI 1467335 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Amine Oxidase Copper-containing 3 (AOC3) Activity After 12 Weeks of Treatment, Relative to Baseline in Percent
The patient-specific plasma AOC3 activity at time t (24 hours after the last dose in week 12) relative to baseline in percentage was calculated as follows:
%AOC3at = [(AOC3at - AOC3at,back) ⁄ (AOC3abase - AOC3abase,back)]*100
With AOC3at the AOC3 activity measured at time t, AOC3at,back the background noise at time t, AOC3abase the AOC3 activity measured at baseline and AOC3abase,back the background noise at baseline.
A dose-response relationship was analysed using a non-linear regression model to estimate the daily dosage needed to reach 10% of AOC3 activity (i.e. 90% inhibition) 12 weeks after treatment.
Measured: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Secondary outcomes (7)
Percentage of Participants With Drug-related Adverse Events (AEs)
Percentage of participants with drug-related adverse events (AEs). Percentages are calculated using total number of patients per treatment as the denominator.
Measured: Start of treatment till end of treatment + 28 days, up to 113 days.
Alanine Aminotransaminase (ALT) After 12 Weeks of Treatment, Relative to Baseline in Percent
Alanine aminotransaminase (ALT) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints.
The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100%
Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.
Measured: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Aspartate Aminotransferase (AST) After 12 Weeks of Treatment, Relative to Baseline in Percent
Aspartate aminotransferase (AST) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints.
The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100%
Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.
Measured: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Alkaline Phosphatase (AP) After 12 Weeks of Treatment, Relative to Baseline in Percent
Alkaline phosphatase (AP) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints.
The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100%
Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.
Measured: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Gamma-glutamyltransferase (GGT) After 12 Weeks of Treatment, Relative to Baseline in Percent
Gamma-glutamyltransferase (GGT) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints.
The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100%
Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.
Measured: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Caspase-cleaved Cytokeratin 18 (CK-18 Caspase) After 12 Weeks of Treatment, Relative to Baseline in Percent
Caspase-cleaved cytokeratin 18 (CK-18 caspase) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints.
The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100%
Statistical analyses description: A MMRM over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.
Measured: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Total Cytokeratin 18 (CK-18 Total) After 12 Weeks of Treatment, Relative to Baseline in Percent
Total cytokeratin 18 (CK-18 total) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints.
The unit of measure is: percentage relative to baseline = [post baseline (time t)/baseline]*100%.
Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base*time' interaction, and 'treatment*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.
Measured: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2017
- Study start6 Jun 2017
- Primary completion14 Jun 2019
- Study completion14 Jun 2019
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 DiseaseStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03166735
- Sponsor's protocol ID
- 1386-0004
- Other IDs
- 2016-000499-83, 2016
- Status last verified
- May 2020
- First submitted
- 24 May 2017
- Last updated
- 11 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Newsome PN, Sanyal AJ, Neff G, Schattenberg JM, Ratziu V, Ertle J, Link J, Mackie A, Schoelch C, Lawitz E; BI 1467335 NASH Phase IIa trial team. A randomised Phase IIa trial of amine oxidase copper-containing 3 (AOC3) inhibitor BI 1467335 in adults with non-alcoholic steatohepatitis. Nat Commun. 2023 Nov 6;14(1):7151. doi: 10.1038/s41467-023-42398-w.
PubMed 37932258
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre, Double-blind, Parallel-group, Randomised, Placebo Controlled Phase II a Study to Investigate Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Different Doses of Orally Administered BI 1467335 During a 12-week Treatment Period Compared to Placebo in Patients With Clinical Evidence of NASH.
- ClinicalTrials.gov ID
- NCT03166735
- Acronym / sponsor ID
- 1386-0004
- Conditions
- Non-alcoholic Fatty Liver Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 6 Jun 2017 (actual)
- Primary completion
- 14 Jun 2019 (actual)
- Study completion
- 14 Jun 2019 (actual)
- First posted
- 25 May 2017 (actual)
- Results
- Posted 11 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is the proof of mechanism and support of dose finding, together with the safety evaluation in patients with clinical evidence of NASH.
To gain further insight into clinical effects of AOC3 inhibition on NASH further exploratory analyses of biomarkers related to NASH and liver fibrosis will be performed. This will include the effect of BI 1467335 on reduction of secondary biomarker endpoints (ALT, AST, AP, γ-GT and CK18 fragments). Safety will be assessed throughout the study to provide key information regarding the use of BI 1467335 in patients with NASH.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| BI 1467335 dose 1 | Experimental | Drug: BI 1467335 |
| BI 1467335 dose 2 | Experimental | Drug: BI 1467335 |
| BI 1467335 dose 3 | Experimental | Drug: BI 1467335 |
| BI 1467335 dose 4 | Experimental | Drug: BI 1467335 |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Clinical evidence of NASH defined as a. histological evidence of NASH (no more than 3 years prior to screening) OR b. clinical imaging results suggestive of NASH (no more than 3 years prior to screening) OR within the screening phase, imaging procedures performed as per local standard) i. evidence of hepatic steatosis >5% measured by the MRI-PDFF) or assessed as moderate to severe steatosis (raised echogenicity of the liver parenchyma) by ultrasound AND ii. evidence of liver fibrosis defined as mean stiffness > 3.64 kPa as measured by the MRE protocol or mean stiffness > 7.2 kPa as measured by ultrasound based transient elastography (Fibroscan®)
- Increased ALT defined as a. ALT >1.5 ULN at screening and ALT >1.25 ULN in a local lab within 1 week to 3 months prior screening OR b. Historic ALT > 1.25 ULN more than 3 months prior to screening and two consecutive ALT > 1.5xULN must be confirmed at least 1 week apart within the screening period
- Age ≥ 18 and ≤75 years at screening
- BMI ≥25kg/m2 and <45kg/m2 at screening
- Stable body weight defined as less than 5% change in body weight in the 3 months prior to screening while being treated with the standard of care and not treated with anti-obesity medication at screening.
Key exclusion criteria (23 listed)
- Current or history of significant alcohol consumption (defined as intake of >210g/week in males and >140g/week in females on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on investigator judgement.
- Prior participation in an interventional NASH trial 6 months before baseline or 5 times halflife of the investigational drug, whichever is longer.
- Prior or planned bariatric surgery during study conduct, except gastric-band surgery more than 2 years prior to screening (including adjustments) with a stable body weight within the last 12 months.
- Use of drugs historically associated with liver injury, hepatic steatosis or steatohepatitis in the 4 weeks prior to screening.
- History of liver cirrhosis (fibrosis stage 4), or hepatic decompensation (e.g. ascites, hepatic encephalopathy, variceal bleeding, etc.) or history of other forms of chronic liver disease (for example Hepatitis B, Hepatitis C, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilsons disease, hemochromatosis, A1At deficiency, history of liver transplantation).
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 |
|---|---|---|
| BI 1467335once daily | Drug | BI 1467335 dose 1, BI 1467335 dose 2, BI 1467335 dose 3, BI 1467335 dose 4 |
| Placeboonce daily | Drug | Placebo |
Primary outcome
Plasma Amine Oxidase Copper-containing 3 (AOC3) Activity After 12 Weeks of Treatment, Relative to Baseline in Percent
Time frame: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
The patient-specific plasma AOC3 activity at time t (24 hours after the last dose in week 12) relative to baseline in percentage was calculated as follows: %AOC3at = [(AOC3at - AOC3at,back) ⁄ (AOC3abase - AOC3abase,back)]*100 With AOC3at the AOC3 activity measured at time t, AOC3at,back the background noise at time t, AOC3abase the AOC3 activity measured at baseline and AOC3abase,back the background noise at baseline. A dose-response relationship was analysed using a non-linear regression model to estimate the daily dosage needed to reach 10% of AOC3 activity (i.e. 90% inhibition) 12 weeks after treatment.
7 secondary outcomes
Percentage of Participants With Drug-related Adverse Events (AEs)
Time frame: Start of treatment till end of treatment + 28 days, up to 113 days.
Alanine Aminotransaminase (ALT) After 12 Weeks of Treatment, Relative to Baseline in Percent
Time frame: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Aspartate Aminotransferase (AST) After 12 Weeks of Treatment, Relative to Baseline in Percent
Time frame: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Alkaline Phosphatase (AP) After 12 Weeks of Treatment, Relative to Baseline in Percent
Time frame: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Gamma-glutamyltransferase (GGT) After 12 Weeks of Treatment, Relative to Baseline in Percent
Time frame: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Caspase-cleaved Cytokeratin 18 (CK-18 Caspase) After 12 Weeks of Treatment, Relative to Baseline in Percent
Time frame: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Total Cytokeratin 18 (CK-18 Total) After 12 Weeks of Treatment, Relative to Baseline in Percent
Time frame: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37932258Newsome PN, Sanyal AJ, Neff G, Schattenberg JM, Ratziu V, Ertle J, Link J, Mackie A, Schoelch C, Lawitz E; BI 1467335 NASH Phase IIa trial team. A randomised Phase IIa trial of amine oxidase copper-containing 3 (AOC3) inhibitor BI 1467335 in adults with non-alcoholic steatohepatitis. Nat Commun. 2023 Nov 6;14(1):7151. doi: 10.1038/s41467-023-42398-w.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
44 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BI 1467335 in people with Non-alcoholic Fatty Liver Disease, run by Boehringer Ingelheim at 44 sites in 9 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 8 inclusion and 23 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 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Germany, Spain, Belgium, United Kingdom and 4 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 11 Jun 2020). 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?
Plasma Amine Oxidase Copper-containing 3 (AOC3) Activity After 12 Weeks of Treatment, Relative to Baseline in Percent (time frame: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.). 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 NCT03166735, 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 11 Jun 2020.