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.
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 114
- Locations
- 43
- Primary Endpoint
- Plasma Amine Oxidase Copper-containing 3 (AOC3) Activity After 12 Weeks of Treatment, Relative to Baseline in Percent
Study Overview
Brief 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 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
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
BI 1467335 dose 1
Intervention: BI 1467335 (Drug)
BI 1467335 dose 2
Intervention: BI 1467335 (Drug)
BI 1467335 dose 3
Intervention: BI 1467335 (Drug)
BI 1467335 dose 4
Intervention: BI 1467335 (Drug)
Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Percentage of Participants With Drug-related Adverse Events (AEs)(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(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(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(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(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(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(Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.)