A Study to (1) Compare How BI 456906 is Taken up in the Body of Healthy People and People With Liver Problems and (2) Find Out How People With Overweight and Obesity, With and Without Liver Problems, Tolerate Different Doses of BI 456906

A Non-randomised, Open-label, 2-part, Parallel-cohort Trial to Evaluate 1) Pharmacokinetics, Safety, and Tolerability of a Single Subcutaneous Dose of BI 456906 in Patients With Cirrhosis and Varying Degrees of Hepatic Impairment Relative to Healthy Subjects With and Without Overweight/Obesity and 2) Safety and Tolerability of Multiple Subcutaneous Doses of BI 456906 in Patients With Overweight/Obesity With Cirrhosis and Varying Degrees of Hepatic Impairment Relative to Patients With Overweight/Obesity Without Cirrhosis/Hepatic Impairment

This study is open to adults who have different levels of liver problems and adults who are healthy. People with or without overweight or obesity can take part.

This study has 2 parts. The purpose of Part 1 is to find out whether having liver problems influences how BI 456906 is taken up in the body. The purpose of Part 2 is to find out whether having liver problems influences how people with overweight and obesity tolerate different doses of BI 456906.

In Part 1, participants get a single injection of BI 456906 under their skin and stay at the study site for 2 nights afterwards. They are in the study for about a month. During this time, they visit the study site about 8 more times. The doctors compare the amount of BI 456906 in the blood of healthy people and people with liver problems.

In Part 2, participants get 1 or 2 injections of BI 456906 once a week under their skin for 28 weeks. At the beginning, they get lower doses of BI 456906. Over time, they get higher doses until they reach a certain dose of BI 456906. This dose is then maintained until the end of the treatment. Participants in Part 2 are in the study for about 7 months. During this time, they visit the study site about 16 times and get about 15 phone calls from the site staff. The doctors record the number of people with health problems that could have been caused by treatment with BI 456906. They compare the results between participants with liver problems and those without liver problems.

In both parts, doctors also regularly check participants' health and take note of any unwanted effects.

Study Overview

• Status: Completed
• Conditions: Liver Diseases; Healthy; Obesity
• Intervention / Treatment: Drug: BI 456906

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Boehringer Ingelheim; Phone Number: 1-800-243-0127; Email: clintriage.rdg@boehringer-ingelheim.com

Study Locations

• Germany
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn AöR
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis University
  • Kistarcsa, Hungary, 2140
    • CRU Hungary Ltd.
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research (NZCR)
• Poland
  • Wroclaw, Poland, 51162
    • Dr. Piotr Napora, Center of Clinical Research
• Slovakia
  • Bratislava, Slovakia, 83101
    • Summit Clinical Research, s.r.o.
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Covenant Metabolic Specialists, LLC
    • Sarasota, Florida, United States, 34240
      • Covenant Metabolic Specialists, LLC
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the Texas Liver Institute
    • San Antonio, Texas, United States, 78229
      • IMA Clinical Research San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria -Part A:

• Male or female subjects with age ≥18 years (or the minimum country specific age of consent if >18 years) and 75 years, inclusive at the screening visit.
• Body mass index (BMI) of 18.5-40.0 kg/m2 (inclusive).
• Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
• Women of childbearing potential must be willing and able to use two forms of effective contraception where at least one form is highly effective method of birth control per ICH M3 (R2) that results in a low failure rate (i.e. <1% per year when used consistently and correctly). A list of contraception methods meeting these criteria is provided in the subject information. Please note that oral contraceptives are not allowed during the treatment period.

A woman is considered of childbearing potential, 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.

Further inclusion criteria apply.

-Part B:

• Male or female subjects between the ages of ≥18 (or the minimum country specific age of consent if >18 years) and 75 years, inclusive, at the screening visit.
• Subjects with overweight or obesity, defined as BMI ≥27 kg/m2 at the screening visit.
• A minimum absolute body weight of 70 kg for females and 80 kg for males at the screening visit.
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

Further inclusion criteria apply.

Exclusion criteria -Part A:

• Estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula).
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at screening.
• Calcitonin ≥20 pg/mL (5.84 pmol/L) at the screening visit.
• History of chronic or acute pancreatitis or elevation of serum lipase/amylase >2×ULN, or fasting serum triglyceride levels of >500 mg/dL (>5.65 mmol/L) at screening.

Further exclusion criteria apply.

-Part B:

• Prior surgery of the gastrointestinal tract that could interfere with body weight (including minimally invasive/endoscopic bariatric devices, bariatric surgery including metabolic operation that involves resection and/or reconstruction of any portion of the gastrointestinal tract) except appendectomy and simple hernia repair before randomization. However, a subject previously treated with reversible weight loss devices such as gastric banding, or intragastric balloon and removed longer than 12 months before screening should not be excluded.
• Glycosylated Hemoglobin, Type A1 (HbA1c) ≥11% at screening or diagnosed with type 1 diabetes mellitus.
• Exposure to Glucagon-like-peptide 1 (GLP-1) receptor agonist-based therapies (within 3 months prior to screening or within 5 half-lives of the drug, whichever is longer).
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at screening.

Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: BI 456906: Cohort 1; Healthy subjects	Drug: BI 456906; BI 456906
Experimental: Part A: BI 456906: Cohort 2; Patients with cirrhosis + Child-Turcotte-Pugh (CTP) Class A	Drug: BI 456906; BI 456906
Experimental: Part A: BI 456906: Cohort 3; Patients with cirrhosis + CTP Class B	Drug: BI 456906; BI 456906
Experimental: Part A: BI 456906: Cohort 4; Patients with cirrhosis + CTP Class C	Drug: BI 456906; BI 456906
Experimental: Part B: BI456906: Cohort 1; Patients with overweight/obesity without cirrhosis/hepatic impairment	Drug: BI 456906; BI 456906
Experimental: Part B: BI456906: Cohort 2; Patients with overweight/obesity with cirrhosis + CTP Class A	Drug: BI 456906; BI 456906
Experimental: Part B: BI456906: Cohort 3; Patients with overweight/obesity with cirrhosis + CTP Class B	Drug: BI 456906; BI 456906

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A: Area under the concentration-time curve of BI 456906 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)	Up to 360 hours
Part A: Maximum measured concentration of BI 456906 in plasma (Cmax)	Up to 360 hours
Part B: Percentage of patients treated who experience treatment-emergent adverse event	Up to Day 218

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A: Percentage of patients treated who experience treatment-emergent adverse event	Up to Day 35

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Zealand Pharma

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2022
• Primary Completion (Actual): December 29, 2023
• Study Completion (Actual): December 29, 2023

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): March 25, 2022

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Liver Diseases; Obesity; Overweight
• Other Study ID Numbers: 1404-0010; 2021-006247-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No