Clinical trial NCT05296733: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Liver Diseases
Obesity
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2022-03-25
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Area under the concentration-time curve of BI 456906 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
timeFrame: Up to 360 hours
measure: Part A: Maximum measured concentration of BI 456906 in plasma (Cmax)
timeFrame: Up to 360 hours
measure: Part B: Percentage of patients treated who experience treatment-emergent adverse event
timeFrame: Up to Day 218
Secondary outcomes:
measure: Part A: Percentage of patients treated who experience treatment-emergent adverse event
timeFrame: Up to Day 35
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Fort Myers
country: United States
facility: Covenant Metabolic Specialists, LLC
state: Florida
city: Sarasota
country: United States
facility: Covenant Metabolic Specialists, LLC
state: Florida
city: San Antonio
country: United States
facility: American Research Corporation at the Texas Liver Institute
state: Texas
city: San Antonio
country: United States
facility: IMA Clinical Research San Antonio
state: Texas
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn AöR
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Budapest
country: Hungary
facility: Semmelweis University
city: Kistarcsa
country: Hungary
facility: CRU Hungary Ltd.
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research (NZCR)
city: Wroclaw
country: Poland
facility: Dr. Piotr Napora, Center of Clinical Research
city: Bratislava
country: Slovakia
facility: SUMMIT CLINICAL RESEARCH, s.r.o.
Study officials:
References: