A study to test whether BI 685509 alone or in combination with empagliflozin helps people with liver cirrhosis caused by viral hepatitis or non-alcoholic steatohepatitis (NASH) who have high blood pressure in the portal vein (main vessel going to the liver)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH, Boehringer Ingelheim Espana S.A., Boehringer Ingelheim RCV GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

28 Jul 2022 → 31 May 2024

Decision date (initial)

2023-05-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-504257-12-00

EudraCT number

2021-005171-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The trial will investigate the safety and tolerability of BI 685509 in patients with CSPH in compensated cirrhosis due to HBV, HCV and NASH with or without T2DM and the combination of BI 685509 and empagliflozin in patients with CSPH in compensated cirrhosis due to NASH with T2DM, on top of standard of care respectively. The primary objective is to estimate the percentage change in HVPG from baseline measured after 8 weeks. The primary analysis will be made for treated patients with baseline HVPG measurements (Full Analysis Set, FAS) as if all patients took treatment for the duration of the trial.

Conditions and MedDRA coding

Portal hypertension

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
2. Male or female who is ≥ 18 (or who is of legal age in countries where that is greater than 18) and ≤ 75 years old at screening
3. Clinical signs of CSPH as described by either one of the points below. Each trial patient must have a gastroscopy during the screening period or within 6 months prior to screening. (i) documented endoscopic proof of oesophageal varices and / or gastric varices at screening or within 6 months prior to screening (ii) documented endoscopic-treated oesophageal varices as preventative treatment
4. CSPH defined as baseline HVPG ≥ 10 mmHg (measured at Visit 1c), based on a local interpretation of the pressure tracing
5. Diagnosis of compensated cirrhosis due to HCV, HBV, or NASH with or without T2DM. Diagnosis of cirrhosis must be based on histology (historical data is acceptable) or on clinical evidence of cirrhosis (e.g. platelet count < 150 x 109/L [150 x 103/μL], nodular liver surface on imaging or splenomegaly etc.) Diagnosis of NASH based on either i. Current or historic histological diagnosis of NASH OR steatosis OR ii. Clinical diagnosis of NASH based on historic or current imaging diagnosis of fatty liver (Fibroscan, US, MRI, CT) AND at least 2 current or historic comorbidities of the metabolic syndrome (overweight/obesity, T2DM, hypertension, hyperlipidemia)
6. Willing and able to undergo HVPG measurements per protocol (based on Investigator judgement)
7. If receiving statins must be on a stable dose for at least 3 months prior to screening, with no planned dose change throughout the trial
8. If receiving treatment with NSBBs or carvedilol must be on a stable dose for at least 1 month prior to screening, with no planned dose change throughout the trial
9. Further inclusion criteria apply.

Exclusion criteria 9

1. Previous clinically significant decompensation events (e.g. ascites [more than perihepatic ascites], VH and / or overt / apparent HE)
2. History of other forms of chronic liver disease (e.g. alcohol-related liver disease (ARLD), autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilson’s disease, haemachromatosis, alpha-1 antitrypsin [A1At] deficiency)
3. Patients without adequate treatment for HBV, HCV or NASH as per local guidance (e.g. antiviral therapy for chronic HBV or HCV infection or lifestyle modification in NASH) - if received curative anti-viral therapy for HCV, no sustained virological response (SVR) or SVR sustained for less than 2 years prior to screening or if HCV RNA detectable - If receiving anti-viral therapy for HBV, less than 6 months on a stable dose prior to screening, with planned dose change during the trial or HBV DNA detectable - Weight change ≥ 5% within 6 months prior screening
4. Must take, or wishes to continue the intake of, restricted concomitant therapy or any concomitant therapy considered likely (based on Investigator judgement) to interfere with the safe conduct of the trial
5. SBP < 100 mmHg and DBP < 70 mmHg at screening
6. Model of End-stage Liver Disease (MELD) score of > 15 at screening, calculated by the central laboratory
7. Hepatic impairment defined as a Child-Turcotte-Pugh score ≥ B8 at screening, calculated by the site, using central laboratory results
8. ALT or AST > 5 times upper limit of normal (ULN) at screening, measured by the central laboratory
9. Further exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the percentage change in HVPG from baseline (measured in mmHg) after 8 weeks of treatment.

Secondary endpoints 4

1. Occurrence of a response, which is defined as > 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment
2. Occurrence of one or more decompensation events (i.e. ascites, VH, and / or overt HE) during the 8-week treatment period
3. Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 8-week treatment period
4. Occurrence of discontinuation due to hypotension or syncope during the 8-week treatment period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Third parties 1

Boehringer Ingelheim Espana S.A.

Sponsor organisation

Boehringer Ingelheim Espana S.A.

Address

Carrer Prat De La Riba 50

City

Sant Cugat Del Valles

Postcode

08174

Country

Spain

Boehringer Ingelheim RCV GmbH & Co. KG

Sponsor organisation

Boehringer Ingelheim RCV GmbH & Co. KG

Address

Dr.-Boehringer-Gasse 5-11, Meidling Meidling

City

Vienna

Postcode

1120

Country

Austria

Sponsor responsibilities

Article 77 compliance

Boehringer Ingelheim International GmbH

Contact point sponsor

Boehringer Ingelheim International GmbH

Article 77 implementation

Boehringer Ingelheim International GmbH

Locations

9 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications