A study to test whether BI 685509 helps people with liver cirrhosis and high blood pressure in the portal vein (main vessel going to the liver) who had bleeding in the esophagus or fluid accumulation in the belly

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

16 Feb 2024 → 30 May 2024

Decision date (initial)

2023-11-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-506083-13-00

WHO UTN

U1111-1293-6879

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

The trial will investigate the safety and tolerability of BI 685509 in patients with CSPH in decompensated cirrhosis due to non-cholestatic liver diseases on top of standard of care. The primary objective is to estimate the percentage change in HVPG from baseline measured after 8 weeks in comparison to placebo.

Conditions and MedDRA coding

clinically significant portal hypertension (CSPH) in decompensated cirrhosis due to non-cholestatic liver disease

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 10

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. Diagnosis of cirrhosis due to non-cholestatic liver disease (including HCV, HBV, NASH, alcohol-related liver disease, autoimmune hepatitis, Wilson’s disease, haemachromatosis, alpha-1 antitrypsin [A1At] deficiency)
4. One previous clinically significant decompensation event with clinical resolution at least 4 weeks prior start of screening (visit 1a): a. First variceal haemorrhage b. First episode of clinically significant ascites (requiring intervention in lifestyle [fluid and salt restriction] or medical treatment)
5. Willing and able to undergo HVPG measurements per protocol (based on Investigator judgement)
6. If receiving statins must be on a stable dose for at least 3 months prior to screening (Visit 1b), with no planned dose change throughout the trial
7. If receiving treatment with NSBBs or carvedilol must be on a stable dose for at least 1 month prior to screening (Visit 1b), with no planned dose change throughout the trial
8. For patient with alcohol-related cirrhosis, abstinence from significant alcohol misuse / abuse for a minimum of 2 months prior to screening (Visit 1a), and the ability to abstain from alcohol throughout the trial (both evaluated based on Investigator judgement)
9. WOCBP must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly from the randomisation visit (Visit 2) until 7 days after the last treatment in this trial. The patient must agree to periodic pregnancy testing during participation in the trial
10. Men able to father a child and who have a female sexual partner of CBP, must use a condom with or without spermicide, or adopt complete sexual abstinence, or be vasectomised (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate), from the randomisation visit (Visit 2) until 7 days after the last treatment in this trial

Exclusion criteria 13

1. History of cholestatic chronic liver disease (e.g. primary biliary sclerosis, primary sclerosing cholangitis)
2. Trial participants 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)
3. If received curative anti-viral therapy for HCV, SVR sustained for less than 1 years prior to screening
4. 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
5. Weight change ≥5% within 6 months prior screening in patients with NASH
6. 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
7. SBP <100 mmHg or DBP <70 mmHg at screening (Visit 1a)
8. Hepatic impairment defined as a Child-Turcotte-Pugh score ≥8 at screening
9. Model of End-stage Liver Disease (MELD) score of >15 at screening (Visit 1a), calculated by the central laboratory
10. ALT or AST >5 times upper limit of normal (ULN) at screening (Visit 1a), measured by the central laboratory
11. eGFR (CKD-EPI formula) < 20 mL/min/1.73 m2 at screening (Visit 1a), measured by the central laboratory
12. Platelet count <50x10^9/L
13. Further exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 further 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 3

Placebo 3

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, Sant Cugat Del Valles Sant Cugat Del Valles

City

Barcelona

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

1121

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

5 EU/EEA countries · 10 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 6 files

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

Application history

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