Study in Patients With Decompensated Liver Cirrhosis

Liver Cirrhosis Clinical Trial

— OPAL  

Official title:

A Multicentre, Observational Study in Patients With Liver Cirrhosis Who Have Hepatic Decompensation (OPAL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06380335
• Other study ID #: RTX001-01S
• Status: Recruiting
• Start date: October 10, 2023
• Est. completion date: November 3, 2026

Study information

• Verified date: April 2024
• Source: Resolution Therapeutics Limited
• Contact: Victor Dillard
• Phone: +442037811105
• Email: clinical.enquiries[@]resolution-tx.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

OPAL is a multicenter observational study, following the natural disease trajectory of participants who have permanent damage to their liver caused by scarring, sometimes also referred to as liver cirrhosis. These participants will also have recently had an acute worsening of their liver disease, which is also known as a hepatic decompensating event, which has resulted in them being admitted to hospital or required them to seek medical attention as an outpatient.

Description:

This multicenter, observational natural history study is designed to follow the disease trajectory of adults with cirrhosis of the liver who have a qualifying hepatic decompensation event. The primary objective of the study is to obtain real world data to understand the clinical course of cirrhotic patients following a decompensation event in order to generate data to provide context for the safety and efficacy evaluation of future interventional treatments. Observed data will be collected from the visits and assessments conducted as part of the routine standard of care (SOC) follow-up of these patients. In addition, given the variability in SOC and timing of follow-up visits across institutions, if study required assessments do not coincide with a routine SOC visit at the institution, blood draws and other study-specific assessments will be collected at defined time points for the study analysis. All participants who meet the eligibility criteria and stabilize following a hepatic decompensation event will have their clinical course followed for up to 96 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: November 3, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Individuals eligible to participate in this study must meet the following criteria:

Inclusion Criteria:

1. Male or female age =18-75 years.

2. Patient is willing and able to provide informed consent to participate in the study.

3. Patient confirms willingness/ability to comply with all study procedures.

4. Has a diagnosis of liver cirrhosis determined by a physician based on at least one of

the following:

1. clinical and radiological features that correlate with a diagnosis of cirrhosis;

2. transient elastography (TE) (FibroscanTM) >15kPa;

3. previous liver biopsy confirming histological features of cirrhosis.

5. For eligibility at Screen Part 2 - Aetiology of liver disease of pure metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic and alcohol related/associated liver disease (MetALD), or alcohol-related liver disease (ALD) providing no active alcohol misuse (see Exclusion criterion 11) =3 months prior to screening, or hepatitis C virus sustained virologic response (HCV SVR) with ongoing cirrhosis.

6. Meets one of the following criteria:

1. has been hospitalised as an in-patient for the first time for a major hepatic decompensation event (qualifying event) defined as either ascites, hepatic encephalopathy (HE) or variceal bleed, OR

2. has intractable hepatic decompensation, defined as continuing diuretic resistant ascites requiring frequent paracentesis, or ongoing hepatic encephalopathy despite medical therapy, or medium to large gastrointestinal varices treated with repeated banding, treated only in an out-patient setting. NOTE: the study will only screen up to a maximum of 10 patients with intractable hepatic decompensation, limited to a maximum of three patients per site.

7. MELD 3.0 score of 12-20 taken within 2 weeks of qualifying event.

8. Has stabilised post-hepatic decompensation event, as defined by two MELD assessments (within 1 point of each) other taken within 2 weeks, or physician assessed as stable. with the ability to safely cell mobilise with GCSF, apherese and received RTX001 treat in the interventional Phase 1/2 study.

Exclusion Criteria:

1. Liver cirrhosis due to:

1. any viral hepatitis with the exception of HCV SVR, or

2. autoimmune and cholestatic aetiologies including, but not limited to, primary biliary cholangitis and primary sclerosing cholangitis.

2. Acute liver disease in the absence of underlying liver cirrhosis, including, but not limited to, drug induced liver injury.

3. Any prior hospitalisation for or resulting from a decompensation event (unless in the intractable hepatic decompensation subgroup).

4. Any current organ failure requiring more than out-patient non-invasive supportive care, and not associated with the patient's qualifying hepatic decompensation event.

5. Known splenomegaly =16cm.

6. Thrombocytopenia <50,000 mm3.

7. Sepsis (with positive microbial cultures) or as defined by the PI, within 12 weeks of consent.

8. Presence or suspicion of any of the following co-morbidities:

1. history of liver transplantation or other organ transplant;

2. acute on chronic liver failure (ACLF);

3. spontaneous bacterial peritonitis;

4. human immunodeficiency virus;

5. pulmonary embolism;

6. refractory ascites, with exception of the small group of patients with continuing diuretic resistant ascites requiring frequent paracentesis (see Inclusion criteria 6b);

7. hepatocellular carcinoma, or active malignant disease within the last 5 years, (excluding non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, benign polyps etc.);

8. co-hepatic morbidities e.g., hepatic hydrothorax (refractory to medical management), portal vein thrombosis;

9. chronic renal impairment (on dialysis) or unresolved acute kidney injury;

10. acute or chronic heart failure;

11. porto-pulmonary hypertension;

12. severe chronic lung disease e.g., chronic obstructive pulmonary disease or interstitial lung disease where the forced expiratory volume (FEV1) is less than 50% and/or FEV1/forced vital capacity is less than 60%;

13. hepatopulmonary syndrome;

14. history or current treatment with chronic albumin treatment;

15. significant untreated/unstable psychiatric disease.

9. Current or planned use of immunosuppressive medication, with the exception of low doses up to 10 mg/day prednisone or equivalent, or inhaled steroids to manage an asthma, which are permitted.

9. Current or planned use of immunosuppressive medication, with the exception of low doses up to 10 mg/day prednisone or equivalent, or inhaled steroids to manage an asthma, which are permitted.

10. Any other intercurrent illness that is either life-threatening or of clinical significance such that it might limit compliance with study procedures, in the Investigator's opinion.

11. Current/recent alcohol misuse = 3 months prior to screening, defined as alcohol intake greater than 3 units/day for females and 4 units/day for males, or binge drinking (>14 units/day) as determined by the Investigator, or intake of non-medically supervised drugs of abuse that is judged (by the Investigator) to be a high risk to the patients acute health or which makes the patient likely to be non-compliant with follow-up. N.B. One alcohol unit is equivalent to14 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

12. Are currently participating in an investigational interventional study. Note:

concurrent participation in another non-interventional study is permitted.

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis

Locations

Country	Name	City	State
United Kingdom	Bristol Royal Infirmary	Bristol
United Kingdom	Royal Infirmary Edinburgh	Edinburgh
United Kingdom	Royal Liverpool Hospital	Liverpool
United Kingdom	King's College Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	St Mary's Hospital	London
United Kingdom	Nottingham University Hospital	Nottingham
United Kingdom	Sunderland Royal Hospital	Sunderland

Sponsors (1)

Lead Sponsor	Collaborator
Resolution Therapeutics Limited

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Explore clinical and laboratory parameters.	Common clinical laboratory parameters to assess end stage liver disease.	Screening up to 96 weeks
Other	Evaluate the effect of disease progression on biomarkers of inflammatory activity	Additional non-invasive biomarkers of liver fibrogenesis or fibrolysis and/or molecules reflecting hepatic function.	Screening up to 96 weeks
Primary	Examine the characteristics of patients admitted to hospital with hepatic decompensation.	Demographics	Baseline and up to 96 weeks
Primary	Examine the characteristics of patients admitted to hospital with hepatic decompensation.	Aetiology of liver disease	Baseline and up to 96 weeks
Primary	Examine the characteristics of patients admitted to hospital with hepatic decompensation.	Disease co-morbidities	Baseline and up to 96 weeks
Primary	Examine the characteristics of patients admitted to hospital with hepatic decompensation.	Alcohol use	Baseline, and up to 96 weeks
Primary	Examine the characteristics of patients admitted to hospital with hepatic decompensation.	Changes in Model for End-Stage Liver Disease (MELD) score	Baseline, and up to 96 weeks
Primary	Examine the characteristics of patients admitted to hospital with hepatic decompensation.	Safety laboratory (biochemistry and haematology) parameters	Baseline, and up to 96 weeks
Secondary	Follow the natural history of patients admitted to hospital with hepatic decompensation.	Death or liver transplantation	Screening up to 96 weeks
Secondary	Follow the natural history of patients admitted to hospital with hepatic decompensation.	Major hepatic decompensation events	Screening up to 96 weeks
Secondary	Follow the natural history of patients admitted to hospital with hepatic decompensation.	Hospitalisations or intensive care unit (ICU) admissions	Screening up to 96 weeks
Secondary	Follow the natural history of patients admitted to hospital with hepatic decompensation.	Changes in Model for End-Stage Liver Disease (MELD) score	Screening up to 96 weeks
Secondary	Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.	Demographics	Screening up to 96 weeks
Secondary	Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.	Safety laboratory (biochemistry and haematology) parameters	Screening up to 96 weeks
Secondary	Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.	Disease co morbidities	Screening up to 96 weeks
Secondary	Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.	Alcohol use	Screening up to 96 weeks
Secondary	Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.	Changes in MELD score	Screening up to 96 weeks
Secondary	Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.	Death or liver transplantation	Screening up to 96 weeks
Secondary	Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.	Further hepatic decompensation events	Screening up to 96 weeks