Safety and efficacy of a human albumin solution with restored structural profile in patients with decompensated cirrhosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23], Diseases [C] - Digestive System Diseases [C06]

Trial duration

1 Sep 2025 → ongoing

Decision date (initial)

2024-10-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministero della Salute-PNRR:M6/C2_CALL 2023 Full Proposal-PNRR-MCNT2-2023-12377463

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary aim is to assess the impact on effective albumin concentration and the safety of the administration of the reHA solution, as compared to the standard commercial HA solution in patients with decompensated cirrhosis having the indication to long-term albumin treatment

Secondary objectives 1

1. The secondary aims are to assess the impact of the reHA solution on several clinical outcomes and surrogate markers of efficacy related to pathophysiological drivers of decompensated cirrhosis

Conditions and MedDRA coding

decompensated cirrhosis

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Diagnosis of liver cirrhosis of any etiology (based on clinical, laboratory, endoscopic and ultrasonographic features); • Patients with grade 2 and 3 ascites according to the criteria of the International Club of Ascites [88] and patients with grade 1 receiving diuretic treatment (at least 200 mg/die of an antialdosteronic drug ± furosemide 25 mg/die); • Patients of both sexes aged between 18 and 85 years; • Written and autonomous informed consent.

Exclusion criteria 1

1. • HA infusion in the prior 2 weeks except for paracentesis, spontaneous bacterial peritonitis (SBP) and acute kidney injury-hepatorenal syndrome (AKI-HRS); • Ongoing acute complications of cirrhosis; • Active malignancy except for hepatocellular carcinoma within Milan criteria; • Previous organ transplantation; • Trans jugular intrahepatic portosystemic shunt (TIPS) or Budd-Chiari syndrome; • Antiviral treatment for viral hepatitis started in the last 6 months; • Ongoing alcohol consumption with >21 alcohol U/week or an expected low adherence to protocol; • Chronic organic renal failure stage IV and V; • Chronic heart failure NYHA class III or IV; • Chronic obstructive pulmonary disease GOLD III or IV; • Life expectancy <6 months due to extrahepatic diseases; • Severe psychiatric disorders; • Known or suspected hypersensitivity to HA; • Pregnancy and breast-feeding; • Patients enrolled in other interventional clinical study for the treatment of complication of cirrhosis; • Use of experimental drugs for the last 2 months prior the inclusion in the present study • Hypersensitivity to albumin preparations or to any of the excipients; • Hypersensitivity to Glutathione or any component of the Glutathione solution; • Females of child-bearing potential are excluded unless they meet one of the following criteria: - Post-menopausal defined as no menses for 12 months without an alternative medical cause [89]. If post-menopausal for less than 12 months, a negative pregnancy test is required; - Surgical sterilization for more than one month duration and a negative pregnancy test (permanent sterilization methods include: hysterectomy, bilateral salpingectomy and bilateral oophorectomy) [89]; - Intrauterine device in combination with a secondary barrier (e.g. diaphragm, condom or spermicide) and a negative pregnancy test.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoints of the study will be: - Effective albumin concentration at 1, 3 and 6 months from randomization - Safety of the reHA solution during the 6-month treatment assessed by collecting vital signs, lab parameters and any adverse event, namely: • Percentage of subjects with at least 1 adverse event (AE) or serious adverse event (SAE); • Percentage of subjects with at least 1 Adverse Drug Reaction (ADR); •Total number of AE, SAE and ADR; [truncated text, see protocol for details]

Secondary endpoints 1

1. Signals of efficacy will be searched by comparing the following parameters at 1, 3 and 6 months from randomization: Organ function: Liver function: grade of ascites (International Club of Ascites criteria), grade of HE (West Haven classification and Animal Naming Test), bilirubin and albumin serum levels; Renal function: BUN, serum creatinine, electrolytes, eGFR estimated by the CKD-EPI equation;[truncated text, see protocol for details]

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Sponsor organisation

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Address

Via Pietro Albertoni 15

City

Bologna

Postcode

40138

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Contact name

Paolo Caraceni

Public contact point

Organisation

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Contact name

Barbara Lotito

Third parties 1

Locations

1 EU/EEA country · 4 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

Documents 12 files

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

Application history

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