Safety and Tolerability of Yaq-001 in Patients With Cirrhosis

NCT03202498 | Terminated

• 1 other identifier: Yaq001-S-001
• Study Type: interventional
• Target: 31
• Locations: 6 countries
• Sites: 9

Brief Summary

In patients with cirrhosis (scarring of the liver), bacterial fragments leak from the gut into the blood and cause harm. This study looks into a new way to lower the leakage of bacterial fragments into the blood. Yaq-001 is a new type of carbon that in previous laboratory studies has been shown to have the ability to bind these bacterial fragments and so confine them to the gut. The purpose of this clinical trial is to test the product Yaq-001 for the first time in patients with cirrhosis. This trial will assess if the treatment with Yaq-001 is safe, is well tolerated, and if it helps improve the overall health status of the cirrhotic patients. Candidate patients must be at least 18 years old and have a clinical diagnosis of cirrhosis for any cause. Only postmenopausal women or with surgical sterilisation are eligible. Additional inclusion and exclusion criteria of medical nature will be determined with the investigator at the screening visit, by means of standard care routines plus an additional test to assess the bowel transit time. Eligible patients will be randomly grouped to receive standard care treatment plus Yaq-001, or standard treatment plus placebo (non-active treatment). The use of placebo is necessary to better understand how safe and tolerable Yaq-001 really is. The treatment lasts for 12 weeks. During treatment, the patient will be visited by a study doctor 5 times. At all the visits the patients will undergo a routine physical examination, electrocardiogram, collection of blood and urine samples. On three occasions the patients will be asked to provide additional samples of blood, urine and stool for analysis outside the hospital. 56 patients from 9 hospitals in UK, France, Italy, Portugal, Spain and Switzerland will participate in this study.

Conditions

Liver Cirrhosis

Keywords

Cirrhosis, Liver; Fibrosis, Liver; Hepatic Cirrhosis; Liver Fibrosis

Outcome Measures

Primary Outcomes (15)

• Assessment of reported and observed Serious Adverse Events

  The percentage of patients experiencing SAEs will be tabulated by arm.

  Day 1

• Assessment of treatment-related Serious Adverse Events

  The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  Day 1

• Assessment of withdrawals due to Adverse Events

  The percentage of patients who withdraw due to an AE will be tabulated by arm.

  Day 1

• Assessment of reported and observed Serious Adverse Events

  The percentage of patients experiencing SAEs will be tabulated by arm.

  Week 1

• Assessment of treatment-related Serious Adverse Events

  The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  Week 1

• Assessment of withdrawals due to Adverse Events

  The percentage of patients who withdraw due to an AE will be tabulated by arm.

  Week 1

• Assessment of reported and observed Serious Adverse Events

  The percentage of patients experiencing SAEs will be tabulated by arm.

  Week 4

• Assessment of treatment-related Serious Adverse Events

  The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  Week 4

• Assessment of withdrawals due to Adverse Events

  The percentage of patients who withdraw due to an AE will be tabulated by arm.

  Week 4

• Assessment of reported and observed Serious Adverse Events

  The percentage of patients experiencing SAEs will be tabulated by arm.

  Week 8

• Assessment of treatment-related Serious Adverse Events

  The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  Week 8

• Assessment of withdrawals due to Adverse Events

  The percentage of patients who withdraw due to an AE will be tabulated by arm

  Week 8

• Assessment of reported and observed Adverse Events

  The percentage of patients experiencing SAEs will be tabulated by arm.

  Week 12

• Assessment of treatment-related Serious Adverse Events

  The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  Week 12

• Assessment of withdrawals due to Adverse Events

  The percentage of patients who withdraw due to an AE will be tabulated by arm.

  Week 12

Secondary Outcomes (4)

• Assessment of changes in blood endotoxin activity

  The EAA will be performed at randomization, 1-week, 4-week, 8-week and 12-week visits.

• Assessment of changes in organ function as per the CHILD-PUGH score

  CHILD-PUGH scores will be calculated at screening, randomization, 1-week, 4-week, 8-week and 12-week visits.

• Assessment of changes in organ function as per the MELD score

  MELD scores will be calculated at screening, randomization, 1-week, 4-week, 8-week and 12-week visits.

• Assessment of changes in nutritional status

  Global assessment will be performed at randomization, 1-week, 4-week, 8-week and 12-week visits.

Study Arms (4)

Cohort 1 (4g Yaq-001)

EXPERIMENTAL

Standard medical treatment + Yaq-001 (4 g/ day)

Device: 4g Yaq-001

Cohort 1 (4g Placebo)

PLACEBO COMPARATOR

Standard medical treatment + placebo-control (placebo for 4 g of Yaq-001/ day)

Other: 4g Placebo

Cohort 2 (8g Yaq-001)

EXPERIMENTAL

Standard medical treatment + Yaq-001 (8 g/ day)

Device: 8g Yaq-001

Cohort 2 (8g Placebo)

PLACEBO COMPARATOR

Standard medical treatment + placebo-control (placebo for 8 g of Yaq-001/ day)

Other: 8g Placebo

Interventions

4g Yaq-001 DEVICE

Study patients will be dosed daily with 4g of product Yaq-001 for a period of 12 weeks. The product will be provided as beads packed in individual sachets intended each for one oral administration. For each patient, the study duration will be up to 17 weeks, including the screening (up to 4 weeks), treatment (12 weeks) and 7-day follow up period.

Cohort 1 (4g Yaq-001)

4g Placebo OTHER

Study patients will be dosed daily with a quantity of placebo equivalent to 4g of product Yaq-001 for a period of 12 weeks. The product will be provided as beads packed in individual sachets intended each for one oral administration. For each patient, the study duration will be up to 17 weeks, including the screening (up to 4 weeks), treatment (12 weeks) and 7-day follow up period.

Cohort 1 (4g Placebo)

8g Yaq-001 DEVICE

Study patients will be dosed daily with 8g of product Yaq-001 for a period of 12 weeks. The product will be provided as beads packed in individual sachets intended each for one oral administration. For each patient, the study duration will be up to 17 weeks, including the screening (up to 4 weeks), treatment (12 weeks) and 7-day follow up period.

Cohort 2 (8g Yaq-001)

8g Placebo OTHER

Study patients will be dosed daily with a quantity of placebo equivalent to 8g of product Yaq-001 for a period of 12 weeks. The product will be provided as beads packed in individual sachets intended each for one oral administration. For each patient, the study duration will be up to 17 weeks, including the screening (up to 4 weeks), treatment (12 weeks) and 7-day follow up period.

Cohort 2 (8g Placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients
• Age ≥ 18 years at screening
• Clinical diagnosis of cirrhosis for any cause. Liver biopsy is not required
• Cirrhotic patients with diuretic-responsive ascites and Child-Pugh score = 7-11 inclusive
• Abstinence from alcohol for at least 4 weeks prior to screening

You may not qualify if:

• Refusal or inability (lack of capacity) to give informed consent
• Prohibited medication within 4 weeks before the start of the study treatment: all oral antibiotics, immunosuppressants, long acting benzodiazepines or barbiturates and antiviral medication
• Change in dose of proton pump inhibitor therapy within 4 weeks before the start of the study treatment
• Patients with once daily medications in which orocaecal transit time is greater than 10 hours
• Patients requiring medication in which the dosing schedule is three times per day or greater
• Antiviral therapy for hepatitis C within 3 months prior to screening
• Hospital admission for liver-related indication for at least 4 weeks (except paracentesis)
• BMI \> 35 or BMI \< 18
• Clostridium Difficile diarrhoea within 4 weeks before the start of the study treatment
• Human immunodeficiency virus
• Presence of a transjugular intrahepatic portosystemic shunt (TIPSS)
• Participation in any clinical study of an investigational medicinal product within 30 days of five half-lives of the investigational product, whichever is longer
• Presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, renal, hepatic, metabolic, haematological, neurological, psychiatric, systemic, ocular, gynaecologic or any acute infection disease or signs of acute illness that, in the opinion of the investigator, might compromise the patient's safe participation in the trial and/or results in a WHO performance status of 2 or more.
• Presence of the history of cancer within the past 5 years with exception of hepatocellular carcinoma within Milan criteria, adequately treated localised basal cell carcinoma of the skin, in situ cervical carcinoma or solid malignancy surgical excised in total without recurrence for five years.
• Women of child bearing potential. Only postmenopausal women or with surgical sterilization will be included.

Sponsors & Collaborators

• Yaqrit Ltd: lead
• University College, London: collaborator
• University of Brighton: collaborator
• Institut d'Investigacions Biomèdiques August Pi i Sunyer: collaborator
• Azienda Ospedaliera di Padova: collaborator
• Hospital Universitari Vall d'Hebron Research Institute: collaborator
• IRCCS Azienda Ospedaliero-Universitaria di Bologna: collaborator
• University of Lisbon: collaborator
• Servicio Madrileño de Salud, Madrid, Spain: collaborator
• University of Bern: collaborator
• Assistance Publique - Hôpitaux de Paris: collaborator
• A2F Associates Limited: collaborator
• Alpha Bioresearch S.L.: collaborator

Study Sites (9)

Hospital Beaujon, Hepatology and Liver Intensive Care,

Clichy, 82110, France

Location

Policlinico S.Orsola Malpighi, Department of Medical and Surgical Sciences

Bologna, 40138, Italy

Location

Azienda Ospedaliera di Padova, Hepatic Emergencies Unit

Padua, 35128, Italy

Location

University Hospital of Santa Maria

Lisbon, 1649-035, Portugal

Location

Hospital Vall d'Hebron, Liver Unit

Barcelona, 08035, Spain

Location

Hospital Clinic of Barcelona , Liver Unit,

Barcelona, 08036, Spain

Location

Hospital Ramon y Cajal, Department of Gastroenterology and Hepatology

Madrid, 28034, Spain

Location

Inselspital Universitaet Bern, Department for Visceral Surgery and Medicine,

Bern, 3010, Switzerland

Location

Royal Free Hospital, Institute of Liver and Digestive Disease

London, NW3 2PF, United Kingdom

Location

Related Publications (1)

• Liu J, MacNaughtan J, Kerbert AJC, Portlock T, Martinez Gonzalez J, Jin Y, Clasen F, Habtesion A, Ji H, Jin Q, Phillips A, De Chiara F, Ingavle G, Jimenez C, Zaccherini G, Husi K, Rodriguez Gandia MA, Cordero P, Soeda J, McConaghy L, Oben J, Church K, Li JV, Wu H, Jalan A, Gines P, Sola E, Eaton S, Morgan C, Kowalski M, Green D, Gander A, Edwards LA, Cox IJ, Cortez-Pinto H, Avery T, Wiest R, Durand F, Caraceni P, Elosua R, Vila J, Pavesi M, Arroyo V, Davies N, Mookerjee RP, Vargas V, Sandeman S, Mehta G, Shoaie S, Marchesi J, Albillos A, Andreola F, Jalan R. Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis. Gut. 2024 Jun 6;73(7):1183-1198. doi: 10.1136/gutjnl-2023-330699.

  PMID: 38621924 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rajiv Jalan

  Head, Liver Failure Group ILDH, Division of Medicine UCL Medical School Royal Free Campus Rowland Hill Street London NW32PF

  STUDY CHAIR

• Jane Macnaughtan

  Consultant, Liver Failure Group, ILDH, Division of Medicine UCL Medical School Royal Free Campus Rowland Hill Street London NW32PF

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohort 1 (1:1 randomization): Standard medical treatment + Yaq-001 (4 g/ day) - n= 14. Standard medical treatment + placebo-control (placebo for 4 g of Yaq-001/ day) - n= 14. Cohort 2 (1:1 randomization): Standard medical treatment + Yaq-001 (8 g/ day) - n= 14. Standard medical treatment + placebo-control (placebo for 8 g of Yaq-001/ day) - n= 14.

Study Record Dates

• First Submitted: April 5, 2017
• First Posted: June 28, 2017
• Study Start: February 28, 2019
• Primary Completion: March 26, 2020
• Study Completion: March 26, 2020
• Last Updated: August 25, 2020

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1); IT (2); FR (1); GB (1); PT (1); ES (3)