Safety and Tolerability of Yaq-001 in Patients With Cirrhosis

NCT ID: NCT03202498

Last Updated: 2020-08-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-28
• Study Completion Date: 2020-03-26

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.

Detailed Description

First-in-human clinical investigation with Yaq-001. This is a multicentre, randomized, double blinded, placebo controlled trial to intended to evaluate safety and tolerability of oral administration of Yaq-001 therapy in two dosing cohorts.

56 cirrhotic patients with diuretic-responsive ascites will be enrolled. Patients will be randomized to two dosing cohorts.

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 patients will be dosed daily with Yaq-001 (or an equivalent quantity of placebo) for 12 weeks. Assessments of DSMB will take place after 4 and 12 weeks. Investigational centres specialized in the management of patients with liver cirrhosis will participate in the study.

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.

The total study duration is estimated to be approximately 6 months from screening of first patient until study completion of the last patient.

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 634579.

Conditions

Liver Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DEVICE_FEASIBILITY
• Blinding Strategy: QUADRUPLE

Study Groups

Cohort 1 (4g Yaq-001)

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

Group Type: EXPERIMENTAL

4g Yaq-001

Intervention Type: 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 Placebo)

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

Group Type: PLACEBO_COMPARATOR

4g Placebo

Intervention Type: 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 2 (8g Yaq-001)

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

Group Type: EXPERIMENTAL

8g Yaq-001

Intervention Type: 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 Placebo)

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

Group Type: PLACEBO_COMPARATOR

8g Placebo

Intervention Type: 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.

Interventions

4g Yaq-001

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.

Intervention Type: DEVICE

4g Placebo

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.

Intervention Type: OTHER

8g Yaq-001

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.

Intervention Type: DEVICE

8g Placebo

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Male and female patients

2. Age ≥ 18 years at screening

3. Clinical diagnosis of cirrhosis for any cause. Liver biopsy is not required

4. Cirrhotic patients with diuretic-responsive ascites and Child-Pugh score = 7-11 inclusive

5. Abstinence from alcohol for at least 4 weeks prior to screening

Exclusion Criteria

1. Refusal or inability (lack of capacity) to give informed consent

2. Prohibited medication within 4 weeks before the start of the study treatment: all oral antibiotics, immunosuppressants, long acting benzodiazepines or barbiturates and antiviral medication

3. Change in dose of proton pump inhibitor therapy within 4 weeks before the start of the study treatment

4. Patients with once daily medications in which orocaecal transit time is greater than 10 hours

5. Patients requiring medication in which the dosing schedule is three times per day or greater

6. Antiviral therapy for hepatitis C within 3 months prior to screening

7. Hospital admission for liver-related indication for at least 4 weeks (except paracentesis)

8. BMI > 35 or BMI < 18

9. Clostridium Difficile diarrhoea within 4 weeks before the start of the study treatment

10. Uncontrolled infection (chronic viral hepatitis is not an exclusion criterion)

11. Human immunodeficiency virus

12. Presence of a transjugular intrahepatic portosystemic shunt (TIPSS)

13. Participation in any clinical study of an investigational medicinal product within 30 days of five half-lives of the investigational product, whichever is longer

14. 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.

15. 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.

16. Women of child bearing potential. Only postmenopausal women or with surgical sterilization will be included.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: collaborator

University of Brighton

OTHER

Sponsor Role: collaborator

Institut d'Investigacions Biomèdiques August Pi i Sunyer

OTHER

Sponsor Role: collaborator

Azienda Ospedaliera di Padova

OTHER

Sponsor Role: collaborator

Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role: collaborator

IRCCS Azienda Ospedaliero-Universitaria di Bologna

OTHER

Sponsor Role: collaborator

University of Lisbon

OTHER

Sponsor Role: collaborator

Servicio Madrileño de Salud, Madrid, Spain

OTHER

Sponsor Role: collaborator

University of Bern

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

A2F Associates Limited

OTHER

Sponsor Role: collaborator

Alpha Bioresearch S.L.

OTHER

Sponsor Role: collaborator

Yaqrit Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rajiv Jalan

Role: STUDY_CHAIR

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

Jane Macnaughtan

Role: STUDY_DIRECTOR

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

Locations

Hospital Beaujon, Hepatology and Liver Intensive Care,

Clichy, , France

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

Bologna, , Italy

Azienda Ospedaliera di Padova, Hepatic Emergencies Unit

Padua, , Italy

University Hospital of Santa Maria

Lisbon, , Portugal

Hospital Vall d'Hebron, Liver Unit

Barcelona, , Spain

Hospital Clinic of Barcelona , Liver Unit,

Barcelona, , Spain

Hospital Ramon y Cajal, Department of Gastroenterology and Hepatology

Madrid, , Spain

Inselspital Universitaet Bern, Department for Visceral Surgery and Medicine,

Bern, , Switzerland

Royal Free Hospital, Institute of Liver and Digestive Disease

London, , United Kingdom

Countries

France; Italy; Portugal; Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38621924 (View on PubMed)

Other Identifiers

Yaq001-S-001

Identifier Type: -

Identifier Source: org_study_id