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Safety and Tolerability of Yaq-001 in Patients With Cirrhosis

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ClinicalTrials.gov Identifier: NCT03202498
Recruitment Status : Not yet recruiting
First Posted : June 28, 2017
Last Update Posted : June 29, 2018
Sponsor:
Collaborators:
University College, London
University of Brighton
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Azienda Ospedaliera di Padova
Hospital Universitari Vall d'Hebron Research Institute
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
University of Lisbon
Servicio Madrileño de Salud, Madrid, Spain
University of Bern
Assistance Publique - Hôpitaux de Paris
ALPHABIORESEARCH S.L.
A2F ASSOCIATES LIMITED
Information provided by (Responsible Party):
Yaqrit Ltd

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.


Condition or disease Intervention/treatment Phase
Liver Cirrhosis Device: 4g Yaq-001 Other: 4g Placebo Device: 8g Yaq-001 Other: 8g Placebo Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Placebo
Primary Purpose: Device Feasibility
Official Title: Safety and Tolerability of Yaq-001 in Patients With Cirrhosis ("CARBALIVE-SAFETY")
Estimated Study Start Date : October 1, 2018
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis

Arm Intervention/treatment
Experimental: Cohort 1 (4g Yaq-001)
Standard medical treatment + Yaq-001 (4 g/ day)
Device: 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.

Placebo Comparator: Cohort 1 (4g Placebo)
Standard medical treatment + placebo-control (placebo for 4 g of Yaq-001/ day)
Other: 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.

Experimental: Cohort 2 (8g Yaq-001)
Standard medical treatment + Yaq-001 (8 g/ day)
Device: 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.

Placebo Comparator: Cohort 2 (8g Placebo)
Standard medical treatment + placebo-control (placebo for 8 g of Yaq-001/ day)
Other: 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.




Primary Outcome Measures :
  1. Assessment of reported and observed Serious Adverse Events [ Time Frame: Day 1 ]
    The percentage of patients experiencing SAEs will be tabulated by arm.

  2. Assessment of treatment-related Serious Adverse Events [ Time Frame: Day 1 ]
    The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  3. Assessment of withdrawals due to Adverse Events [ Time Frame: Day 1 ]
    The percentage of patients who withdraw due to an AE will be tabulated by arm.

  4. Assessment of reported and observed Serious Adverse Events [ Time Frame: Week 1 ]
    The percentage of patients experiencing SAEs will be tabulated by arm.

  5. Assessment of treatment-related Serious Adverse Events [ Time Frame: Week 1 ]
    The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  6. Assessment of withdrawals due to Adverse Events [ Time Frame: Week 1 ]
    The percentage of patients who withdraw due to an AE will be tabulated by arm.

  7. Assessment of reported and observed Serious Adverse Events [ Time Frame: Week 4 ]
    The percentage of patients experiencing SAEs will be tabulated by arm.

  8. Assessment of treatment-related Serious Adverse Events [ Time Frame: Week 4 ]
    The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  9. Assessment of withdrawals due to Adverse Events [ Time Frame: Week 4 ]
    The percentage of patients who withdraw due to an AE will be tabulated by arm.

  10. Assessment of reported and observed Serious Adverse Events [ Time Frame: Week 8 ]
    The percentage of patients experiencing SAEs will be tabulated by arm.

  11. Assessment of treatment-related Serious Adverse Events [ Time Frame: Week 8 ]
    The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  12. Assessment of withdrawals due to Adverse Events [ Time Frame: Week 8 ]
    The percentage of patients who withdraw due to an AE will be tabulated by arm

  13. Assessment of reported and observed Adverse Events [ Time Frame: Week 12 ]
    The percentage of patients experiencing SAEs will be tabulated by arm.

  14. Assessment of treatment-related Serious Adverse Events [ Time Frame: Week 12 ]
    The percentage of patients experiencing device-related SAEs will be tabulated by arm.

  15. Assessment of withdrawals due to Adverse Events [ Time Frame: Week 12 ]
    The percentage of patients who withdraw due to an AE will be tabulated by arm.


Secondary Outcome Measures :
  1. Assessment of changes in blood endotoxin activity [ Time Frame: The EAA will be performed at randomization, 1-week, 4-week, 8-week and 12-week visits. ]
    The changes from baseline in blood endotoxin activity, measured by the EAA, will be used as device-related performance indicator.

  2. Assessment of changes in organ function as per the CHILD-PUGH score [ Time Frame: CHILD-PUGH scores will be calculated at screening, randomization, 1-week, 4-week, 8-week and 12-week visits. ]
    Changes from baseline in kidney, liver, brain, intestinal and immune functions will be assessed by means of the CHILD-PUGH score.

  3. Assessment of changes in organ function as per the MELD score [ Time Frame: MELD scores will be calculated at screening, randomization, 1-week, 4-week, 8-week and 12-week visits. ]
    Changes from baseline in kidney, liver, brain, intestinal and immune functions will be assessed by means of the MELD score.

  4. Assessment of changes in nutritional status [ Time Frame: Global assessment will be performed at randomization, 1-week, 4-week, 8-week and 12-week visits. ]
    Changes from baseline in nutritional status be assessed by means of the global assessment score (RFH-GA);



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03202498


Contacts
Contact: Eugenia Vellve +34933233472 eugenia.vellve@alphabioresearch.com
Contact: Maria J. Estefano +34933233472 mjose.estefano@alphabioresearch.com

Locations
France
Hospital Beaujon, Hepatology and Liver Intensive Care, Not yet recruiting
Clichy, France, 82110
Contact: Francois Durand    + 33 01 40 87 50 00      
Italy
Policlinico S.Orsola Malpighi, Department of Medical and Surgical Sciences Not yet recruiting
Bologna, Italy, 40138
Contact: Paolo Caraceni    + 39 051 636 2 919      
Azienda Ospedaliera di Padova, Hepatic Emergencies Unit Not yet recruiting
Padova, Italy, 35128
Contact: Paolo Angeli    +39 049 821 2 004      
Portugal
University Hospital of Santa Maria Not yet recruiting
Lisbon, Portugal, 1649-035
Contact: Helena Cortez-Pinto    +351 21 780 5000      
Spain
Hospital Vall d'Hebron, Liver Unit Not yet recruiting
Barcelona, Spain, 08035
Contact: Victor Vargas    +34 93 489 30 00      
Hospital Clinic of Barcelona , Liver Unit, Not yet recruiting
Barcelona, Spain, 08036
Contact: Pere Gines    +34 93 227 17 13      
Hospital Ramon y Cajal, Department of Gastroenterology and Hepatology Not yet recruiting
Madrid, Spain, 28034
Contact: Agustin Albillos    +34 91 336 85 92      
Switzerland
Inselspital Universitaet Bern, Department for Visceral Surgery and Medicine, Not yet recruiting
Bern, Switzerland, 3010
Contact: Reiner Wiest    +41 31 632 0291      
United Kingdom
Royal Free Hospital, Institute of Liver and Digestive Disease Not yet recruiting
London, United Kingdom, NW3 2PF
Contact: Raj Mookerjee    +44 207 794 0500      
Sponsors and Collaborators
Yaqrit Ltd
University College, London
University of Brighton
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Azienda Ospedaliera di Padova
Hospital Universitari Vall d'Hebron Research Institute
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
University of Lisbon
Servicio Madrileño de Salud, Madrid, Spain
University of Bern
Assistance Publique - Hôpitaux de Paris
ALPHABIORESEARCH S.L.
A2F ASSOCIATES LIMITED
Investigators
Study Chair: Rajiv Jalan Head, Liver Failure Group ILDH, Division of Medicine UCL Medical School Royal Free Campus Rowland Hill Street London NW32PF
Study Director: Jane Macnaughtan Consultant, Liver Failure Group, ILDH, Division of Medicine UCL Medical School Royal Free Campus Rowland Hill Street London NW32PF

Responsible Party: Yaqrit Ltd
ClinicalTrials.gov Identifier: NCT03202498     History of Changes
Other Study ID Numbers: Yaq001-S-001
First Posted: June 28, 2017    Key Record Dates
Last Update Posted: June 29, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yaqrit Ltd:
Cirrhosis, Liver
Fibrosis, Liver
Hepatic Cirrhosis
Liver Fibrosis

Additional relevant MeSH terms:
Fibrosis
Liver Cirrhosis
Pathologic Processes
Liver Diseases
Digestive System Diseases