Safety and Tolerability of Yaq-001 in Patients With Non-Alcoholic Steatohepatitis

NCT03962608 | Withdrawn

• 1 other identifier: Yaq001-S-002
• Study Type: interventional
• Target: N/A
• Locations: 6 countries
• Sites: 9

Brief Summary

Gut-derived endotoxaemia, microbial imbalance and bacterial translocation play an increasingly recognized role in the progression from non-alcoholic fatty liver disease (NAFLD) to its more advanced state, NASH (non-alcoholic steatohepatitis). Animal model studies confirmed that Yaq-001 reduces liver injury and prevents steatosis in these models which leads to the theoretical potential of Yaq-001 altering the microbiome and gut permeability in patients with NASH. The purpose of this clinical trial is to study the safety and tolerability of Yaq-001 in patients with NASH. Results from this study will lead to the design of future pivotal performance and safety trials for registration purposes. Candidate patients must be between 18-70 years old and have a clinical diagnosis of NASH, determined histologically or phenotypically, as well as meeting other clinical inclusion/exclusion criteria. Eligible patients will be randomly assigned to receive standard of care treatment plus Yaq-001, or standard of care treatment plus placebo). The treatment lasts for 48 weeks. During treatment, the patient will have 6 study visits. 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. On two occasions the patient will have a liver Multiscan and on three occasions the patient will have a liver Fibroscan. 70 patients from 9 hospitals in UK, France, Italy, Portugal, Spain and Switzerland will participate in this study.

Conditions

Non-Alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (18)

• Assessment of reported and observed Serious Adverse Events

  The percentage of patients experiencing SAEs 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 reported and observed Serious Adverse Events

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

  Week 12

• Assessment of reported and observed Serious Adverse Events

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

  Week 24

• Assessment of reported and observed Serious Adverse Events

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

  Week 36

• Assessment of reported and observed Serious Adverse Events

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

  Week 48

• Assessment of treatment-related Serious Adverse Events

  The percentage of patients experiencing device-related 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.

  Week 1

• Assessment of treatment-related Serious Adverse Events

  The percentage of patients experiencing device-related 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 24

• Assessment of treatment-related Serious Adverse Events

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

  Week 36

• Assessment of treatment-related Serious Adverse Events

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

  Week 48

• 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 withdrawals due to Adverse Events

  The percentage of patients who withdraw due to an AE 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 12

• Assessment of withdrawals due to Adverse Events

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

  Week 24

• Assessment of withdrawals due to Adverse Events

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

  Week 36

• Assessment of withdrawals due to Adverse Events

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

  Week 48

Secondary Outcomes (31)

• Determine potential of Yaq-001 for the treatment of NASH

  From Baseline at 48 Weeks

• Determine potential of Yaq-001 for the treatment of NASH

  From Baseline at 48 Weeks

• Determine potential of Yaq-001 for the treatment of NASH

  From Baseline at 24 and 48 weeks

• Determine potential of Yaq-001 for the treatment of NASH

  From Baseline at 24 and 48 weeks

• Determine potential of Yaq-001 for the treatment of NASH

  From Baseline at 24 and 48 weeks

Study Arms (2)

Yaq-001

EXPERIMENTAL

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

Device: Yaq-001

Placebo

PLACEBO COMPARATOR

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

Device: Placebo

Interventions

Yaq-001 DEVICE

Study patients will be dosed daily with 8g of product Yaq-001 for a period of 48 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 54 weeks, including the screening (up to 45 days), treatment (48 weeks) and 7-day follow up period.

Yaq-001

Placebo DEVICE

Study patients will be dosed daily with a quantity of placebo equivalent to 8g of product Yaq-001 for a period of 48 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 54 weeks, including the screening (up to 45 days), treatment (48 weeks) and 7-day follow up period.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 \<70 years at screening
• HbA1C \< 10.5%
• BMI \>25kg/m2
• ALT \<250IU/L
• Ability to provide informed consent
• Agree to the use of effective contraceptive measures if either male or female of child bearing potential.

You may not qualify if:

• History of metabolic acidosis or ketoacidosis
• Presence of vascular liver disease
• Cirrhosis diagnosed either histologically, by laboratory or clinically;
• Presence of liver disease of other aetiology (autoimmune, metabolic, medication induced);
• HIV antibody positive, hepatitis B surface antigen positive (HBsAg) or Hepatitis C virus (HCV)-RNA positive;
• Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 grams per day in females and more than 30 grams per day in males, on average)
• Type 1 diabetes;
• History of bariatric intervention (surgical or endoscopic) performed 6 months or more prior to screening;
• Weight loss or gain of 5kg or more in the past 3 months or \>10% change in bodyweight in the past 3 months;
• Inadequate venous access;
• Lactating/breastfeeding/pregnant at Screening or Baseline;
• Receiving an elemental diet or parenteral nutrition;
• Medical conditions, such as:
• Inflammatory bowel disease;
• Unstable angina, myocardial infarction, transient ischemic events, or stroke within 24 weeks of Screening;

Sponsors & Collaborators

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

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

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: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized (1:1) to: * Standard medical treatment + Yaq-001 (8 g/ day) - n= 35 * Standard medical treatment + placebo-control (placebo for 8 g of Yaq-001/ day) - n= 35

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 24, 2019
• Study Start: January 31, 2021
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2021
• Last Updated: March 3, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

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