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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Non-Alcoholic Steatohepatitis | Device: Yaq-001 Device: Placebo | Not Applicable |
This is a multicentre, randomized, double blinded, placebo controlled trial to intended to evaluate safety and tolerability of oral administration of Yaq-001 therapy.
70 Non-Alcoholic Steatohepatitis patients will be randomized (1:1) to:
Study patients will be dosed daily with Yaq-001 (or an equivalent quantity of placebo) for 48 weeks.
Assessment of DSMB will take place when 15 Yaq-001- and 15 placebo-treated patients have completed 12 weeks of dosing.
Investigational centres specialized in the management of patients with Non-Alcoholic Steatohepatitis will participate in the study.
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.
The total study duration is estimated to be approximately 18 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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 70 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Randomized (1:1) to:
|
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | Placebo |
Primary Purpose: | Treatment |
Official Title: | Safety and Tolerability of Yaq-001 in Patients With Non-Alcoholic Steatohepatitis ("NASH-Safety") |
Estimated Study Start Date : | August 1, 2019 |
Estimated Primary Completion Date : | January 31, 2021 |
Estimated Study Completion Date : | January 31, 2021 |
Arm | Intervention/treatment |
---|---|
Experimental: Yaq-001
Standard medical treatment + Yaq-001 (8 g/ day)
|
Device: Yaq-001
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.
|
Placebo Comparator: Placebo
Standard medical treatment + placebo-control (placebo for 8 g of Yaq-001/ day)
|
Device: Placebo
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.
|
Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Medical conditions, such as:
Concurrent medications including:
Thiazolidinediones (glitazones), or glucagon-like peptide-1 analogues in the last 90 days.
In the last 6 months:
Within the preceding 4 weeks before treatment:
- immunosuppression, long acting benzodiazepine or barbiturates and antiviral medication
The following laboratory abnormalities:
Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities:
Evidence of other forms of chronic liver disease:
Contact: Alicia Navarro Cid | +34917452520 | alicia.navaro@alphabioresearch.com | |
Contact: Sonia Laguna Ueten | +34917452520 | sonia.laguna@alphabioresearch.com |
France | |
Hospital Beaujon, Hepatology and Liver Intensive Care, | |
Clichy, France, 82110 | |
Contact: François Durand + 33 01 40 87 50 00 | |
Italy | |
Policlinico S.Orsola Malpighi, Department of Medical and Surgical Sciences | |
Bologna, Italy, 40138 | |
Contact: Paolo Caraceni + 39 051 636 2 919 | |
Azienda Ospedaliera di Padova, Hepatic Emergencies Unit | |
Padova, Italy, 35128 | |
Contact: Paolo Angeli +39 049 821 2 004 | |
Portugal | |
University Hospital of Santa Maria | |
Lisbon, Portugal, 1649-035 | |
Contact: Helena Cortez-Pinto +351 21 780 5000 | |
Spain | |
Hospital Vall d'Hebron, Liver Unit | |
Barcelona, Spain, 08035 | |
Contact: Victor Vargas +34 93 489 30 00 | |
Hospital Clinic of Barcelona , Liver Unit, | |
Barcelona, Spain, 08036 | |
Contact: Pere Gines +34 93 227 17 13 | |
Hospital Ramon y Cajal, Department of Gastroenterology and Hepatology | |
Madrid, Spain, 28034 | |
Contact: Agustin Albillos +34 91 336 85 92 | |
Switzerland | |
Inselspital Universitaet Bern, Department for Visceral Surgery and Medicine | |
Bern, Switzerland, 3010 | |
Contact: Reiner Wiest +41 31 632 0291 | |
United Kingdom | |
Royal Free Hospital, Institute of Liver and Digestive Disease | |
London, United Kingdom, NW3 2PF | |
Contact: Gautam Mehta +44 207 794 0500 |
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 |
Tracking Information | |||||||
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First Submitted Date ICMJE | May 15, 2019 | ||||||
First Posted Date ICMJE | May 24, 2019 | ||||||
Last Update Posted Date | May 24, 2019 | ||||||
Estimated Study Start Date ICMJE | August 1, 2019 | ||||||
Estimated Primary Completion Date | January 31, 2021 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | No Changes Posted | ||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Safety and Tolerability of Yaq-001 in Patients With Non-Alcoholic Steatohepatitis | ||||||
Official Title ICMJE | Safety and Tolerability of Yaq-001 in Patients With Non-Alcoholic Steatohepatitis ("NASH-Safety") | ||||||
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. |
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Detailed Description |
This is a multicentre, randomized, double blinded, placebo controlled trial to intended to evaluate safety and tolerability of oral administration of Yaq-001 therapy. 70 Non-Alcoholic Steatohepatitis patients will be randomized (1:1) to:
Study patients will be dosed daily with Yaq-001 (or an equivalent quantity of placebo) for 48 weeks. Assessment of DSMB will take place when 15 Yaq-001- and 15 placebo-treated patients have completed 12 weeks of dosing. Investigational centres specialized in the management of patients with Non-Alcoholic Steatohepatitis will participate in the study. 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. The total study duration is estimated to be approximately 18 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. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Not Applicable | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Randomized (1:1) to:
Masking Description: Placebo Primary Purpose: Treatment
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Condition ICMJE | Non-Alcoholic Steatohepatitis | ||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Unknown status | ||||||
Estimated Enrollment ICMJE |
70 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | January 31, 2021 | ||||||
Estimated Primary Completion Date | January 31, 2021 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 70 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | France, Italy, Portugal, Spain, Switzerland, United Kingdom | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03962608 | ||||||
Other Study ID Numbers ICMJE | Yaq001-S-002 | ||||||
Has Data Monitoring Committee | No | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Yaqrit Ltd | ||||||
Study Sponsor ICMJE | Yaqrit Ltd | ||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Yaqrit Ltd | ||||||
Verification Date | May 2019 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |