Non-Alcoholic SteatohepatitisNCT03962608
Safety and Tolerability of Yaq-001 in Patients With Non-Alcoholic Steatohepatitis
A study testing Yaq-001 in people with Non-Alcoholic Steatohepatitis, run by Yaqrit Ltd at 9 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-Alcoholic Steatohepatitis
- What is being tested?
- Yaq-001
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 9 sitesin 6 countries
- Study dates
- 31 Jan 2021to 31 Jan 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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;
- Active infection
- Active autoimmune disease
- Malignant disease at any time
- Severe congestive heart failure (current medical therapy or current clinical evidence of congestive heart failure NHYA class III/IV) Persistent, uncontrolled hypertension despite optimal medical treatment (for example: Systolic blood pressure (SBP) >160 mmHg or diastolic blood pressure (DBP) >100 mmHg (average of 2 readings) measured in the sitting position at Visit 1, after at least 5 minutes seated rest at screening).
- Any other medical condition which, in the opinion of the investigator, could impact adversely on the subject participating or on the interpretation of the study data
- Presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, haematological, neurological, psychiatric, systemic, ocular, gynaecologic or any acute infectious disease or signs of acute illness that, in the opinion of the investigator, might compromise the patient's safe participation in the trial
- Concurrent medications including:
- Anti-NASH therapy(s) taken for more than 10 continuous days in the last 3 months. These include S-adenosyl methionine (SAM-e), betaine, milk thistle, probiotic supplements (other than yoghurt), vitamin E and gemfibrozil.
- Wash out for any of the anti-NASH therapies is as follows: under 10 days no washout required, more than 10 days and up to 3 months treatment requires 6 weeks washout.
- Use of drugs historically associated with non-alcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins) during the previous year prior to randomization
- Thiazolidinediones (glitazones), or glucagon-like peptide-1 analogues in the last 90 days.
- NOTE: Allowable anti-diabetic treatment includes metformin and/or sulfonylureas and/or dipeptidyl peptidase 4 inhibitors (gliptins) administered at constant dose for at least 2 months prior to study entry
- NOTE: Subjects treated with Insulin are eligible if clinically stable on insulin treatment (i.e. no recurrent acute hypo-/hyperglycaemic episodes diagnosed clinically and by Glucose serum levels of <50 mg/dL and >200 mg/dL respectively) for at least 2 months prior to study entry
- immune modulatory agents including: systemic steroids for more than 7 days; daily treatment with multiple non-steroidal anti-inflammatory drugs (such as aspirin (>100mg/day), ibuprofen, naproxen, meloxicam, celecoxib) for more than 1 month
- Use of ursodeoxycholic acid (Ursodiol, Urso) or obeticholic acid (Ocaliva) within 90 days prior to enrolment
- In the last 6 months:
- azathioprine, 6-mercaptopurine, methotrexate, cyclosporin, anti-TNFα therapies (infliximab, adalimumab, etanercept) or anti-integrin therapies (namixilab)
- More than 10 consecutive days oral or parenteral antibiotics within 4 weeks prior to study entry. NOTE: subjects administered with antibiotics for more the 5 days prior to study entry would not be included in the stool and PBMC analysis
- Within the preceding 4 weeks before treatment:
- immunosuppression, long acting benzodiazepine or barbiturates and antiviral medication
- The following laboratory abnormalities:
- Neutrophil count ≤1.0 x 109/L; Platelets <100 x 109/L
- Haemoglobin <10g/dL; Albumin <3.5g/dL
- International Normalized Ratio (INR) >1.5
- Total bilirubin >1.5 x upper limit of reference range (unless Gilbert's syndrome or extrahepatic source as denoted by increased indirect bilirubin fraction)
- Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 at Screening or Baseline using the Modification of Diet in Renal Disease (MDRD) equation.
- Creatine Phosphokinase >5x ULN
- Past history of acute pancreatitis with current triglycerides 400 mg/dL at Visit 1.
- Any planned major surgery to be performed during the study (e.g., coronary artery bypass surgery, abdominal aortic aneurysm repair, etc.).
- Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities:
- Serum albumin less than 3.4 grams/deciliter (g/dL)
- International Normalized Ratio (INR) greater than 1.3
- Total bilirubin greater than 1.5 milligrams per deciliter (mg/dL)
- Direct bilirubin greater than 0.4 milligrams per deciliter (mg/dL)
- History of esophageal varices, ascites or hepatic encephalopathy
- Evidence of other forms of chronic liver disease:
- Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
- Hepatitis C as defined by presence of hepatitis C virus (HCV) ribonucleic acid (RNA) within last two years.
- Evidence of ongoing autoimmune liver disease as defined by compatible liver histology
- Primary biliary cirrhosis as defined by the presence of at least 2 of these criteria (i) Biochemical evidence of cholestasis based mainly on alkaline phosphatase elevation (ii)Presence of anti-mitochondrial antibody (AMA) (iii)Histologic evidence of non-suppurative destructive cholangitis and destruction of interlobular bile ducts
- Serum creatinine of ≥2.0 mg/dL
- History of biliary diversion
- Participation in any clinical study of an investigational medicinal product within 30 days or five half-lives of the investigational product, whichever is longer.
Trial locations and contacts
9 sites in 6 countries.
9 sites in 6 countries
Spain3 sites
Hospital Vall d'Hebron, Liver Unit
Barcelona, 08035
Hospital Clinic of Barcelona , Liver Unit,
Barcelona, 08036
Hospital Ramon y Cajal, Department of Gastroenterology and Hepatology
Madrid, 28034
Italy2 sites
Policlinico S.Orsola Malpighi, Department of Medical and Surgical Sciences
Bologna, 40138
Azienda Ospedaliera di Padova, Hepatic Emergencies Unit
Padova, 35128
France1 site
Hospital Beaujon, Hepatology and Liver Intensive Care,
Clichy, 82110
Switzerland1 site
Inselspital Universitaet Bern, Department for Visceral Surgery and Medicine
Bern, 3010
United Kingdom1 site
Royal Free Hospital, Institute of Liver and Digestive Disease
London, NW3 2PF
About this study
Official title: Safety and Tolerability of Yaq-001 in Patients With Non-Alcoholic Steatohepatitis ("NASH-Safety")
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.
Read more
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.
Read the 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:
- 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 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.
- Conditions
- Non-Alcoholic Steatohepatitis
- Being tested
- Yaq-001, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Yaq-001Device
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.
PlaceboDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Yaq-001 | Experimental | Standard medical treatment + Yaq-001 (8 g/ day) Receives: Device: Yaq-001 |
| Placebo | Placebo comparator | Standard medical treatment + placebo-control (placebo for 8 g of Yaq-001/ day) Receives: Device: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of reported and observed Serious Adverse Events
The percentage of patients experiencing SAEs will be tabulated by arm.
Measured: Day 1
Assessment of reported and observed Serious Adverse Events
The percentage of patients experiencing SAEs will be tabulated by arm.
Measured: Week 1
Assessment of reported and observed Serious Adverse Events
The percentage of patients experiencing SAEs will be tabulated by arm.
Measured: Week 12
Assessment of reported and observed Serious Adverse Events
The percentage of patients experiencing SAEs will be tabulated by arm.
Measured: Week 24
Assessment of reported and observed Serious Adverse Events
The percentage of patients experiencing SAEs will be tabulated by arm.
Measured: Week 36
Assessment of reported and observed Serious Adverse Events
The percentage of patients experiencing SAEs will be tabulated by arm.
Measured: Week 48
Assessment of treatment-related Serious Adverse Events
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Measured: Day 1
Assessment of treatment-related Serious Adverse Events
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Measured: Week 1
Assessment of treatment-related Serious Adverse Events
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Measured: Week 12
Assessment of treatment-related Serious Adverse Events
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Measured: Week 24
Assessment of treatment-related Serious Adverse Events
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Measured: Week 36
Assessment of treatment-related Serious Adverse Events
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Measured: Week 48
Assessment of withdrawals due to Adverse Events
The percentage of patients who withdraw due to an AE will be tabulated by arm.
Measured: Day 1
Assessment of withdrawals due to Adverse Events
The percentage of patients who withdraw due to an AE will be tabulated by arm.
Measured: Week 1
Assessment of withdrawals due to Adverse Events
The percentage of patients who withdraw due to an AE will be tabulated by arm.
Measured: Week 12
Assessment of withdrawals due to Adverse Events
The percentage of patients who withdraw due to an AE will be tabulated by arm.
Measured: Week 24
Assessment of withdrawals due to Adverse Events
The percentage of patients who withdraw due to an AE will be tabulated by arm.
Measured: Week 36
Assessment of withdrawals due to Adverse Events
The percentage of patients who withdraw due to an AE will be tabulated by arm.
Measured: Week 48
Secondary outcomes (31)
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in hepatic fat fraction (steatosis) as evaluated by MRI -PDFF
Measured: From Baseline at 48 Weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in fibrosis as evaluated by corrected LMS T1 score
Measured: From Baseline at 48 Weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in median stiffness as determined by Fibro-scanning
Measured: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in enhanced liver fibrosis (ELF) scores as non-invasive markers of liver fibrosis
Measured: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in markers of insulin resistance (homeostatic assessment method, HOMA-IR score)
Measured: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in glucose levels
Measured: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in changes in the levels of glycated haemoglobin (HbA1C)
Measured: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Analytical to see the mean change in serum lipid profile
Measured: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Change from baseline in serum levels of cytokeratin (CK)18 - M30 and M65 fractions as indicators of hepatocellular apoptosis and necrosis
Measured: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in microbiome composition
Measured: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in the level of the fibrosis-4 (FIB-4)
Measured: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in the Non-Alcoholic Fatty liver disease fibrosis (NAFLD-F). Fibrosis will be measured by liver multiscan, fibroscan and serological markers of fibrosis defined in the protocol.
Measured: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in liver biochemistry as detected by changes in serum Alanine Aminotransferase (ALT)
Measured: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in liver biochemistry as detected by changes in serum Aspartate transaminase (AST)
Measured: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in liver biochemistry as detected by changes in serum gamma glutamyl transferase (GGT)
Measured: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in liver biochemistry as detected by changes in serum alkaline phosphatase
Measured: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Mean change in alterations in liver biochemistry as detected by changes in serum bilirubin
Measured: From Baseline at 1, 12, 24, 36 and 48 weeks
Assessment of changes in nutritional status
Clinical nutritional assessment, (weight and height will be combined to report BMI in kg/m^2)
Measured: From Baseline at 1, 12, 24, 36, 48 weeks and Termination visit
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Local labs: Vitamin B9
Measured: From Screening, Baseline at 1, 12, 24, 36 and 48 weeks
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Local labs: Vitamin B12
Measured: From Screening, Baseline at 1, 12, 24, 36 and 48 weeks
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Local labs: Vitamin D
Measured: From Screening, Baseline at 1, 12, 24, 36 and 48 weeks
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (blood): Vitamins B1
Measured: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (blood): Vitamins B2
Measured: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (blood): Vitamins B3
Measured: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (blood): Vitamins A
Measured: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (blood): Vitamins E
Measured: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (blood): Vitamins K
Measured: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (blood): zinc (Zn)
Measured: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (blood): Copper (Cu)
Measured: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (blood): Selenium (Se)
Measured: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Laboratory assessment of micronutrients: Core labs (urine): niacin metabolites
Measured: Baseline, Weeks 24 and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2019
- Study start31 Jan 2021 (estimated)
- Primary completion31 Jan 2021 (estimated)
- Study completion31 Jan 2021 (estimated)
Why it stopped: Study was not approved by Health Authorities until get the results of the previous study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic SteatohepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yaqrit Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University College, London, Servicio Madrileño de Salud, Madrid, Spain, Hospital Universitari Vall d'Hebron Research Institute, Azienda Ospedaliera di Padova, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bern, Assistance Publique - Hôpitaux de Paris, University of Lisbon, Alpha Bioresearch S.L., Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Brighton, A2F Associates Limited
- Responsible party
- Sponsor
- Investigators
- Rajiv Jalan, Study chair, Head, Liver Failure Group ILDH, Division of Medicine UCL Medical School Royal Free Campus Rowland Hill Street London NW32PFJane Macnaughtan, Study director, Consultant, Liver Failure Group, ILDH, Division of Medicine UCL Medical School Royal Free Campus Rowland Hill Street London NW32PF
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03962608
- Sponsor's protocol ID
- Yaq001-S-002
- Status last verified
- Feb 2022
- First submitted
- 15 May 2019
- Last updated
- 3 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of Yaq-001 in Patients With Non-Alcoholic Steatohepatitis ("NASH-Safety")
- ClinicalTrials.gov ID
- NCT03962608
- Acronym / sponsor ID
- Yaq001-S-002
- Conditions
- Non-Alcoholic Steatohepatitis
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was not approved by Health Authorities until get the results of the previous study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yaqrit LtdIndustry (pharma, biotech, devices)
- Collaborators
- University College, London, Servicio Madrileño de Salud, Madrid, Spain, Hospital Universitari Vall d'Hebron Research Institute, Azienda Ospedaliera di Padova, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bern, Assistance Publique - Hôpitaux de Paris, University of Lisbon, Alpha Bioresearch S.L., Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Brighton, A2F Associates Limited
- Study start
- 31 Jan 2021 (estimated)
- Primary completion
- 31 Jan 2021 (estimated)
- Study completion
- 31 Jan 2021 (estimated)
- First posted
- 24 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Yaq-001 | Experimental | Device: Yaq-001Standard medical treatment + Yaq-001 (8 g/ day) |
| Placebo | Placebo comparator | Device: PlaceboStandard medical treatment + placebo-control (placebo for 8 g of Yaq-001/ day) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18 <70 years at screening
- HbA1C < 10.5%
- BMI >25kg/m2
- ALT <250IU/L
- Ability to provide informed consent
Key exclusion criteria (58 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Yaq-001Study 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. | Device | Yaq-001 |
| PlaceboStudy 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. | Device | Placebo |
Primary outcome
Assessment of reported and observed Serious Adverse Events
Time frame: Day 1
The percentage of patients experiencing SAEs will be tabulated by arm.
Assessment of reported and observed Serious Adverse Events
Time frame: Week 1
The percentage of patients experiencing SAEs will be tabulated by arm.
Assessment of reported and observed Serious Adverse Events
Time frame: Week 12
The percentage of patients experiencing SAEs will be tabulated by arm.
Assessment of reported and observed Serious Adverse Events
Time frame: Week 24
The percentage of patients experiencing SAEs will be tabulated by arm.
Assessment of reported and observed Serious Adverse Events
Time frame: Week 36
The percentage of patients experiencing SAEs will be tabulated by arm.
Assessment of reported and observed Serious Adverse Events
Time frame: Week 48
The percentage of patients experiencing SAEs will be tabulated by arm.
Assessment of treatment-related Serious Adverse Events
Time frame: Day 1
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Assessment of treatment-related Serious Adverse Events
Time frame: Week 1
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Assessment of treatment-related Serious Adverse Events
Time frame: Week 12
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Assessment of treatment-related Serious Adverse Events
Time frame: Week 24
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Assessment of treatment-related Serious Adverse Events
Time frame: Week 36
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
Assessment of treatment-related Serious Adverse Events
Time frame: Week 48
The percentage of patients experiencing device-related SAEs will be tabulated by arm.
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.
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.
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.
Assessment of withdrawals due to Adverse Events
Time frame: Week 24
The percentage of patients who withdraw due to an AE will be tabulated by arm.
Assessment of withdrawals due to Adverse Events
Time frame: Week 36
The percentage of patients who withdraw due to an AE will be tabulated by arm.
Assessment of withdrawals due to Adverse Events
Time frame: Week 48
The percentage of patients who withdraw due to an AE will be tabulated by arm.
31 secondary outcomes
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 48 Weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 48 Weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 24 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 1, 12, 24, 36 and 48 weeks
Determine potential of Yaq-001 for the treatment of NASH
Time frame: From Baseline at 1, 12, 24, 36 and 48 weeks
Assessment of changes in nutritional status
Time frame: From Baseline at 1, 12, 24, 36, 48 weeks and Termination visit
Assessment of changes in nutritional status
Time frame: From Screening, Baseline at 1, 12, 24, 36 and 48 weeks
Assessment of changes in nutritional status
Time frame: From Screening, Baseline at 1, 12, 24, 36 and 48 weeks
Assessment of changes in nutritional status
Time frame: From Screening, Baseline at 1, 12, 24, 36 and 48 weeks
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Assessment of changes in nutritional status
Time frame: Baseline, Weeks 24 and 48
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rajiv Jalan study chair
Head, Liver Failure Group ILDH, Division of Medicine UCL Medical School Royal Free Campus Rowland Hill Street London NW32PF
Jane Macnaughtan study director
Consultant, Liver Failure Group, ILDH, Division of Medicine UCL Medical School Royal Free Campus Rowland Hill Street London NW32PF
9 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Yaq-001 in people with Non-Alcoholic Steatohepatitis, run by Yaqrit Ltd at 9 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 58 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain, Italy, France, Portugal, Switzerland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of reported and observed Serious Adverse Events (time frame: Day 1). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2022.