Phase II, double-blind, randomized, placebo-controlled, multicentre study to evaluate the safety, efficacy, and pharmacokinetics of TAK-242 and Granulocyte Colony-Stimulating Factor (G-CSF) (G-TAK) in subjects with severe alcoholic hepatitis (sAH) and acute-on-chronic liver failure (ACLF)
- Conditions
- Severe alcoholic hepatitis (sAH) and acute-on-chronic liver failure (ACLF)Digestive SystemAlcoholic hepatitis
- Registration Number
- ISRCTN36798599
- Lead Sponsor
- Yaqrit Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 78
1. Male and female subjects =18 years of age and =75 years of age
2. With a diagnosis of severe alcoholic hepatitis defined by a Lille score of >0.45 in those treated with steroids and/or contraindication to steroids
3. Eligible subjects will have Grade 1- 3 ACLF with a maximum of three organ failures using the CLIF-C OF score AND the CLIF-C ACLF-CRP score of >35 and <60
1. Refusal to give informed consent
2. Mechanical ventilation due to respiratory failure and/or need for renal replacement therapy and or requiring inotropes for circulatory support with a noradrenaline requirement of >0.5 ug/kg/min to maintain mean arterial pressure >70 mmHg
3. Subject has received any investigational drug within 30 days of randomization
4. Subject has any of the following conditions:
4.1. History of liver transplantation
4.2. Postoperative decompensation after partial hepatectomy
4.3. Liver failure without evidence of underlying chronic liver disease
5. Any untreated infections (<48h antibiotic therapy) including gram-positive infections, active tuberculosis or coinfection with HIV
6. Chronic or pre-existing kidney failure, survival prognosis of <6 months due to severe co-morbid conditions that might confound study results or compromise subject safety
7. Methemoglobinemia, clinically-significant disseminated intravascular coagulation, uncontrolled bleeding, sickle cell anaemia
8. Uncontrolled seizures, Creutzfeldt-Jakob disease, glucose-6-phosphate dehydrogenase deficiency
9. Active malignancy, premalignant haematological disorders (e.g. myelodysplastic syndrome, chronic myeloid leukaemia) or multiorgan failure (=4 organ failures)
10. Pregnancy or nursing women
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> The safety of TAK-242 in combination with G-CSF and alone in subjects with sAH and ACLF compared to placebo from baseline to Day 14, assessed using:<br> 1. The percentage of subjects who experience at least one treatment-emergent AE (TEAE) or SAE<br> 2. The percentage of subjects who discontinue the study drug due to an AE (including methemoglobinemia)<br> 3. The percentage of subjects who experience at least one treatment-emergent clinical laboratory test result or abnormal ECG that meets the Sponsor’s markedly abnormal criteria<br>
- Secondary Outcome Measures
Name Time Method