HUMAN ALPHA1-PROTEINASE INHIBITOR for Alcohol-associated hepatitis

Inclusion criteria

• {"criterion_text":"- 1.\tMale or female patient ≥18 years of age at time of consent."}
• {"criterion_text":"- 2.\tSevere AAH (Maddrey’s discriminant function score ≥ 32) at screening."}
• {"criterion_text":"- 3.\tNo ACLF or ACLF Grade 1 at screening."}
• {"criterion_text":"- 4.\tDaily average intake of >80 g (men)/>60 g (women) ethanol during the past 3 months (patient reported)."}
• {"criterion_text":"- 5.\tUnderstands and agrees to comply with the study procedures and provides written informed consent as documented by signature."}
• {"criterion_text":"- 6.\tOutpatient or hospitalized patient not being on the Intensive Care Unit (ICU) at screening."}
• {"criterion_text":"- 7.\tNegative urine pregnancy test, not breastfeeding & agreement to use highly-effective means of contraception during the study. Allowed are sexual abstinence, vasectomized partners (˃3 months previously-vasectomy has to be confirmed by two negative semen analyses) or the consistent and correct use of an approved contraceptive method in accordance with the product label, for example: Barrier method (such as condoms, diaphragm, or cercival cap) used in conjunction with spermicide; intrauterine device; prescription hormonal contraceptive taken or administered via oral (pill), transdermal (patch), subdermal, or IM route. Inclusion criterion 7 only applies to women of childbearing potential (WOCBP)"}
• {"criterion_text":"- 8.\tMale patients who are sexually active with female partners of childbearing potential must agree to use a condom. Inclusion criterion 8 only applies to male patientswith spermicide and to use one other approved method of highly effective contraception from the time of investigational product administration for at least 90 days after the dose of investigational product and must refrain from sperm donation from Screening through at least 90 days following the last dose of investigational product."}
• {"criterion_text":"- 9.\tAbility to speak and read German to a level which allows fully comprehending the meaning of everything that is said and written."}

Exclusion criteria

• {"criterion_text":"- 1.\tUncontrolled Diabetes Mellitus type 1 or 2 (as defined by HbA1c > 10%)."}
• {"criterion_text":"- 2.\tCorticosteroid use contraindicated."}
• {"criterion_text":"- 3.\tViral hepatitis, autoimmune hepatitis, HIV infection, Wilson disease, hemochromatosis, toxic liver injury, Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC)."}
• {"criterion_text":"- 4.\tParticipation in another interventional clinical study within 6 months prior to screening and/or during study participation."}
• {"criterion_text":"- 5.\tPresence of any active malignancy (other than non-melanoma skin cancer) which required treatment within the past 12 months."}
• {"criterion_text":"- 6.\tChronic kidney disease receiving dialysis."}
• {"criterion_text":"- 7.\tDo Not Attempt Resuscitation (DNAR) order in place."}
• {"criterion_text":"- 8.\tIgA deficiency (IgA level <7mg/dL) or known intolerance to A1AT."}
• {"criterion_text":"- 9.\tHistory of liver transplantation or currently listed for liver transplant."}

Primary endpoints

• {"endpoint_text":"- Serum concentration of IL-6 assessed at Visit 2 (Day 8+/-1) in the intervention (A1AT in combination with standard-of-care) and control group (standard-of-care).","definition_or_measurement_approach":"Measured as serum concentration of IL-6 at Visit 2 (Day 8 ±1) comparing intervention (A1AT + standard-of-care) and control (standard-of-care)."}

Secondary endpoints

• {"endpoint_text":"- The secondary endpoints are: (i) serum A1AT concentration assessed at visit 5 (Day 29+/-3); (ii) incidence of Adverse Events (AEs) from the baseline visit (Day 1) to end of study visit (Day 90+/-7); and (iii) incidence of Serious Adverse Events (SAEs) from the baseline visit (Day 1) through to end of study visit (Day 90+/-7). CLDQ-D overall and subscale scores.","definition_or_measurement_approach":"Serum A1AT concentration measured at Visit 5 (Day 29 ±3). Incidence of AEs and SAEs assessed from baseline (Day 1) to End of Study Visit (Day 90 ±7). Health-related quality of life measured using CLDQ-D overall and subscale scores."}

Other endpoints

• {"endpoint_text":"- Exploratory endpoints: Clinical disease scores : CLDQ-D overall and subscale scores, MELD, MELD-Na, Child-Pugh-Turcotte, CLIF-C-AD, CLIF-C-OF, CLIF-SOFA score, Maddrey’s discriminant function. Clinical outcome: time to hospital discharge, time to re-hospitalization, time to ICU admission, liver-specific survival and transplant-free survival at End of Study Visit. Serum concentrations of IL-6","definition_or_measurement_approach":"Multiple clinical disease scores (CLDQ-D, MELD, MELD-Na, Child-Pugh, CLIF indices, Maddrey’s) assessed as specified; clinical outcomes measured as time-to-event endpoints (time to discharge, re-hospitalization, ICU admission, liver-specific survival, transplant-free survival at End of Study Visit). Serum IL-6 concentrations also measured (timing specified in protocol)."}

Austria

Earliest CTIS Part Ii Submission Date

26-11-2024

Latest Decision Or Authorization Date

15-01-2025

Processing Time Days

50

Number Of Sites

1

Number Of Participants

16

Primary sponsor

Full Name

Medizinische Universitaet Innsbruck

Organisation Type

Educational Institution

Country Of Registered Address

Austria

Third parties

• {"country":"","full_name":"Grifols","duties_or_roles":"Source of monetary support","organisation_type":""}