Effect of Alpha-1 Antitrypsin Supplementation in Alcohol-Associated Hepatitis-A prospective Pilot Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medizinische Universitaet Innsbruck

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

18 Jun 2025 → ongoing

Decision date (initial)

2025-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Grifols

External identifiers

EU CT number

2024-515794-99-00

ClinicalTrials.gov

NCT06582329

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Primary objective is to evaluate the effect of intravenous A1AT (of 120mg/kg of body weight once a week for 4 weeks) on inflammation in patients with severe AAH.

Secondary objectives 2

1. Secondary objectives are to determine the effects of intravenous AAT on AAT concentrations in serum of patients and the safety and tolerability of AAT. Determination of HRQL.
2. Exploratory objectives are the effects of AAT on inflammation, clinical outcome and surrogates of the severity of liver disease and disease course. In addition, the effect of AAT on fecal microbiome will be assessed.

Conditions and MedDRA coding

Alcohol-Associated Hepatitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Male or female patient ≥18 years of age at time of consent.
2. 2. Severe AAH (Maddrey’s discriminant function score ≥ 32) at screening.
3. 3. No ACLF or ACLF Grade 1 at screening.
4. 4. Daily average intake of >80 g (men)/>60 g (women) ethanol during the past 3 months (patient reported).
5. 5. Understands and agrees to comply with the study procedures and provides written informed consent as documented by signature.
6. 6. Outpatient or hospitalized patient not being on the Intensive Care Unit (ICU) at screening.
7. 7. Negative 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)
8. 8. Male 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.
9. 9. Ability to speak and read German to a level which allows fully comprehending the meaning of everything that is said and written.

Exclusion criteria 9

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 2

1. 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.
2. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medizinische Universitaet Innsbruck

Sponsor organisation

Medizinische Universitaet Innsbruck

Address

Innrain 52

City

Innsbruck

Postcode

6020

Country

Austria

Scientific contact point

Organisation

Medizinische Universitaet Innsbruck

Contact name

University Hospital for Internal Medicine I

Public contact point

Organisation

Medizinische Universitaet Innsbruck

Contact name

University Hospital for Internal Medicine I

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications