Alcohol-Associated HepatitisPhase 2EARTHNCT06582329
Effect of Alpha-1 Antitrypsin Supplementation on Alcohol-Associated Hepatitis
A Phase 2 study testing Alfa1 Antitrypsin in people with Alcohol-Associated Hepatitis, run by Medical University Innsbruck at 1 site in Austria.
Trial summary
The trial is designed as a prospective, single center, open label, randomized controlled pilot study evaluating the effect of A1AT (Alpha 1 Antitrypsin) on inflammation in patients with severe AAH (alcohol-associated hepatitis). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcohol-Associated Hepatitis
- What is being tested?
- Alfa1 Antitrypsin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteAustria
- Study dates
- 18 Jun 2025to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patient ≥18 years of age at time of consent.
- Severe AAH (Maddrey's discriminant function score ≥ 32) at screening.
- No ACLF or ACLF Grade 1 at screening.
- Daily average intake of >80 g (men)/>60 g (women) ethanol during the past 3 months (patient reported).
- Understands and agrees to comply with the study procedures and provides written informed consent as documented by signature.
- Outpatient or hospitalized patient not being on the Intensive Care Unit (ICU) at screening.
Show all 10Show fewer
- Inclusion criterion 7 only applies to women of childbearing potential (WOCBP)
- 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 cervical cap) used in conjunction with spermicide; intrauterine device; prescription hormonal contraceptive taken or administered via oral (pill), transdermal (patch), subdermal, or intramuscular (IM) route Inclusion criterion 8 only applies to male patients
- Male patients who are sexually active with female partners of childbearing potential must agree to use a condom with 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.
- Ability to speak and read German to a level which allows fully comprehending the meaning of everything that is said and written.
Who cannot join
- Uncontrolled Diabetes Mellitus type 1 or 2 (defined by HbA1c > 10%).
- Corticosteroid use contraindicated.
- Viral hepatitis, autoimmune hepatitis, HIV infection, Wilson disease, hemochromatosis, toxic liver injury, Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC).
- Participation in another interventional clinical study within 6 months prior to screening and/or during trial participation.
- Presence of any active malignancy (other than non-melanoma skin cancer) which required treatment within the past 12 months.
- Chronic kidney disease receiving dialysis.
Show all 9Show fewer
- Do Not Attempt Resuscitation (DNAR) order in place.
- IgA deficiency (IgA level <7mg/dL) or known intolerance to A1AT.
- History of liver transplantation or currently listed for liver transplant.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Austria1 site, 1 recruiting
- Recruiting
Medical University Innsbruck
Innsbruck
Medical University Innsbruck MUI Principal Investigator, +43 050504
About this study
Official title: Effect of Alpha-1 Antitrypsin Supplementation on Alcohol-Associated Hepatitis - A Prospective Pilot Study
The trial is designed as a prospective, single center, open label, randomized controlled pilot study evaluating the effect of A1AT (Alpha 1 Antitrypsin) on inflammation in patients with severe AAH (alcohol-associated hepatitis).
The objective is to evaluate the safety and the effect of intravenous A1AT on the systemic inflammation in patients with severe AAH. The objectives also include the assessment of A1AT on clinical outcomes including the incidence of adverse events (AEs) and serious adverse events (SAEs) and the cytokine.
Read the detailed description
About 5-7 % of patients with alcohol-associated chronic liver disease transform into acute on chronic liver disease (ACLF) per year. In patients with underlying alcohol-associated liver disease (ALD) and active drinking, a sudden onset of jaundice, malaise, decompensated liver disease and coagulopathy i.e. alcohol-associated hepatitis (AAH) might develop. In its severe form, AAH is associated with development of ACLF and bacterial infections and this disease exhibits a high short-term mortality of 20 to 50% within 3 months. Treatment options are limited currently, for instance, the use of corticosteroids.
Alpha-1 Antitrypsin (A1AT) acts as an anti-inflammatory protein by inhibiting the generation of pro-inflammatory cytokines. The investigators recently showed protective effects of A1AT in a pre-clinical experimental model of ALD, resulting in decreased levels of pro-inflammatory cytokines, less steatosis and hepatic injury. The investigators also have recently found that cirrhotic patients with A1AT concentrations less than 120 mg/dL had a significantly increased risk for death/liver transplantation in a cohort of 130 patients with ALD cirrhosis. This finding was not only significant, but also independent of the MELD-Na score, indicating that in ALD A1AT is not only a marker of reduced hepatic synthetic function. Further, significantly higher ferritin and lower transferrin in the cohort of patients with low A1AT also indicate more severe inflammation. An interventional analysis in an established mouse model of ALD showed that A1AT supplementation mitigated inflammation and histological changes further indicating that low AAT (Alpha 1 Antitrypsin) is a driver and not the consequence of tissue damage in ALD. These data support the use of A1AT in humans with severe AAH.
As a pilot trial the study also aims to establish important preliminary data for future studies and design of larger trials aimed at formal evaluation of the effect of A1AT on clinical endpoints.
- Conditions
- Alcohol-Associated Hepatitis
- Being tested
- Alfa1 Antitrypsin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alfa1 AntitrypsinDrug
Participants will be treated intravenously with A1AT 120 mg/kg bodyweight once a week for 4 weeks (4 total infusions).
| Study group | Role | What they receive |
|---|---|---|
| standard of care | No intervention | Standard of care Prednisolon 40mg will be administered over 4 weeks |
| Standard of care + Alpha 1 Antitrypsin | Experimental | In the experimental arm the participants will receive Prolastin 120 mg/kg bodyweight and Prednisolon 40 mg over a time period of 4 weeks Receives: Drug: Alfa1 Antitrypsin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum concentration of IL-6 (interleukin-6) assessed at Visit 2 (Day 8+/-1) in the intervention (A1AT in combination with standard-of-care) and control group (standard-of-care).
The effect on the serum IL-6 concentration assessed after 1 week will be assessed at Visit 2 (Day 8+/-1) in the intervention (A1AT in combination with standard-of-care) and control group (standard-of-care).
Measured: at visit 2
Secondary outcomes (5)
Serum A1AT concentration assessed at visit 5 (Day 29+/-3)
Measured: at visit 5 (Day 29+/-3)
Incidence of Adverse Events (AEs) from the baseline visit (Day 1) to end of study visit (Day 90+/-7)
Measured: up to 3 months
Incidence of Serious Adverse Events (SAEs) from the baseline visit (Day 1) through to end of study visit (Day 90+/-7)
Measured: up to 3 months
Chronic Liver Disease Questionnaire (CLDQ) overall and subscale scores.
The response of CLDQ results in 1 to 7 scales, ranging from "all the time" to "none of the time". Higher scores indicate the minimum frequency of symptoms and therefore a better HRQL
Measured: up to 3 months
CLDQ-D overall and subscale scores
The response of CLDQ results in 1 to 7 scales, ranging from "all the time" to "none of the time". Higher scores indicate the minimum frequency of symptoms and therefore a better HRQL.
Measured: up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2024
- Study start18 Jun 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol-Associated HepatitisStudies of the same condition, open and under way.
- More trials run by Medical University InnsbruckThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Therapeutic exploratory trial: the trial is designed as a prospective, single center, open label, randomized controlled pilot study
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University Innsbruck
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06582329
- Sponsor's protocol ID
- EARTH-2024
- Acronym
- EARTH
- Status last verified
- Feb 2026
- First submitted
- 31 Jul 2024
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Alpha-1 Antitrypsin Supplementation on Alcohol-Associated Hepatitis - A Prospective Pilot Study
- ClinicalTrials.gov ID
- NCT06582329
- Acronym / sponsor ID
- EARTH / EARTH-2024
- Conditions
- Alcohol-Associated Hepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Medical University InnsbruckUniversity, hospital or other
- Study start
- 18 Jun 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 3 Sep 2024 (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.
The trial is designed as a prospective, single center, open label, randomized controlled pilot study evaluating the effect of A1AT (Alpha 1 Antitrypsin) on inflammation in patients with severe AAH (alcohol-associated hepatitis).
The objective is to evaluate the safety and the effect of intravenous A1AT on the systemic inflammation in patients with severe AAH. The objectives also include the assessment of A1AT on clinical outcomes including the incidence of adverse events (AEs) and serious adverse events (SAEs) and the cytokine.
Detailed description
About 5-7 % of patients with alcohol-associated chronic liver disease transform into acute on chronic liver disease (ACLF) per year. In patients with underlying alcohol-associated liver disease (ALD) and active drinking, a sudden onset of jaundice, malaise, decompensated liver disease and coagulopathy i.e. alcohol-associated hepatitis (AAH) might develop. In its severe form, AAH is associated with development of ACLF and bacterial infections and this disease exhibits a high short-term mortality of 20 to 50% within 3 months. Treatment options are limited currently, for instance, the use of corticosteroids.
Alpha-1 Antitrypsin (A1AT) acts as an anti-inflammatory protein by inhibiting the generation of pro-inflammatory cytokines. The investigators recently showed protective effects of A1AT in a pre-clinical experimental model of ALD, resulting in decreased levels of pro-inflammatory cytokines, less steatosis and hepatic injury. The investigators also have recently found that cirrhotic patients with A1AT concentrations less than 120 mg/dL had a significantly increased risk for death/liver transplantation in a cohort of 130 patients with ALD cirrhosis. This finding was not only significant, but also independent of the MELD-Na score, indicating that in ALD A1AT is not only a marker of reduced hepatic synthetic function. Further, significantly higher ferritin and lower transferrin in the cohort of patients with low A1AT also indicate more severe inflammation. An interventional analysis in an established mouse model of ALD showed that A1AT supplementation mitigated inflammation and histological changes further indicating that low AAT (Alpha 1 Antitrypsin) is a driver and not the consequence of tissue damage in ALD. These data support the use of A1AT in humans with severe AAH.
As a pilot trial the study also aims to establish important preliminary data for future studies and design of larger trials aimed at formal evaluation of the effect of A1AT on clinical endpoints.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Therapeutic exploratory trial: the trial is designed as a prospective, single center, open label, randomized controlled pilot study
| Arm | Type | Receives |
|---|---|---|
| standard of care | No intervention | –Standard of care Prednisolon 40mg will be administered over 4 weeks |
| Standard of care + Alpha 1 Antitrypsin | Experimental | Drug: Alfa1 AntitrypsinIn the experimental arm the participants will receive Prolastin 120 mg/kg bodyweight and Prednisolon 40 mg over a time period of 4 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female patient ≥18 years of age at time of consent.
- Severe AAH (Maddrey's discriminant function score ≥ 32) at screening.
- No ACLF or ACLF Grade 1 at screening.
- Daily average intake of >80 g (men)/>60 g (women) ethanol during the past 3 months (patient reported).
- Understands and agrees to comply with the study procedures and provides written informed consent as documented by signature.
Key exclusion criteria (9 listed)
- Uncontrolled Diabetes Mellitus type 1 or 2 (defined by HbA1c > 10%).
- Corticosteroid use contraindicated.
- Viral hepatitis, autoimmune hepatitis, HIV infection, Wilson disease, hemochromatosis, toxic liver injury, Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC).
- Participation in another interventional clinical study within 6 months prior to screening and/or during trial participation.
- Presence of any active malignancy (other than non-melanoma skin cancer) which required treatment within the past 12 months.
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 |
|---|---|---|
| Alfa1 AntitrypsinParticipants will be treated intravenously with A1AT 120 mg/kg bodyweight once a week for 4 weeks (4 total infusions). | Drug | Standard of care + Alpha 1 Antitrypsin |
Primary outcome
Serum concentration of IL-6 (interleukin-6) assessed at Visit 2 (Day 8+/-1) in the intervention (A1AT in combination with standard-of-care) and control group (standard-of-care).
Time frame: at visit 2
The effect on the serum IL-6 concentration assessed after 1 week will be assessed at Visit 2 (Day 8+/-1) in the intervention (A1AT in combination with standard-of-care) and control group (standard-of-care).
5 secondary outcomes
Serum A1AT concentration assessed at visit 5 (Day 29+/-3)
Time frame: at visit 5 (Day 29+/-3)
Incidence of Adverse Events (AEs) from the baseline visit (Day 1) to end of study visit (Day 90+/-7)
Time frame: up to 3 months
Incidence of Serious Adverse Events (SAEs) from the baseline visit (Day 1) through to end of study visit (Day 90+/-7)
Time frame: up to 3 months
Chronic Liver Disease Questionnaire (CLDQ) overall and subscale scores.
Time frame: up to 3 months
CLDQ-D overall and subscale scores
Time frame: up to 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
Related trials for Alcohol-Associated Hepatitis
RecruitingPhase 3
Study to Evaluate the Safety and Efficacy of Larsucosterol in Participants With Alcohol-associated Hepatitis (AH)
Hepatitis
Active, not recruitingPhase 3
Efficacy Of Bovine Colostrum In The Treatment Of Severe Alcohol-Associated Hepatitis: A Randomized Controlled Trial
Alcoholic Hepatitis
RecruitingPhase 2
Integrated Therapies for Alcohol Use in Alcohol-associated Liver Disease (ITAALD) Trial
Alcohol-associated Hepatitis
Not yet recruiting
Financial Rewards for Reducing Alcohol Use in Patients With Liver Disease
Alcohol Use Disorder, Alcohol-associated Liver Disease
Not yet recruitingPhase 1
Safety and Tolerability of NTR-101 in Patients With Acute Alcohol-Associated Hepatitis
Alcohol-Associated Hepatitis
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alfa1 Antitrypsin in people with Alcohol-Associated Hepatitis, run by Medical University Innsbruck at 1 site in Austria.
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 10 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum concentration of IL-6 (interleukin-6) assessed at Visit 2 (Day 8+/-1) in the intervention (A1AT in combination with standard-of-care) and control group (standard-of-care). (time frame: at visit 2). 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 9 Oct 2026.