Effect of Alpha-1 Antitrypsin Supplementation on Alcohol-Associated Hepatitis

NCT06582329 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: EARTH-2024
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Alcohol-Associated Hepatitis

Outcome Measures

Primary Outcomes (1)

• 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).

  at visit 2

Secondary Outcomes (5)

• Serum A1AT concentration assessed at visit 5 (Day 29+/-3)

  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)

  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)

  up to 3 months

• Chronic Liver Disease Questionnaire (CLDQ) overall and subscale scores.

  up to 3 months

• CLDQ-D overall and subscale scores

  up to 3 months

Other Outcomes (12)

• Model for end-stage liver disease (MELD)

  up to 3 months

• The MELD-sodium (MELD-Na)

  up to 3 months

• Child-Pugh-Turcotte

  up to 3 months

Study Arms (2)

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

Drug: Alfa1 Antitrypsin

Interventions

Alfa1 Antitrypsin DRUG

Participants will be treated intravenously with A1AT 120 mg/kg bodyweight once a week for 4 weeks (4 total infusions).

Standard of care + Alpha 1 Antitrypsin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Medical University Innsbruck: lead

Study Sites (1)

Medical University Innsbruck

Innsbruck, Austria

Location

MeSH Terms

Interventions

alpha 1-Antitrypsin

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Therapeutic exploratory trial: the trial is designed as a prospective, single center, open label, randomized controlled pilot study

Study Record Dates

• First Submitted: July 31, 2024
• First Posted: September 3, 2024
• Study Start: April 1, 2025
• Primary Completion: July 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 6, 2025

Record last verified: 2024-08

Locations

AU (1)