What side effects are associated with this type of intervention?

The most common treatment for Alpha-1 Antitrypsin Deficiency is intravenous augmentation therapy, which involves regular infusions of alpha-1 antitrypsin protein. Known side effects of this treatment include headache, dizziness, fever, chills, and flu-like symptoms. Some patients may also experience injection site reactions such as pain, swelling, and redness. In rare cases, there can be allergic reactions, including anaphylaxis. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate any adverse effects effectively.

What prior FDA approvals exist?

The FDA has approved several Alpha-1 Proteinase Inhibitor (A1PI) products for the treatment of Alpha-1 Antitrypsin Deficiency (AATD), including Prolastin, Aralast, Zemaira, and Glassia. These intravenous therapies aim to increase A1AT levels in the blood and lungs to slow the progression of emphysema in AATD patients. The study on Alpha-1 15% is exploring a subcutaneous form of A1PI, potentially offering a more convenient administration route.

What other types of research exist?

Promising novel alternatives to Alpha-1 15% for AATD patients include gene therapy approaches aimed at correcting the underlying genetic defect, and advanced protein replacement therapies that deliver recombinant alpha-1 antitrypsin more effectively. These therapies are still in various stages of research and development but hold potential for more effective and long-lasting treatment outcomes.

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Proteinase Inhibitor

Alpha1-Proteinase Inhibitor for Alpha-1 Antitrypsin Deficiency

Phase 1 & 2

Recruiting

Research Sponsored by Grifols Therapeutics LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have a diagnosis of congenital Alpha1-antitrypsin deficiency (AATD) with specific allelic combinations

Have a documented pre-Alpha1-Proteinase Inhibitor (PI) augmentation therapy serum alpha-1 antitrypsin (AAT) level below specified thresholds

Must not have

Females who are pregnant, breastfeeding or, if of child-bearing potential, unwilling to practice a highly effective method of contraception throughout the study

Use systemic steroids above a stable dose equivalent to 5 mg/day prednisone within the 4 weeks prior to the Week 1 (Baseline) Visit

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if Alpha-1 protein injections are safe and tolerable for people with Alpha1-Antitrypsin Deficiency. The treatment aims to protect their lungs by giving them extra Alpha-1 protein. Alpha-1 proteinase inhibitor, a human-derived blood product, has been used for over 20 years to treat individuals with Alpha1-Antitrypsin Deficiency.

Who is the study for?

This trial is for individuals with Alpha1-Antitrypsin Deficiency (AATD) who have low serum AAT levels and specific lung function measurements. Participants can be new or current on Alpha1-PI therapy but must stop it before the study starts. Pregnant women, those not using effective contraception, people with severe allergies to plasma-derived treatments, recent lung surgery patients, or those with certain health conditions are excluded.

What is being tested?

The study tests two doses of a medication called Alpha-1 15%, given as a subcutaneous infusion in participants with AATD. The first dose is administered once and then weekly over eight weeks to evaluate safety and how the body processes the drug.

What are the potential side effects?

While specific side effects aren't listed here, common ones for similar treatments may include injection site reactions, possible allergic responses especially in those sensitive to plasma products, headaches, fatigue, and flu-like symptoms.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with Alpha1-antitrypsin deficiency.

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My alpha-1 antitrypsin levels are below the required threshold.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not pregnant, breastfeeding, and if able to bear children, I agree to use effective birth control during the study.

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I haven't increased my steroid dose above 5 mg/day prednisone in the last 4 weeks.

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I have had a serious worsening of my COPD in the last 4 weeks.

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I have had a lung or liver transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Cohort 2: Treatment Period 2 (Alpha-1 15%, 180 mg/kg)Experimental Treatment1 Intervention

Following treatment period 1 and single-dose data evaluation phase, participants in Cohort 2 will enter treatment period 2 (Repeat-Dose) and will receive Alpha-1 15% 180 mg/kg, for 8 weekly SC infusions.

Group II: Cohort 2: Treatment Period 1 (Alpha-1 15%, 180 mg/kg)Experimental Treatment1 Intervention

Participants will receive Alpha-1 15% 180 mg/kg, single weekly SC infusion in treatment-period 1 (Single-Dose) at Week 1.

Group III: Cohort 2: Single-Dose Data Evaluation Period (Liquid Alpha1-Proteinase Inhibitor 120 mg/kg)Experimental Treatment1 Intervention

Following treatment period 1, participants in Cohort 2 will enter 21 days of washout/serial pharmacokinetic (PK) phase and then the single-dose data evaluation phase. During the single-dose data evaluation phase, Liquid Alpha1-PI 120 mg/kg, weekly IV Infusions will be administered from intravenous-dose Week 1 (single-dose Week 5) for up to Week 78, with the last IV dose given 1 week prior to the first repeat Alpha-1 15% SC dose.

Group IV: Cohort 1: Treatment Period 2 (Alpha-1 15%, 72 mg/kg)Experimental Treatment1 Intervention

Following treatment period 1 and single-dose data evaluation period, participants in Cohort 1 will enter treatment period 2 (Repeat-Dose) and will receive Alpha-1 15% 72 mg/kg, for 8 weekly SC infusions.

Group V: Cohort 1: Treatment Period 1 (Alpha-1 15%, 72 mg/kg)Experimental Treatment1 Intervention

Participants will receive Alpha-1 15% 72 mg/kg, single weekly subcutaneous (SC) infusion in treatment-period 1 (Single-Dose) at Week 1.

Group VI: Cohort 1: Single-Dose Data Evaluation Period (Liquid Alpha 1-Proteinase Inhibitor 60 mg/kg)Experimental Treatment1 Intervention

Following treatment period 1, participants in Cohort 1 will enter 21 days of washout/serial pharmacokinetic (PK) phase and then the single-dose data evaluation period. During the single-dose data evaluation phase, Liquid Alpha1- Proteinase Inhibitor (PI) 60 mg/kg, weekly intravenous (IV) Infusions will be administered from intravenous-dose Week 1 (single-dose Week 5) for up to Week 78, with the last IV dose given 1 week prior to the first repeat Alpha-1 15% SC dose.

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Augmentation therapy for Alpha-1 Antitrypsin Deficiency (AATD) involves administering alpha-1 proteinase inhibitor (A1-PI) to raise the levels of this protective protein in the blood and lungs. This therapy helps shield lung tissue from damage by neutrophil elastase, an enzyme that can degrade proteins and cause severe lung damage in AATD patients. By boosting A1-PI levels, augmentation therapy aims to slow lung disease progression, which is vital for improving the quality of life and reducing exacerbations and hospitalizations in AATD patients.

Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease.The intrapulmonary half-life and safety of aerosolized alpha1-protease inhibitor in normal volunteers.