A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants With Alpha1-Antitrypsin Deficiency

NCT ID: NCT04722887

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-13
• Study Completion Date: 2025-08-01

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of 72 milligrams per kilogram (mg/kg) and 180 mg/kg Alpha-1 15%, administered as a single-dose subcutaneous (SC) infusion and subsequently as weekly SC infusions over 8 weeks in participants with Alpha1-Antitrypsin Deficiency (AATD).

Conditions

Alpha1-Antitrypsin Deficiency

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Treatment Period 1 (Alpha-1 15%, 72 mg/kg)

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

Group Type: EXPERIMENTAL

Alpha-1 15%

Intervention Type: BIOLOGICAL

Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion

Cohort 1: Single-Dose Data Evaluation Period (Liquid Alpha 1-Proteinase Inhibitor 60 mg/kg)

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.

Group Type: EXPERIMENTAL

Liquid Alpha1-Proteinase Inhibitor (Human)

Intervention Type: BIOLOGICAL

Intravenous infusion

Cohort 1: Treatment Period 2 (Alpha-1 15%, 72 mg/kg)

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 Type: EXPERIMENTAL

Alpha-1 15%

Intervention Type: BIOLOGICAL

Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion

Cohort 2: Treatment Period 1 (Alpha-1 15%, 180 mg/kg)

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

Group Type: EXPERIMENTAL

Alpha-1 15%

Intervention Type: BIOLOGICAL

Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion

Cohort 2: Single-Dose Data Evaluation Period (Liquid Alpha1-Proteinase Inhibitor 120 mg/kg)

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 Type: EXPERIMENTAL

Liquid Alpha1-Proteinase Inhibitor (Human)

Intervention Type: BIOLOGICAL

Intravenous infusion

Cohort 2: Treatment Period 2 (Alpha-1 15%, 180 mg/kg)

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 Type: EXPERIMENTAL

Alpha-1 15%

Intervention Type: BIOLOGICAL

Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion

Interventions

Alpha-1 15%

Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion

Intervention Type: BIOLOGICAL

Liquid Alpha1-Proteinase Inhibitor (Human)

Intravenous infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

Prolastin®-C Liquid

Eligibility Criteria

Inclusion Criteria

• Have a diagnosis of congenital Alpha1-antitrypsin deficiency (AATD) with an allelic combination of ZZ, SZ, Z(null), (null)(null), S(null), or "at-risk" alleles (subjects with "at-risk" alleles must be individually evaluated for eligibility by the Medical Monitor).
• Have a documented pre-Alpha1-Proteinase Inhibitor (PI) augmentation therapy serum alpha-1 antitrypsin (AAT) level <11 micrometer (μM) (80 milligrams per decilitre (mg/dL) if measured by radial immunodiffusion or 50 mg/dL if measured by nephelometry).
• Subjects may be naïve to Alpha1-PI augmentation therapy or may be currently receiving Alpha1-PI augmentation therapy or received Alpha1-PI augmentation therapy within the past. If the subject is currently receiving Alpha1-PI augmentation therapy of any kind, he/she must be willing to discontinue that treatment for at least 25 days prior to the Week 1 (Baseline) Visit and remain off any kind of Alpha1-PI treatment, other than the IPs for this study, while participating in the study.
• At the Screening Visit, have a post-bronchodilator forced expiratory volume (FEV1) ≥30% and <80% of predicted and FEV1/forced vital capacity (FVC) <70% (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II or III).

Exclusion Criteria

• Have had a moderate or severe Chronic obstructive pulmonary disease (COPD) exacerbation during the 4 weeks before the Week 1 (Baseline) Visit.
• Have history of lung or liver transplant.
• Have any lung surgery during the past 2 years (excluding lung biopsy).
• Have severe concomitant disease (example, congestive heart failure, clinically significant pulmonary fibrosis, malignant disease [except for skin cancers other than melanoma], history of acute hypersensitivity pneumonitis reaction, or current chronic hypersensitivity pneumonitis).
• Females who are pregnant, breastfeeding or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (oral, injectable, or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study.
• Have smoked during the past 6 months or a positive urine cotinine test at the Screening Visit that is due to smoking.
• Participate in another Investigational product (IP) study within one month prior to the Week 1 (Baseline) Visit.
• Have history of anaphylaxis or severe systemic response to any plasma-derived Alpha1-PI preparation or other blood product(s).
• Use systemic steroids above a stable dose equivalent to 5 mg/day prednisone (i.e., 10 mg every 2 days) within the 4 weeks prior to the Week 1 (Baseline) Visit. It is recommended to maintain the same dose throughout the study.
• Use systemic or aerosolized antibiotics for a chronic COPD exacerbation within the 4 weeks prior to the Week 1 (Baseline) Visit.
• Have known selective or severe Immunoglobulin A (IgA) deficiency.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UCLA Medical Center

Los Angeles, California, United States

University of Florida

Gainesville, Florida, United States

University of Miami

Miami, Florida, United States

Cleveland Clinic

Cleveland, Ohio, United States

Medical University of South Carolina - Children's Hospital

Charleston, South Carolina, United States

Countries

United States

Other Identifiers

GC2008

Identifier Type: -

Identifier Source: org_study_id