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

Alpha1-Antitrypsin Deficiency Clinical Trial

Official title:

A Multi-Center, Single-Dose and Repeat-Dose Over Eight Weeks, Sequential Cohort Study to Evaluate Safety and Tolerability as Well as Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% Administered Subcutaneously in Subjects With Alpha1-Antitrypsin Deficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04722887
• Other study ID #: GC2008
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 13, 2021
• Est. completion date: March 14, 2025

Study information

• Verified date: June 2024
• Source: Grifols Therapeutics LLC
• Contact: Beatriz Garcia Castro
• Phone: +(34) 670923669
• Email: beatriz.garcia[@]grifols.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: March 14, 2025
• Est. primary completion date: March 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Alpha1-Antitrypsin Deficiency

Intervention

Biological:
• Alpha-1 15%
Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion
• Liquid Alpha1-Proteinase Inhibitor (Human)
Intravenous infusion

Locations

Country	Name	City	State
United States	Medical University of South Carolina - Children's Hospital	Charleston	South Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Florida	Gainesville	Florida
United States	UCLA Medical Center	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Dignity Health-St. Joseph's Hospital & Medical Center	Phoenix	Arizona
United States	Renovatio Clinical	The Woodlands	Texas
United States	George Washington University	Washington	District of Columbia
United States	Southeastern Research Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs)		Up to 668 days
Primary	Number of Participants With Suspected Adverse Drug Reactions (ADRs)		Up to 668 days
Primary	Number of Participants With Infusion Site Reactions		Up to 668 days
Primary	Number of Participants With Serious Adverse Events (SAEs)		Up to 668 days
Primary	Number of Participants With AEs and SAEs Leading to Discontinuation		Up to 668 days
Primary	Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations		Up to 668 days
Primary	Number of Participants With Clinically Significant Abnormalities in Vital Signs (Heart Rate, Blood Pressure, Respiratory Rate, and Temperature)		Up to 668 days
Primary	Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1)		Up to 668 days
Primary	Change from Baseline in Forced Vital Capacity (FVC)		Up to 668 days
Primary	Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters (Chemistry, Hematology, Urinalysis)		Up to 668 days
Primary	Immunogenicity: Number of Participants With Alpha1-PI Antibodies		Treatment Period 1- Single-Dose Week 1; Treatment Period 2- Repeat-Dose Weeks 1 and 9