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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Alpha1-Antitrypsin Deficiency
• Intervention / Treatment: Biological: Alpha-1 15%; Biological: Liquid Alpha1-Proteinase Inhibitor (Human)

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Elsa Mondou; Phone Number: +1 919 316 2079; Email: elsa.mondou@grifols.com
• Study Contact Backup: Name: Beatriz Garcia Castro; Phone Number: +(34) 670923669; Email: beatriz.garcia@grifols.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Not yet recruiting
      • Dignity Health-St. Joseph's Hospital & Medical Center
      • Principal Investigator: Rajat Walia, MD
      • Contact: Noor Elkurwi; Phone Number: 602-406-5853; Email: Noor.Elkurwi@commonspirit.org
  • California
    • Los Angeles, California, United States, 90025
      • Not yet recruiting
      • UCLA Medical Center
      • Principal Investigator: Igor Barjaktarevic, MD
      • Contact: Se Yoon; Email: SeYoon@mednet.ucla.edu
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Withdrawn
      • George Washington University
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida
      • Principal Investigator: Jorge Lascano, MD
      • Contact: Jesse West; Email: jesse.west@medicine.ufl.edu
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Principal Investigator: Michael Campos, MD
      • Contact: Jennifer Biondo; Phone Number: 847-541-0094; Email: jnb184@med.miami.edu
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Withdrawn
      • Southeastern Research Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Principal Investigator: Tejwani Vickram, MD
      • Contact: Shauna Jo Hendershot; Email: HENDERS@ccf.org
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina - Children's Hospital
      • Principal Investigator: Charlie Strange, MD
      • Contact: Gwen Hayden; Email: blantonm@musc.edu
  • Texas
    • The Woodlands, Texas, United States, 77380
      • Recruiting
      • Renovatio Clinical
      • Contact: Maya Fleyhan; Email: maya.fleyhan@renovatioclinical.com
      • Principal Investigator: Ather Siddiqi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: Alpha-1 15%; Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion
Experimental: 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.	Biological: Alpha-1 15%; Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion
Experimental: 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.	Biological: Liquid Alpha1-Proteinase Inhibitor (Human); Intravenous infusion; Other Names: Prolastin®-C Liquid
Experimental: 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.	Biological: Liquid Alpha1-Proteinase Inhibitor (Human); Intravenous infusion; Other Names: Prolastin®-C Liquid
Experimental: 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.	Biological: Alpha-1 15%; Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion
Experimental: 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.	Biological: Alpha-1 15%; Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2021
• Primary Completion (Estimated): March 14, 2025
• Study Completion (Estimated): March 14, 2025

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 20, 2021
• First Posted (Actual): January 25, 2021

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Lung Diseases, Obstructive; Pathologic Processes; Alpha-1 Antitrypsin Deficiency; Digestive System Diseases; Lung Diseases; Genetic Diseases, Inborn; Protease Inhibitors; Liver Diseases; Pulmonary Disease, Chronic Obstructive; Emphysema; Pulmonary Emphysema; Molecular Mechanisms of Pharmacological Action; AATD; Alpha-1 PI Deficiency; Alpha-1 Proteinase Inhibitor; Serine Proteinase Inhibitors; Subcutaneous Emphysema; Alpha1-Antitrypsin; Trypsin Inhibitors; Enzyme Inhibition
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Protease Inhibitors; Alpha 1-Antitrypsin
• Other Study ID Numbers: GC2008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No