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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

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ClinicalTrials.gov Identifier: NCT04722887
Recruitment Status : Recruiting
First Posted : January 25, 2021
Last Update Posted : February 27, 2023
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Study Description
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Brief Summary:
The purpose of this study is to evaluate the safety and tolerability of 72 milligrams per kilogram (mg/kg) and 144 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).

Condition or disease Intervention/treatment Phase
Alpha1-Antitrypsin Deficiency Biological: Alpha-1 15% Biological: Liquid Alpha1-Proteinase Inhibitor (Human) Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 13, 2021
Estimated Primary Completion Date : March 25, 2024
Estimated Study Completion Date : March 25, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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: 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 20, 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 Name: Prolastin®-C Liquid
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 2: Treatment Period 1 (Alpha-1 15%, 144 mg/kg)
Participants will receive Alpha-1 15% 144 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: 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 20, 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 Name: Prolastin®-C Liquid
Experimental: Cohort 2: Treatment Period 2 (Alpha-1 15%, 144 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% 144 mg/kg, for 8 weekly SC infusions.
 Biological: Alpha-1 15%
Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion


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

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
  • Currently receiving Alpha1-PI augmentation therapy or has 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.

Note: Subjects must not be naïve to Alpha1-PI augmentation therapy for study participation.

- 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04722887


Contacts
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Contact: Rhonda Griffin +1 919 316 6693 rhonda.griffin@grifols.com
Contact: Elsa Mondou +1 919 316 2079 elsa.mondou@grifols.com

Locations
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United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Jesse West       jesse.west@medicine.ufl.edu   
Principal Investigator: Jorge Lascano, MD         
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Patricia Graham       PGraham1@med.miami.ed   
Principal Investigator: Michael Campos         
United States, North Carolina
Southeastern Research Center Recruiting
Winston-Salem, North Carolina, United States, 27103
Contact: Karen McCutcheon       kmccutcheon@southeasternresearchcenter.com   
Principal Investigator: Jason Thomason, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Erica Corrao    216-444-0843    CORRAOE2@ccf.org   
Principal Investigator: Tejwani Vickram         
United States, South Carolina
Medical University of South Carolina - Children's Hospital Recruiting
Charleston, South Carolina, United States, 29425
Contact: Gwen Hayden       blantonm@musc.edu   
Principal Investigator: Charlie Strange, MD         
United States, Texas
Renovatio Clinical Recruiting
The Woodlands, Texas, United States, 77380
Contact: Maya Fleyhan       maya.fleyhan@renovatioclinical.com   
Principal Investigator: Ather Siddiqi, MD         
Sponsors and Collaborators
Grifols Therapeutics LLC
More Information
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Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT04722887    
Other Study ID Numbers: GC2008
First Posted: January 25, 2021    Key Record Dates
Last Update Posted: February 27, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Grifols Therapeutics LLC:
Pulmonary Emphysema
Alpha-1 Antitrypsin Deficiency
AATD
Alpha-1 PI Deficiency
Alpha-1 Proteinase Inhibitor
Emphysema
Pathologic Processes
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
 Liver Diseases
Digestive System Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Alpha1-Antitrypsin
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibition
Molecular Mechanisms of Pharmacological Action
Additional relevant MeSH terms:
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Alpha 1-Antitrypsin Deficiency
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
 Pathologic Processes
Protease Inhibitors
Alpha 1-Antitrypsin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors
Serine Proteinase Inhibitors