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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 : January 18, 2023
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Tracking Information
First Submitted Date  ICMJE January 20, 2021
First Posted Date  ICMJE January 25, 2021
Last Update Posted Date January 18, 2023
Actual Study Start Date  ICMJE August 13, 2021
Estimated Primary Completion Date February 5, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2023)
  • Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 668 days ]
  • Number of Participants With Suspected Adverse Drug Reactions (ADRs) [ Time Frame: Up to 668 days ]
  • Number of Participants With Infusion Site Reactions [ Time Frame: Up to 668 days ]
  • Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 668 days ]
  • Number of Participants With AEs and SAEs Leading to Discontinuation [ Time Frame: Up to 668 days ]
  • Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations [ Time Frame: Up to 668 days ]
  • Number of Participants With Clinically Significant Abnormalities in Vital Signs (Heart Rate, Blood Pressure, Respiratory Rate, and Temperature) [ Time Frame: Up to 668 days ]
  • Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Up to 668 days ]
  • Change from Baseline in Forced Vital Capacity (FVC) [ Time Frame: Up to 668 days ]
  • Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters (Chemistry, Hematology, Urinalysis) [ Time Frame: Up to 668 days ]
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 20, 2021)
  • Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 252 days ]
  • Number of Participants With Suspected Adverse Drug Reactions (ADRs) [ Time Frame: Up to 252 days ]
  • Number of Participants With Infusion Site Reactions [ Time Frame: Up to 252 days ]
  • Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 252 days ]
  • Number of Participants With AEs and SAEs Leading to Discontinuation [ Time Frame: Up to 252 days ]
  • Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations [ Time Frame: Up to 252 days ]
  • Number of Participants With Clinically Significant Abnormalities in Vital Signs (Heart Rate, Blood Pressure, Respiratory Rate, and Temperature) [ Time Frame: Up to 252 days ]
  • Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Up to 252 days ]
  • Change from Baseline in Forced Vital Capacity (FVC) [ Time Frame: Up to 252 days ]
  • Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters (Chemistry, Hematology, Urinalysis) [ Time Frame: Up to 252 days ]
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Alpha1-Antitrypsin Deficiency
Intervention  ICMJE
  • Biological: Alpha-1 15%
    Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion
  • Biological: Liquid Alpha1-Proteinase Inhibitor (Human)
    Intravenous infusion
    Other Name: Prolastin®-C Liquid
Study Arms  ICMJE
  • 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.
    Intervention: Biological: Alpha-1 15%
  • 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.
    Intervention: Biological: Liquid Alpha1-Proteinase Inhibitor (Human)
  • 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.
    Intervention: Biological: Alpha-1 15%
  • 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.
    Intervention: Biological: Alpha-1 15%
  • 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.
    Intervention: Biological: Liquid Alpha1-Proteinase Inhibitor (Human)
  • 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.
    Intervention: Biological: Alpha-1 15%
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 20, 2021)
16
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 5, 2023
Estimated Primary Completion Date February 5, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rhonda Griffin +1 919 316 6693 rhonda.griffin@grifols.com
Contact: Elsa Mondou +1 919 316 2079 elsa.mondou@grifols.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04722887
Other Study ID Numbers  ICMJE GC2008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Grifols Therapeutics LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Grifols Therapeutics LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Grifols Therapeutics LLC
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP