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

• ClinicalTrials.gov Identifier: NCT04722887
• Recruitment Status: Recruiting
• First Posted: January 25, 2021
• Last Update Posted: January 18, 2023
• Sponsor: Grifols Therapeutics LLC
• Information provided by (Responsible Party): Grifols Therapeutics LLC

Tracking Information

• First Submitted Date: January 20, 2021
• First Posted Date: January 25, 2021
• Last Update Posted Date: January 18, 2023
• Actual Study Start Date: August 13, 2021
• Estimated Primary Completion Date: February 5, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Alpha1-Antitrypsin Deficiency

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 20, 2021): 16
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 5, 2023
• Estimated Primary Completion Date: February 5, 2023 (Final data collection date for primary outcome measure)

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).
• 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

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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: United States

Administrative Information

• NCT Number: NCT04722887
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Grifols Therapeutics LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Grifols Therapeutics LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Grifols Therapeutics LLC
• Verification Date: January 2023