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

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).
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Number of Participants With Adverse Events (AEs)

Condition

Alpha1-Antitrypsin Deficiency

Intervention

Alpha-1 15%

Study Arms / Comparison Groups

 Cohort 1: Treatment Period 1 (Alpha-1 15%, 72 mg/kg)

Description:  Participants will receive Alpha-1 15% 72 mg/kg, single weekly subcutaneous (SC) infusion in treatment-period 1 (Single-Dose) at Week 1.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

16

Start Date

August 13, 2021

Completion Date

February 5, 2023

Primary Completion Date

February 5, 2023

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
             at 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.
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

, +1 919 316 6693, [email protected]

Location Countries

United States

Location Countries

United States

NCT ID

NCT04722887

Organization ID

GC2008

Responsible Party

Sponsor

Study Sponsor

Grifols Therapeutics LLC

Study Sponsor

, , 

Verification Date

January 2022