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

Who is this study for? Patients with Alpha1-Antitrypsin Deficiency
Status: Completed
Location: See all (5) locations...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

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).

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 80
Healthy Volunteers: f
View:

• 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).

Locations
United States
California
UCLA Medical Center
Los Angeles
Florida
University of Florida
Gainesville
University of Miami
Miami
Ohio
Cleveland Clinic
Cleveland
South Carolina
Medical University of South Carolina - Children's Hospital
Charleston
Time Frame
Start Date: 2021-08-13
Completion Date: 2025-08-01
Participants
Target number of participants: 17
Treatments
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.
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.
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.
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.
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.
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.
Authors
Sponsors
Leads: Grifols Therapeutics LLC

This content was sourced from clinicaltrials.gov

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