Clinical trial NCT04722887: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Alpha1-Antitrypsin Deficiency
Keywords: 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
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2021-01-25
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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 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).
* 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).

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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 668 days
measure: Number of Participants With Suspected Adverse Drug Reactions (ADRs)
timeFrame: Up to 668 days
measure: Number of Participants With Infusion Site Reactions
timeFrame: Up to 668 days
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to 668 days
measure: Number of Participants With AEs and SAEs Leading to Discontinuation
timeFrame: Up to 668 days
measure: Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
timeFrame: Up to 668 days
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs (Heart Rate, Blood Pressure, Respiratory Rate, and Temperature)
timeFrame: Up to 668 days
measure: Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Up to 668 days
measure: Change from Baseline in Forced Vital Capacity (FVC)
timeFrame: Up to 668 days
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters (Chemistry, Hematology, Urinalysis)
timeFrame: Up to 668 days
measure: Immunogenicity: Number of Participants With Alpha1-PI Antibodies
timeFrame: Treatment Period 1- Single-Dose Week 1; Treatment Period 2- Repeat-Dose Weeks 1 and 9
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Dignity Health-St. Joseph's Hospital & Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina - Children's Hospital
state: South Carolina
Study officials:
References: