A Study to Assess Safety and PK of Liquid Alpha₁-Proteinase Inhibitor (Human) in Treating Alpha₁-Antitrypsin Deficiency

• ClinicalTrials.gov Identifier: NCT02282527
• Recruitment Status: Completed
• First Posted: November 4, 2014
• Results First Posted: March 13, 2017
• Last Update Posted: March 13, 2017
• Sponsor: Grifols Therapeutics LLC
• Information provided by (Responsible Party): Grifols Therapeutics LLC

Study Description

Brief Summary:

Grifols Therapeutics Inc. conducted a multi-center, randomized, double-blind, crossover study to evaluate the safety, immunogenicity, and pharmacokinetics (PK) of Liquid Alpha₁-PI compared to the currently licensed product, Prolastin-C, in subjects with Alpha₁-Antitrypsin Deficiency (AATD).

Condition or disease	Intervention/treatment	Phase
Alpha₁-Antitrypsin Deficiency	Biological: Liquid Alpha₁-PI; Biological: Prolastin-C	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blind, Crossover Study to Assess the Safety and Pharmacokinetics of Liquid Alpha₁-Proteinase Inhibitor (Human) Compared to Prolastin®-C in Subjects With Alpha₁-Antitrypsin Deficiency
• Study Start Date: October 2014
• Actual Primary Completion Date: January 2016
• Actual Study Completion Date: January 2016

Arms and Interventions

Arm	Intervention/treatment
Treatment Sequence 1; Subjects were treated first with Liquid Alpha₁-PI and then treated with Prolastin-C	Biological: Liquid Alpha₁-PI; Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions; Biological: Prolastin-C; Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions
Treatment Sequence 2; Subjects were treated first with Prolastin-C and then treated with Liquid Alpha₁-PI	Biological: Liquid Alpha₁-PI; Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions; Biological: Prolastin-C; Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions

Outcome Measures

Primary Outcome Measures :

1. AUC(0-7 Days) Based on Antigenic Content [ Time Frame: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose ]
   The primary PK objective of this study was to demonstrate the bioequivalence of Liquid Alpha₁-PI 60 mg/kg to Prolastin-C 60 mg/kg, as measured by AUC from 0 to 7 days (AUC0-7days) using an antigenic content assay of alpha₁-PI, at approximate steady state in subjects with AATD.

Secondary Outcome Measures :

1. AUC(0-7 Days) Based on Functional Activity [ Time Frame: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose ]
   The exploratory PK objective of this study was to demonstrate the bioequivalence of Liquid Alpha₁-PI 60 mg/kg to Prolastin-C 60 mg/kg, as measured by AUC from 0 to 7 days (AUC 0-7 days) using a functional activity assay of alpha₁-PI, at approximate steady state in subjects with AATD.
2. Number of Subjects With Immunogenicity Response [ Time Frame: Weeks 1, 9, 17, and 20 ]
   Blood samples for immunogenicity testing were collected at Weeks 1 (Baseline), 9, 17, and 20. Any samples that tested positive for alpha₁-PI antibodies were tested for neutralizing antibodies and antibody titer. Immunogenicity testing was performed using validated assays in a multitiered approach. Samples collected at Week 1 (Baseline) and at Weeks 9 and 20 were tested for immunogenicity while samples collected at Week 17 were to be tested for immunogenicity only if deemed appropriate (eg, unexpected PK profile).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Be between 18 and 70 years of age, inclusive
• Had a diagnosis of congenital AATD
• Had a documented total alpha₁-PI level < 11 µM. If the total alpha₁-PI level had yet to be documented, a blood draw for total alpha₁-PI level was obtained at the Screening Visit
• Had a post-bronchodilator Forced expiratory volume in 1 second (FEV1) ≥ 30% and < 80% of predicted and FEV1/forced vital capacity (FVC) < 70%
• If the subject had received alpha₁-PI augmentation therapy of any kind, he/she must have been be willing to discontinue that treatment at the Week 1 (Baseline) Visit and remain off any kind of alpha₁-PI treatment, other than the investigational products for this study, while participating in the study

Exclusion Criteria:

• Subject had a moderate or severe pulmonary exacerbation during the 4 weeks before the Week 1 (Baseline) Visit
• History of lung or liver transplant
• Any lung surgery during the past 2 years (excluding lung biopsy)
• Liver cirrhosis confirmed by biopsy
• Elevated liver enzymes (aspartate transaminase [AST], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]) equal to or greater than 2.5 times the upper limit of normal
• Severe concomitant disease (e.g., congestive heart failure, clinically significant pulmonary fibrosis, malignant disease [with the exception of skin cancers other than melanoma], history of acute hypersensitivity pneumonitis reaction, or current chronic hypersensitivity pneumonitis)
• Females who were 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 abstinence) throughout the study
• Known previous infection with or clinical signs and symptoms consistent with current hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
• Smoking during the past 6 months or a positive urine cotinine test at the Screening Visit that is due to smoking
• Participation in another investigational drug study within one month prior to the Week 1 (Baseline) Visit
• History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s)
• Use of 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 inhaled steroids are not considered systemic steroids)
• Use of systemic or aerosolized antibiotics for an exacerbation within the 4 weeks prior to the Week 1 (Baseline) Visit
• Known selective or severe Immunoglobulin A (IgA) deficiency

Contacts and Locations

Locations

United States, Colorado

National Jewish Health

Denver, Colorado, United States, 80206

United States, Florida

University of Florida Gainesville

Gainesville, Florida, United States, 32610

University of Miami - Miller School of Medicine

Miami, Florida, United States, 33136

United States, North Carolina

PMG Research of Wilmington

Wilmington, North Carolina, United States, 28401

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Texas

University of Texas Health Science Center

Tyler, Texas, United States, 75708

Sponsors and Collaborators

Grifols Therapeutics LLC

More Information

• Responsible Party: Grifols Therapeutics LLC
• ClinicalTrials.gov Identifier: NCT02282527
• Other Study ID Numbers: GTI1402
• First Posted: November 4, 2014
• Results First Posted: March 13, 2017
• Last Update Posted: March 13, 2017
• Last Verified: January 2017

Additional relevant MeSH terms:

Alpha 1-Antitrypsin Deficiency; Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Alpha 1-Antitrypsin; Trypsin Inhibitors; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action