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Obstructive Lung Diseases |

Safety and Tolerability of 120 mg/kg Dose of Alpha1-Proteinase Inhibitor in Alpha-1 Antitrypsin Deficiency: A Multicenter, Randomized, Double-Blind, Crossover Study

Michael Campos, MD; Mark Brantly*, MD; Junlian Chen, PhD; Rhonda Griffin, BSN; Friedrich Kueppers, MD; James Stocks, MD; Charlie Strange, MD
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University of Miami School of Medicine, Miami, FL


Chest. 2012;142(4_MeetingAbstracts):742A. doi:10.1378/chest.1389856
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Abstract

SESSION TYPE: COPD: Therapeutic Options

PRESENTED ON: Sunday, October 21, 2012 at 10:30 AM - 11:45 AM

PURPOSE: Augmentation therapy with 60 mg/kg intravenous (IV) alpha1-proteinase inhibitor (A1PI) has previously demonstrated a trough serum level of 11 μM in individuals with alpha-1 antitrypsin deficiency (AATD). However, patients treated with weekly 60 mg/kg dose still have lower A1PI levels compared to non-AAT deficient subjects. The safety and tolerability of weekly infusions of 120 mg/kg dose of A1PI in comparison with 60 mg/kg dose in patients with AATD was assessed.

METHODS: Thirty adult subjects with AATD and COPD (28 PIZZ, 1 PIZ (Null), and 1 PIZ with an “at risk” allele); (4 naïve and 26 non-naive), were randomized to receive 60 or 120 mg/kg of Prolastin-C by weekly IV infusion for 8 weeks, followed by a crossover to the alternate dose for 8 weeks. Safety assessments included adverse events (AEs), pulmonary exacerbations (PEx), vital signs, FEV1, FVC and laboratory evaluations.

RESULTS: Twenty-one subjects (70%) in the 60mg/kg group experienced 60 AEs and 14 subjects (46.7%) in the 120mg/kg group experienced 37 AEs. Nine PEx occurred in 7 subjects (23.3%) of the 60mg/kg group and 6 PEx occurred in 5 subjects (16.7%) in the 120mg/kg group, none severe. The most frequent AEs were PEx in both the 60 mg/kg and 120 mg/kg treatment group. Five drug-related AEs occurred in 3 (10%) subjects in the 60mg/kg group and 1 drug-related AE occurred in 1 (3.3%) subject in the 120mg/kg group. No serious AEs occurred during the treatment phase and no subjects discontinued. All immunogenicity test results were negative. There were no safety concerns regarding laboratory assessments, FEV1, FVC or vital signs.

CONCLUSIONS: A higher dose of 120 mg/kg Prolastin-C was safe and well tolerated in subjects with AATD.

CLINICAL IMPLICATIONS: 120 mg/kg doses of Prolastin-C is safe and well tolerated in AATD patients. This higher dose might be more effective at slowing emphysema progression or preventing pulmonary exacerbations in AATD and should be investigated further.

DISCLOSURE: Mark Brantly: University grant monies: The University has a genetic testing agreement with Grifols. Dr. Brantly receives no direct funds from this agreement.

Junlian Chen: Employee: Junliang Chen is an employee of Grifols Therapeutics Inc

Rhonda Griffin: Employee: Employee of Grifols Therapeutics, Inc

The following authors have nothing to disclose: Michael Campos, Friedrich Kueppers, James Stocks, Charlie Strange

No Product/Research Disclosure Information

University of Miami School of Medicine, Miami, FL

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