Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency (SPARK)

Grifols

Status and phase: Completed; Phase 2

Conditions: Emphysema; Alpha 1-antitrypsin Deficiency (AATD)

Treatments: Biological: Prolastin-C, 60 mg/kg; Biological: Prolastin-C, 120 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01213043

T6004-201/Version 2

Details and patient eligibility

About

This is a study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C (alpha1-proteinase inhibitor [alpha1-PI] [Human]), compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency (AATD).

Full description

The question of whether higher doses of alpha1-PI (>60 mg/kg) are able to provide better protection to patients with alpha 1-antitrypsin deficiency is currently unknown. As a first step to address this question, the present study has been undertaken. This is a multi-center, randomized, double-blind, crossover study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C, compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency. This study is a crossover design with 2 treatment sequences:

Treatment Sequence 1: 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 1) (total of 16 treatment weeks)

Treatment Sequence 2: 120 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 11) (total of 16 treatment weeks)

Approximately 15 subjects are planned to be entered into each treatment sequence.

At Weeks 8 to 11 and Weeks 18 to 21, a total of 15 serial blood samples for each subject will be drawn for pharmacokinetic analysis. The expected duration of the study subject's participation will be approximately 25 weeks (which includes a 3-Week Screening Phase, 2-Week Washout Period [between different alpha-1 PI treatment doses], and a 4-Week Follow-up Period). The following safety parameters will be assessed: adverse events, pulmonary exacerbations, vital signs, pulmonary function tests, and clinical laboratory tests.

Enrollment: 30 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Be between 18 and 70 years of age
• Have a documented diagnosis of congenital AATD
• Have a post-bronchodilator Forced Expired Volume in 1 second (FEV1) of ≥30% and <80% and FEV1/forced vital capacity (FVC) <70%
• If receiving alpha-1 PI augmentation therapy, be willing to discontinue the treatment for the duration of the study

Exclusion criteria

• Had a moderate or severe pulmonary exacerbation during the 4 weeks before the study
• History of lung or liver transplant
• Any lung surgery during the past 2 years
• Confirmed liver cirrhosis
• Elevated liver enzymes
• Severe concurrent disease
• Females who are pregnant or breast-feeding or unwilling to practice effective contraception during the study
• Infection with hepatitis A, B, or C, human immunodeficiency or parvovirus B19
• Smoking during the past 6 months
• Use of systemic steroids within 4 weeks of the study
• Use of antibiotics for an exacerbation within 4 weeks of the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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30 participants in 2 patient groups

Prolastin-C, 60 mg/kg

Active Comparator group

Description:

60 mg/kg weekly infusion of Prolastin-C for 8 weeks. Subjects were infused with 60 mg/kg Prolastin-C by means of one of two possible treatment sequences: 1) 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg Prolastin-C for 8 weeks, or 2) 120 mg/kg Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (total of 16 weeks).

Treatment:

Biological: Prolastin-C, 60 mg/kg

Prolastin-C, 120 mg/kg

Experimental group

Description:

120 mg/kg weekly infusion of Prolastin-C for 8 weeks. Subjects were infused with 120 mg/kg Prolastin-C by means of one of two possible treatment sequences: 1) 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg Prolastin-C for 8 weeks, or 2) 120 mg/kg Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (total of 16 weeks).

Treatment:

Biological: Prolastin-C, 120 mg/kg