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

NCT01213043 | Completed Phase 2 Results

• 1 other identifier: T6004-201/Version 2
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

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).

Conditions

Emphysema; Alpha 1-antitrypsin Deficiency (AATD)

Keywords

emphysema; alpha 1-antitrypsin; alpha 1-antitrypsin deficiency (AATD); alpha 1-proteinase inhibitor (Alpha-1 PI)

Outcome Measures

Primary Outcomes (9)

• Subjects With Treatment-Emergent Adverse Events (TEAEs)

  Number of subjects experiencing at least one TEAE. TEAEs were defined as any adverse event (AE) during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).

  22 weeks

• Subjects With Drug-Related TEAE(s)

  Number of subjects with at least one TEAE that was determined by the Investigator to be either "possibly related" or "related" to the investigational product (i.e., Prolastin-C).

  22 weeks

• Subjects With Treatment-Emergent Serious Adverse Events (SAEs)

  Number of subjects who experienced at least one treatment-emergent SAE.

  22 weeks

• Subjects Withdrawn Due to an AE(s)

  Number of subjects who were withdrawn from the study due to at least one AE.

  22 weeks

• Subjects With Treatment-Emergent Pulmonary Exacerbation(s)

  Number of subjects with at least one treatment-emergent pulmonary exacerbation

  22 weeks

• Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s)

  Number of subjects who experienced at least one severe TEAE or pulmonary exacerbation.

  22 weeks

• Number of TEAEs

  Total number of TEAEs reported.

  22 Weeks

• Number of Drug-related TEAEs

  Total number of drug-related TEAEs reported

  22 Weeks

• Number of Treatment-Emergent Pulmonary Exacerbations

  Total number of treatment-emergent pulmonary exacerbations.

  22 Weeks

Secondary Outcomes (2)

• AUC0-7days

  Week 8 and Week 18 at the following timepoints: 0 (pre-infusion), completion of first infusion bag, completion of 2nd infusion bag, and 15 min, 30 min, and 1, 2, 4, 8, 24, 48, 120, and 168 hours post-dose

• Mean Trough

  Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19

Study Arms (2)

Prolastin-C, 60 mg/kg

ACTIVE COMPARATOR

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).

Biological: Prolastin-C, 60 mg/kg

Prolastin-C, 120 mg/kg

EXPERIMENTAL

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).

Biological: Prolastin-C, 120 mg/kg

Interventions

Prolastin-C, 60 mg/kg BIOLOGICAL

60 mg/kg weekly infusion of Prolastin-C for 8 weeks

Also known as: Alpha1-Proteinase Inhibitor, Alpha1-Proteinase Inhibitor (Human), Modified Process, Alpha-1 MP

Prolastin-C, 60 mg/kg

Prolastin-C, 120 mg/kg BIOLOGICAL

120 mg/kg weekly infusion of Prolastin-C for 8 weeks

Also known as: Alpha1-Proteinase Inhibitor, Alpha1-Proteinase Inhibitor (Human), Modified Process, Alpha-1 MP

Prolastin-C, 120 mg/kg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (5)

University of Florida College of Medicine

Gainesville, Florida, 32610-0225, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Temple University Hosptial/Temple Lung Center

Philadelphia, Pennsylvania, 19140, United States

Location

Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine

Charleston, South Carolina, 29425-6300, United States

Location

The University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

Related Publications (1)

• Willis T, Wee K, Mohn G. A high-purity Alpha-1 proteinase inhibitor from human plasma, TAL6004. Proceeding of the 19th European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna, Austria. Abstracts;34:S53.

  BACKGROUND

MeSH Terms

Conditions

Emphysema; alpha 1-Antitrypsin Deficiency

Interventions

alpha 1-Antitrypsin; Mp alpha1 receptor

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Results Point of Contact

• Title: Benjamin King, PhD
• Organization: Grifols Therapeutics Inc.

ben.king@grifols.com

Study Officials

• Mark Brantly, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Michael Campos, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Friedrich Kueppers, MD

  Temple University Hospital/Temple Lung Center

  PRINCIPAL INVESTIGATOR

• James Stocks, MD

  The University of Texas Health Science Center at Tyler

  PRINCIPAL INVESTIGATOR

• Charlie Strange, MD

  Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2010
• First Posted: October 1, 2010
• Study Start: November 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: May 20, 2013
• Results First Posted: May 20, 2013

Record last verified: 2013-04

Locations

US (5)