International Study Evaluating the Safety and Efficacy of Inhaled, Human, Alpha-1 Antitrypsin (AAT) in Alpha-1 Antitrypsin Deficient Patients With Emphysema

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Kamada, Ltd.
ClinicalTrials.gov Identifier:
NCT01217671
First received: September 15, 2010
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

This is a randomised , placebo controlled, double blind , multicentre, Phase II/III study evaluating the safety and efficacy of Kamada AAT for inhalation in patients with Emphysema caused by Alpha-1 Antitrypsin (AAT) deficiency.


Condition Intervention Phase
Emphysema
Biological: Kamada AAT for inhalation
Other: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II/III, Double-Blind, Randomized, Placebo-Controlled, Multicenter, International Study Evaluating the Safety and Efficacy of Inhaled, Human, Alpha-1 Antitrypsin (AAT) in Alpha-1 Antitrypsin Deficient Patients With Emphysema

Resource links provided by NLM:


Further study details as provided by Kamada, Ltd.:

Primary Outcome Measures:
  • Exacerbation events and lung density [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse Events [ Time Frame: Approximately 1 year ] [ Designated as safety issue: Yes ]
  • Vital Signs [ Time Frame: Approximately 1 year ] [ Designated as safety issue: Yes ]
  • Physical Examination [ Time Frame: Approximately 1 year ] [ Designated as safety issue: Yes ]
  • ECG [ Time Frame: Approximately 1 year ] [ Designated as safety issue: Yes ]
  • Lung function [ Time Frame: Approximately 1 year ] [ Designated as safety issue: Yes ]
  • Laboratory Evaluations [ Time Frame: Approximately 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 168
Study Start Date: December 2009
Estimated Study Completion Date: December 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alpha-1 Antitrypsin Biological: Kamada AAT for inhalation
Alpha-1 Antitrypsin (AAT)
Other Name: Alpha-1 Proteinase Inhibitor (API)
Placebo Comparator: Placebo Other: Placebo
Placebo

Detailed Description:

Alpha-1 Antitrypsin Deficiency, also called Alpha-1-Proteinase Inhibitor (API) deficiency, is a genetic disorder characterized by the production of an abnormal amount of AAT protein and reduced circulating levels of this protein. Subjects with AAT deficiency are at increased risk for developing Emphysema. It is believed that this is the result of the chronic activity of elastase released by cells continually present in the lungs in low numbers.

Three blinded interim analyses have shown that there are no safety issues and no concerns regarding tolerability.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Principal Inclusion Criteria:

  • Diagnosis of emphysema confirmed by CT scan. If a report of past CT scan is not available at site documenting then a CT scan is to be performed at screening
  • Male or female patients at least 18 years of age.
  • Able and willing to sign an informed consent.
  • Patient with record of congenital AAT deficiency of phenotype PiZZ (homozygote) or other rare phenotypes related to AAT deficiency and with AAT serum level ≤ 11 micromole. For patients receiving IV AAT augmentation therapy the serum AAT level threshold does not apply.
  • FEV1/SVC <70% of predicted value post bronchodilator (SVC is slow VC) and FEV1 < 80% of predicted value post-bronchodilator
  • History of at least two moderate or severe exacerbations that required change in treatment (antibiotics, systemic steroids, hospitalization) in the last 18 months prior to date of screening , with at least one of these occurring within the last 12 months prior to screening.
  • Ability to comply with completion of electronic diary.
  • Ability to self-administer inhaled AAT.
  • No significant abnormalities in serum hematology, serum chemistry and serum inflammatory / immunogenic markers according to the Principal Investigator's judgment, taking into considerations the potential effects of the AAT deficiency.
  • No significant abnormalities in urinalysis according to the Principal Investigator's judgment, taking into considerations the potential effects of the AAT deficiency.
  • No significant abnormalities in ECG per investigator judgment.
  • Negative for HBsAg and for antibodies to HCV, HIV-1.
  • AAT deficient patients who are either naïve (not receiving IV augmentation therapy) or AAT deficient patients (receiving IV augmentation therapy), if they have been stable on regular therapy for at least 3 months prior to the screening visit and are willing to continue the same regime throughout this trial. Note that only sites in Germany can recruit patients who are currently being treated with IV AAT.Patients who stopped IV augmentation treatment 6 months prior to screening date and will not re-start this treatment for the course of the study will be considered Naïve.
  • Non-pregnant, non-lactating female patients, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator, or who are at least 2 years post-menopausal or surgically sterilized.

Principal Exclusion Criteria:

  • FEV1 >= 80% or FEV1 < 20% of predicted value post-bronchodilator.
  • FEV1/SVC>=70%
  • History of lung transplant.
  • Any lung surgery within the past two years.
  • On any thoracic surgery waiting list.
  • End of last exacerbation less than 6 weeks prior to screening/re-screening visit.
  • Clinically significant intercurrent illnesses (except for respiratory or liver disease secondary to AAT deficiency), including: cardiac, hepatic, renal, endocrine, neurological, hematological, neoplastic, immunological, skeletal or other) that in the opinion of the investigator, could interfere with the safety, compliance or other aspects of this study. Patients with well-controlled, chronic diseases could possibly be included after consultation with the treating physician and the sponsor.
  • Active smoking during the last 12 months from screening date.
  • Pregnancy or lactation.
  • Woman of child-bearing potential not taking adequate contraception deemed reliable by the investigator.
  • Presence of psychiatric/ mental disorder or any other medical disorder which might impair the patient's ability to give informed consent or to comply with the requirements of the study protocol.
  • Evidence of ongoing viral infection with HCV, HBV and/or HIV.
  • Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally prescribed drugs.
  • IgA Deficiency
  • History of life threatening allergy, anaphylactic reaction, or systemic response to human plasma derived products.
  • Participation in another clinical trial within 30 days prior to baseline visit.
  • Inability to attend scheduled clinic visits and/or comply with the study protocol.
  • Any other factor that, in the opinion of the investigator, would prevent the patient from complying with the requirements of the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01217671

Locations
Canada
Inspiration Research Limited
Toronto, Canada
Seymour Health Centre
Vancouver, Canada
Denmark
Gentofte Hospital
Hellerup, Denmark
Germany
Universitätsklinikum des Saarlandes
Homburg/Saar, Germany
Universitatsklinikum Gieben und Marburg
Marburg, Germany
Ireland
Beaumont Hospital
Dublin, Ireland
Netherlands
LUMC
Leiden, Netherlands
Sweden
Malmo University Hospital
Malmo, Sweden, 20502
Karolinska Universitetssjukhuset Solna
Stockholm, Sweden
United Kingdom
Queen Elizabeth Hospital
Birmingham, United Kingdom
Royal Infirmary of Edinburgh
Edinburgh, United Kingdom
Royal Brompton Hospital
London, United Kingdom
Sponsors and Collaborators
Kamada, Ltd.
Investigators
Principal Investigator: Jan Stolk, Professor LUMC, Leiden, Netherlands
  More Information

No publications provided

Responsible Party: Kamada, Ltd.
ClinicalTrials.gov Identifier: NCT01217671     History of Changes
Other Study ID Numbers: Kamada-AAT (inhaled) 007
Study First Received: September 15, 2010
Last Updated: July 30, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Denmark: Danish Medicines Agency
Ireland: Irish Medicines Board
Germany: Paul-Ehrlich-Institut
Canada: Health Canada
Sweden: The Medical Products Agency

Keywords provided by Kamada, Ltd.:
Pulmonary, Emphysema
Alpha-1 Antitrypsin Deficiency

Additional relevant MeSH terms:
Emphysema
Pulmonary Emphysema
Pathologic Processes
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Alpha 1-Antitrypsin
Protein C Inhibitor
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014