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

NCT01217671 | Completed Phase 2 DMC

• 1 other identifier: Kamada-AAT (inhaled) 007
• Study Type: interventional
• Target: 168
• Locations: 7 countries
• Sites: 12

Brief Summary

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.

Conditions

Emphysema

Keywords

Pulmonary, Emphysema; Alpha-1 Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

• Exacerbation events and lung density

  Approximately 1 year

Secondary Outcomes (6)

• Adverse Events

  Approximately 1 year

• Vital Signs

  Approximately 1 year

• Physical Examination

  Approximately 1 year

• ECG

  Approximately 1 year

• Lung function

  Approximately 1 year

Study Arms (2)

Alpha-1 Antitrypsin

EXPERIMENTAL

Biological: Kamada AAT for inhalation

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Kamada AAT for inhalation BIOLOGICAL

Alpha-1 Antitrypsin (AAT)

Also known as: Alpha-1 Proteinase Inhibitor (API)

Alpha-1 Antitrypsin

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kamada, Ltd.: lead

Study Sites (12)

Inspiration Research Limited

Toronto, Canada

Location

Seymour Health Centre

Vancouver, Canada

Location

Gentofte Hospital

Hellerup, Denmark

Location

Universitätsklinikum des Saarlandes

Homburg/Saar, Germany

Location

Universitatsklinikum Gieben und Marburg

Marburg, Germany

Location

Beaumont Hospital

Dublin, Ireland

Location

LUMC

Leiden, Netherlands

Location

Malmo University Hospital

Malmo, 20502, Sweden

Location

Karolinska Universitetssjukhuset Solna

Stockholm, Sweden

Location

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom

Location

Royal Brompton Hospital

London, United Kingdom

Location

Related Publications (1)

• Stolk J, Tov N, Chapman KR, Fernandez P, MacNee W, Hopkinson NS, Piitulainen E, Seersholm N, Vogelmeier CF, Bals R, McElvaney G, Stockley RA. Efficacy and safety of inhaled alpha1-antitrypsin in patients with severe alpha1-antitrypsin deficiency and frequent exacerbations of COPD. Eur Respir J. 2019 Nov 21;54(5):1900673. doi: 10.1183/13993003.00673-2019. Print 2019 Nov.

  PMID: 31467115 RESULT

Related Links

• PubMed

MeSH Terms

Conditions

Emphysema; alpha 1-Antitrypsin Deficiency

Interventions

Inhalation; alpha 1-Antitrypsin

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)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Study Officials

• Jan Stolk, Professor

  LUMC, Leiden, Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 15, 2010
• First Posted: October 8, 2010
• Study Start: December 1, 2009
• Primary Completion: November 1, 2014
• Study Completion: June 1, 2015
• Last Updated: November 29, 2019

Record last verified: 2016-04

Locations

DK (1); IE (1); NL (1); SE (2); GB (3); DE (2); CA (2)