Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01217671
Other study ID # Kamada-AAT (inhaled) 007
Secondary ID
Status Completed
Phase Phase 2/Phase 3
First received
Last updated
Start date December 2009
Est. completion date June 2015

Study information

Verified date April 2016
Source Kamada, Ltd.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 168
Est. completion date June 2015
Est. primary completion date November 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Kamada AAT for inhalation
Alpha-1 Antitrypsin (AAT)
Other:
Placebo
Placebo

Locations

Country Name City State
Canada Inspiration Research Limited Toronto
Canada Seymour Health Centre Vancouver
Denmark Gentofte Hospital Hellerup
Germany Universitätsklinikum des Saarlandes Homburg/Saar
Germany Universitatsklinikum Gieben und Marburg Marburg
Ireland Beaumont Hospital Dublin
Netherlands LUMC Leiden
Sweden Malmo University Hospital Malmo
Sweden Karolinska Universitetssjukhuset Solna Stockholm
United Kingdom Queen Elizabeth Hospital Birmingham
United Kingdom Royal Infirmary of Edinburgh Edinburgh
United Kingdom Royal Brompton Hospital London

Sponsors (1)

Lead Sponsor Collaborator
Kamada, Ltd.

Countries where clinical trial is conducted

Canada,  Denmark,  Germany,  Ireland,  Netherlands,  Sweden,  United Kingdom, 

References & 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 a1-antitrypsin in patients with severe a1-antitrypsin deficiency and frequent exac — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Exacerbation events and lung density Approximately 1 year
Secondary Adverse Events Approximately 1 year
Secondary Vital Signs Approximately 1 year
Secondary Physical Examination Approximately 1 year
Secondary ECG Approximately 1 year
Secondary Lung function Approximately 1 year
Secondary Laboratory Evaluations Approximately 1 year
See also
  Status Clinical Trial Phase
Recruiting NCT05825261 - Exploring Novel Biomarkers for Emphysema Detection
Completed NCT02914340 - REACH SVS Control Patient Cross-Over Study N/A
Completed NCT02999685 - Home-based Health Management of Chronic Obstructive Lung Disease (COPD) Patients N/A
Completed NCT02238327 - Longitudinal Evaluation of HIV-associated Lung Disease Phenotypes
Completed NCT02232841 - Electrical Impedance Imaging of Patients on Mechanical Ventilation N/A
Completed NCT01615484 - Ex-vivo Perfusion and Ventilation of Lungs Recovered From Non-Heart-Beating Donors to Assess Transplant Suitability N/A
Withdrawn NCT01908933 - Study of the AeriSeal System Treatment in Patients With Advanced Non-Upper Lobe Predominant Heterogeneous Emphysema Phase 3
Completed NCT01476995 - Prognostic Indicators as Provided by the EPIC ClearView N/A
Completed NCT01710449 - Evaluation of Regional Ventilation Using 19F MRI of Inert Perfluorinated Gases Mixed With Oxygen Phase 1
Completed NCT00475007 - Clinical Trial to Evaluate the Safety and Effectiveness of the IBV® Valve System for the Treatment of Severe Emphysema N/A
Suspended NCT00523094 - Vibration Response Imaging (VRI) in Patients That Are Candidates for Undergoing Pulmonary Operation Procedure N/A
Recruiting NCT00129350 - Assessment of Heart and Heart-Lung Transplant Patient Outcomes Following Pulmonary Rehabilitation Phase 1
Completed NCT01953523 - Safety and Clinical Outcomes Study: SVF Deployment for Orthopedic, Neurologic, Urologic, and Cardio-pulmonary Conditions N/A
Completed NCT00000621 - Feasibility of Retinoic Acid Treatment in Emphysema (FORTE) Phase 2
Completed NCT00005292 - Alpha1-antitrypsin Deficiency Registry N/A
Recruiting NCT04537182 - Surgical Compared to Bronchoscopic Lung Volume Reduction in Patients With Severe Emphysema N/A
Active, not recruiting NCT02713347 - Advancing Symptom Alleviation With Palliative Treatment N/A
Recruiting NCT04302272 - STRIVE Post-Market Registry Study
Completed NCT04435327 - Lung Damage Caused by SARS-CoV-2 Pneumonia (COVID-19)
Completed NCT03636347 - A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD With Alvelestat (MPH966) or Placebo. Phase 2

External Links