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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01217671
• Date of registration: 15/09/2010
• Prospective Registration: No
• Primary sponsor: Kamada, Ltd.
• Public title: International Study Evaluating the Safety and Efficacy of Inhaled, Human, Alpha-1 Antitrypsin (AAT) in Alpha-1 Antitrypsin Deficient Patients With Emphysema
• Scientific 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
• Date of first enrolment: December 2009
• Target sample size: 168
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01217671
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2/Phase 3

Countries of recruitment

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

Contacts

• Name: Jan Stolk, Professor
• Affiliation: LUMC, Leiden, Netherlands

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Emphysema

Intervention(s)

Other: Placebo

Biological: Kamada AAT for inhalation

Primary Outcome(s)

Exacerbation events and lung density [Time Frame: Approximately 1 year]

Secondary Outcome(s)

Adverse Events [Time Frame: Approximately 1 year]

ECG [Time Frame: Approximately 1 year]

Laboratory Evaluations [Time Frame: Approximately 1 year]

Vital Signs [Time Frame: Approximately 1 year]

Lung function [Time Frame: Approximately 1 year]

Physical Examination [Time Frame: Approximately 1 year]

Secondary ID(s)

Kamada-AAT (inhaled) 007

Source(s) of Monetary Support

Please refer to primary and secondary sponsors