Phase II, Safety and Efficacy Study of Kamada-alpha-1-antitrypsin (AAT) for Inhalation"

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02001688
• Date of registration: 24/11/2013
• Prospective Registration: Yes
• Primary sponsor: Kamada, Ltd.
• Public title: Phase II, Safety and Efficacy Study of Kamada-alpha-1-antitrypsin (AAT) for Inhalation"
• Scientific title: Phase II, Double-Blind, Placebo-Controlled Study to Explore the ELF and Plasma Concentration as Well as Safety of Inhaled Alpha-1 Antitrypsin in Alpha-1 Antitrypsin Deficiency Subjects
• Date of first enrolment: April 2014
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02001688
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female patients between 18 and 65 years of age (inclusive).

- Able and willing to sign informed consent.

- Males, and non-pregnant, non-lactating females whose screening pregnancy test is
negative and who are using contraceptive methods deemed reliable by the investigator
or who are post-menopausal or surgically sterilized.

- Diagnosis of alpha1-antitrypsin deficiency [only individuals with a ZZ or Z null
classification].

- Forced expiratory volume in one second (FEV1) = 50% of predicted post bronchodilator

- No respiratory exacerbations within 6 weeks of baseline. Subjects can be re-screened
if exacerbations exist at the time of enrollment.

- No signs of chronic and/or acute Hepatitis A, Hepatitis B, Hepatitis C, HIV infection
and Parvovirus B19, by NAT (for Parvovirus B19, nucleic acid testing (NAT) result must
be < 10^4 IU/mL).

- No significant abnormalities in serum hematology, serum chemistry, serum inflammatory
/ immunogenic markers and urinalysis.

- No significant abnormalities in ECG.

- Not on intravenous augmentation therapy for at least 8 weeks prior to initial dosing
with study drug/placebo and willing to forego intravenous augmentation therapy for the
duration of the study.

Exclusion Criteria:

- 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.

- History of life threatening allergy, anaphylactic reaction, or systemic response to
human plasma derived products.

- History of life threatening transfusion reactions.

- History of lung transplant.

- Current or previous (up to 8 weeks from baseline) use of AAT augmentation therapy or
by any other route

- Current use of oral or parenteral glucocorticoids in doses exceeding 10mg of
prednisone daily or equivalent generics (substance and dose).

- Any lung surgery within the past two years.

- On any thoracic surgery waiting list.

- 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 alcohol abuse or history of alcohol abuse or illegal and/or legally
prescribed drugs.

- Immunoglobulin A (IgA) Deficiency.

- Inability to undergo bronchoscopy.

- Allergy to lidocaine or any other medicines used in the bronchoscopy process

- Exacerbation of chronic obstructive pulmonary disease (COPD) in the previous 6 weeks.

- Participation in another clinical trial involving investigational medication or
interventional treatment within 30 days prior to baseline visit.

- Participation in observational clinical trial which involves any invasive procedure
scheduled to occur during the AAT inhaled study period. If participating in an
observational clinical trial that already completed all diagnostic procedures (e.g.
liver biopsy), any adverse events (AEs) experienced must have returned to baseline
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
form complying with the requirements of the protocol.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alpha-1 Antitrypsin Deficiency

Intervention(s)

Drug: Placebo

Drug: Kamada-AAT for Inhalation, 80mg

Drug: Kamada-AAT for Inhalation, 160mg

Primary Outcome(s)

Change From Baseline to 12 Weeks in the Concentration of Functional AAT (Alpha-1 Antitrypsin) in ELF [Time Frame: 12 weeks from initiation of study drug]

Change From Baseline in the Concentration of Antigenic Alpha-1 Antitrypsin (AAT) in the Lung Epithelial Lining Fluid (ELF) [Time Frame: 12 weeks from initiation of study drug]

Secondary Outcome(s)

Change From Baseline in AAT-neutrophil Elastase (NE) Complexes in ELF [Time Frame: 12 weeks from initiation of study drug]

Change From Baseline in Levels of M Specific AAT in Plasma (PiM) [Time Frame: 12 weeks from initiation of study drug]

Secondary ID(s)

Kamada-AAT (inhaled)-006

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/01/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02001688