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

NCT02001688 | Completed Phase 2 Results

• 1 other identifier: Kamada-AAT (inhaled)-006
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

To evaluate different doses of "Kamada-AAT for Inhalation" on the levels of alpha 1-proteinase inhibitor and other analytes in epithelial lining fluid (ELF) and serum and to assess the safety of the treatment in subjects with AAT Deficiency.

Conditions

Alpha-1 Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in the Concentration of Antigenic Alpha-1 Antitrypsin (AAT) in the Lung Epithelial Lining Fluid (ELF)

  Patients underwent bronchoalveolar lavage (BAL) prior to initiation of drug and then again after 3 months. Concentration of AAT in the BAL was measured by an enzyme linked immunosorbent assay (ELISA) specific for the normal form of AAT (piM). Urea was also measured in order to determine the dilution factor of the BAL fluid and calculate the concentration of AAT in the ELF.

  12 weeks from initiation of study drug

• Change From Baseline to 12 Weeks in the Concentration of Functional AAT (Alpha-1 Antitrypsin) in ELF

  ITT population with baseline and 12 week values. Patients underwent bronchoalveolar lavage (BAL) prior to initiation of drug and then again after 3 months. Concentration of AAT in the BAL was measured by an antineutrophil elastase capacity (ANEC) assay. Urea was also measured in order to determine the dilution factor of the BAL fluid and calculate the concentration of AAT in the ELF.

  12 weeks from initiation of study drug

Secondary Outcomes (2)

• Change From Baseline in Levels of M Specific AAT in Plasma (PiM)

  12 weeks from initiation of study drug

• Change From Baseline in AAT-neutrophil Elastase (NE) Complexes in ELF

  12 weeks from initiation of study drug

Study Arms (3)

Kamada-AAT for Inhalation, 80mg

EXPERIMENTAL

Daily inhalation of Kamada-AAT for Inhalation, 80mg

Drug: Kamada-AAT for Inhalation, 80mg

Placebo

PLACEBO COMPARATOR

Placebo administered by inhalation daily

Drug: Placebo

Kamada-AAT for Inhalation, 160mg

EXPERIMENTAL

Daily inhalation of Kamada-AAT for Inhalation, 160mg

Drug: Kamada-AAT for Inhalation, 160mg

Interventions

Kamada-AAT for Inhalation, 80mg DRUG

Kamada-AAT for Inhalation, 80mg

Placebo DRUG

Placebo

Kamada-AAT for Inhalation, 160mg DRUG

Kamada-AAT for Inhalation, 160mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kamada, Ltd.: lead

Study Sites (2)

University of Florida, Pulmonary, Critical Care & Sleep Medicine

Gainesville, Florida, 32610, United States

Location

The University of Texas Health Science Center at Tyler Center for Clinical Research

Tyler, Texas, 75708, United States

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Interventions

Inhalation

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Kamada Ltd

sharonc@kamada.com

+972-72-2219172

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 24, 2013
• First Posted: December 5, 2013
• Study Start: April 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: May 1, 2016
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2019-12

Locations

US (2)