Phase II, Safety and ELF Study of "Kamada-API for Inhalation"

• ClinicalTrials.gov Identifier: NCT02001688
• Recruitment Status: Completed
• First Posted: December 5, 2013
• Last Update Posted: June 15, 2016
• Sponsor: Kamada, Ltd.
• Information provided by (Responsible Party): Kamada, Ltd.

Study Description

Brief Summary:

To evaluate different doses of "Kamada-API 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 Alpha-1 Antitrypsin Deficiency.

Condition or disease	Intervention/treatment	Phase
Alpha-1 Antitrypsin Deficiency	Biological: Kamada-API for Inhalation, 80mg; Drug: Placebo; Biological: Kamada-API for Inhalation, 160mg	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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
• Study Start Date: April 2014
• Actual Primary Completion Date: February 2016
• Actual Study Completion Date: May 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active, group A; Kamada-API for Inhalation, 80mg	Biological: Kamada-API for Inhalation, 80mg
Placebo Comparator: Placebo; Placebo administered by inhalation daily	Drug: Placebo
Experimental: Active, group B; Kamada-API for Inhalation, 160mg	Biological: Kamada-API for Inhalation, 160mg

Outcome Measures

Primary Outcome Measures :

1. Concentration of active AAT (Alpha-1 antitrypsin) in ELF [ Time Frame: 3 months from dosing ]
2. Concentration of antigenic AAT (Alpha-1 antitrypsin) in ELF [ Time Frame: 3 months from dosing ]

Secondary Outcome Measures :

1. Safety and tolerability [ Time Frame: 3 months and 6 months from dosing ]
   Adverse Events, Serious Adverse Events, physical examination, vital signs
2. Concentration of active AAT in plasma [ Time Frame: 3 months from dosing ]
3. ELF inflammatory analytes [ Time Frame: 3 months from dosing ]
   Cytokines and proteases

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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].
• FEV1 (forced expiratory volume at one second) ≥ 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, 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.
• IgA (immunoglobulin A) Deficiency.
• Inability to undergo bronchoscopy.
• Allergy to lidocaine or any other medicines used in the bronchoscopy process
• Exacerbation of COPD (chronic obstructive pulmonary disease) 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 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.

Contacts and Locations

Locations

United States, Florida

University of Florida, Pulmonary, Critical Care & Sleep Medicine

Gainesville, Florida, United States, 32610

United States, Texas

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

Tyler, Texas, United States, 75708

Sponsors and Collaborators

Kamada, Ltd.

More Information

• Responsible Party: Kamada, Ltd.
• ClinicalTrials.gov Identifier: NCT02001688 History of Changes
• Other Study ID Numbers: Kamada-AAT (inhaled)-006
• First Posted: December 5, 2013
• Last Update Posted: June 15, 2016
• Last Verified: June 2016

Additional relevant MeSH terms:

Alpha 1-Antitrypsin Deficiency; Alpha 1-Antitrypsin; Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Trypsin Inhibitors; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action