Alpha-1 Antitrypsin DeficiencyPhase 2NCT02001688
Phase II, Safety and Efficacy Study of Kamada-alpha-1-antitrypsin (AAT) for Inhalation"
A Phase 2 study testing Kamada-AAT for Inhalation, 80mg and Kamada-AAT for Inhalation, 160mg in people with Alpha-1 Antitrypsin Deficiency, run by Kamada, Ltd. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alpha-1 Antitrypsin Deficiency
- What is being tested?
- Kamada-AAT for Inhalation, 80mg and Kamada-AAT for Inhalation, 160mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2014to May 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida, Pulmonary, Critical Care & Sleep Medicine
Gainesville, Florida, 32610
The University of Texas Health Science Center at Tyler Center for Clinical Research
Tyler, Texas, 75708
About this study
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
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
- Being tested
- Kamada-AAT for Inhalation, 80mg, Placebo, Kamada-AAT for Inhalation, 160mg
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kamada-AAT for Inhalation, 80mgDrug
PlaceboDrug
Kamada-AAT for Inhalation, 160mgDrug
| Study group | Role | What they receive |
|---|---|---|
| Kamada-AAT for Inhalation, 80mg | Experimental | Daily inhalation of Kamada-AAT for Inhalation, 80mg Receives: Drug: Kamada-AAT for Inhalation, 80mg |
| Placebo | Placebo comparator | Placebo administered by inhalation daily Receives: Drug: Placebo |
| Kamada-AAT for Inhalation, 160mg | Experimental | Daily inhalation of Kamada-AAT for Inhalation, 160mg Receives: Drug: Kamada-AAT for Inhalation, 160mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 weeks from initiation of study drug
Secondary outcomes (2)
Change From Baseline in Levels of M Specific AAT in Plasma (PiM)
Intention to treat (ITT) population with baseline and 12 week values.The median change from baseline to Week 12 in the levels of M-specific AAT (piM) in plasma was measured using a specific ELISA assay for M-specific AAT (piM)
Measured: 12 weeks from initiation of study drug
Change From Baseline in AAT-neutrophil Elastase (NE) Complexes in ELF
Patients underwent a BAL procedure at baseline and 12 weeks and the fluid was analyzed to calculate the change from baseline in the concentration of complexes between AAT and neutrophil elastase in the ELF
Measured: 12 weeks from initiation of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2013 (estimated)
- Study startApr 2014
- Primary completionFeb 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alpha-1 Antitrypsin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kamada, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02001688
- Sponsor's protocol ID
- Kamada-AAT (inhaled)-006
- Status last verified
- Dec 2019
- First submitted
- 24 Nov 2013
- Last updated
- 18 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02001688
- Acronym / sponsor ID
- Kamada-AAT (inhaled)-006
- Conditions
- Alpha-1 Antitrypsin Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Kamada, Ltd.Industry (pharma, biotech, devices)
- Study start
- Apr 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 5 Dec 2013 (estimated)
- Results
- Posted 18 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Kamada-AAT for Inhalation, 80mg | Experimental | Drug: Kamada-AAT for Inhalation, 80mgDaily inhalation of Kamada-AAT for Inhalation, 80mg |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo administered by inhalation daily |
| Kamada-AAT for Inhalation, 160mg | Experimental | Drug: Kamada-AAT for Inhalation, 160mgDaily inhalation of Kamada-AAT for Inhalation, 160mg |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
Primary outcome
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
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.
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
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.
2 secondary outcomes
Change From Baseline in Levels of M Specific AAT in Plasma (PiM)
Time frame: 12 weeks from initiation of study drug
Change From Baseline in AAT-neutrophil Elastase (NE) Complexes in ELF
Time frame: 12 weeks from initiation of study drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Kamada-AAT for Inhalation, 80mg and Kamada-AAT for Inhalation, 160mg in people with Alpha-1 Antitrypsin Deficiency, run by Kamada, Ltd. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.