A clinical trial looking at the safety and effectiveness of a new drug for inhalation, looking to treat Alpha-1 Antitrypsin Deficient Patients with Emphysema.

• Register: EUCTR
• Last refreshed on: 23 February 2015
• Main ID: EUCTR2008-005326-36-SE
• Date of registration: 11/09/2009
• Prospective Registration: Yes
• Primary sponsor: Kamada Limited
• Public title: A clinical trial looking at the safety and effectiveness of a new drug for inhalation, looking to treat 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: 06/10/2011
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005326-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

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

Contacts

• Name: Sponsor
• Affiliation: Kamada Limited

• Name: Sponsor
• Affiliation: Kamada Limited

Key inclusion & exclusion criteria

Inclusion criteria:
For the double-blind period:
1. Diagnosis of emphysema confirmed by CT scan. If a report of past CT scan is not available at site documenting diagnosis then a CT scan is to be performed at screening.
2. Male or female patients at least 18 years of age.
3. Able and willing to sign an informed consent.
4. Patient with record of congenital AAT deficiency of phenotype PiZZ (homozygote) or other rare phenotypes related to AAT deficiency and with AAT serum level lower or equivalent to 11 micromole. For patients receiving IV AAT augmentation therapy the serum AAT level threshold does not apply.
5. FEV1/SVC <70% of predicted value post bronchodilator (SVC is slow VC) and FEV1 < 80% of predicted value post-bronchodilator
6. 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.
7. Ability to comply with completion of electronic diary.
8. Ability to self-administer inhaled AAT using the eFlow device.
9. 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.
10. No significant abnormalities in urinalysis according to the Principal Investigator's judgment, taking into considerations the potential effects of the AAT deficiency.
11. No significant abnormalities in ECG per investigator judgment.
12. Negative for HBsAg and antibodies to HCV, HIV-1.
13. 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.
14. 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.

For the open-label extension period:
1. Patients who have completed the 50-week treatment period in the double-blind study as per the protocol.
2. Patients who have already terminated their participation in the double-blind period prior to the time of implementation of the OL extension period in the protocol, provided that the patient:
a. received study treatment for at least 6 months in the double-blind study
AND
b. did not prematurely discontinue from the study due to lost to follow-up or non-compliance with study requirements.
3. For women of childbearing potential, negative pregnancy test and use of contraceptive methods deemed reliable by the investigator. Women are not considered to be of childbearing potential if they are at least 2 years postmenopausal or surgically sterilized.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1
Exclusion criteria:
For the double-blind period:
1. FEV1 = 80% or FEV1 < 20% of predicted value post-bronchodilator.
2. FEV1/SVC=70%
3. History of lung transplant.
4. Any lung surgery within the past two years.
5. On any thoracic surgery waiting list.
6. End of last exacerbation less than 6 weeks prior to screening/re-screening visit.
7. 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 be possibly included after consultation with the treating physician and the sponsor.
8. Active smoking during the last 12 months from screening date.
9. Pregnancy or lactation.
10. Woman of child-bearing potential not taking adequate contraception deemed reliable by the investigator.
11. 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.
12. Evidence of ongoing viral infection with HCV, HBV and/or HIV.
13. Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally prescribed drugs.
14. IgA Deficiency
15. History of life threatening allergy, anaphylactic reaction, or systemic response to human plasma derived products.
16. Participation in another clinical trial within 30 days prior to baseline visit.
17. Inability to attend scheduled clinic visits and/or comply with the study protocol.
18. Any other factor that, in the opinion of the investigator, would prevent the patient from complying with the requirements of the protocol.

For the open-label extension period:
1. Clinically significant adverse event(s) in the double-blind period or clinically significant intercurrent illness after termination of participation in the doubleblind period that, in the opinion of the investigator, might prevent the patient from safely participating in the OL extension period of the study.
2. A clinically significant deterioration in lung function that, in the opinion in the investigator, might prevent the patient from safely participating in the OL extension period of the study.
3. Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally prescribed drugs.
4. Occurrence of a life threatening allergy, anaphylactic reaction, or systemic response to human plasma derived products.
5. Received lung transplant or underwent lung surgery since termination of participation in the double blind study.
6. Active smoking.
7. Pregnancy or lactation.
8. Women of childbearing potential not taking adequate contraception deemed reliable by the investigator.
9. Participation in another clinical trial since termination of participation in the double-blind period of the study.
10. Any other factor that, in the opinion of the investigator, would prevent the patient from complying with the requirements of the protocol or would jeopardize the safety of the patient.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alpha-1 Antitrypsin deficiency in patients with emphysema.
MedDRA version: 17.0 Level: PT Classification code 10001806 Term: Alpha-1 anti-trypsin deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Aerosolized human Alpha-1 Antitrypsin
Product Code: Kamada-AAT for inhalation
Pharmaceutical Form: Nebuliser solution
CAS Number: 8000047054
Other descriptive name: ALPHA-1-ANTITRYPSIN
Concentration unit: g/l gram(s)/litre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Nebuliser solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): The time from randomization to the first event-based exacerbation with a severity of moderate or severe during the double-blind treatment period. If patients do not have a moderate or severe exacerbation by their last scheduled dose of study drug during the double-blind period, the time to exacerbation will be considered censored on that date. If a patient discontinues from the study prior to Week 50 with no moderate or severe exacerbation, his time to first exacerbation will be censored on the date of his last dose of study drug.

Main Objective: To explore rate and severity of exacerbations in AAT deficient patients when treated with inhaled AAT or placebo during a 50-week double-blind treatment period. The objective will be evaluated by the primary endpoint of the time from randomization to the first exacerbation with a severity of moderate or severe.

Secondary Objective: Secondary objectives in this study are to evaluate the safety profile of inhaled AAT versus placebo and to explore additional parameters that may demonstrate the effect of inhaled AAT on rate and severity of exacerbations in AAT deficient patients during the 50-week double-blind treatment period. In addition, to evaluate the safety, tolerability of inhaled AAT during the 50 weeks open label extension period.

Timepoint(s) of evaluation of this end point: Up to 54 weeks.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to 54 weeks.

Secondary end point(s): 1. Time to first event-based exacerbation with a severity of mild, moderate or severe.
2. Severity of the first event-based exacerbation.
3. Rate of event-based exacerbation episodes. The number of mild, moderate or severe event-based exacerbations per patient during the treatment period.

Secondary ID(s)

2008-005326-36-GB

Kamada-AAT(inhaled)-007

Source(s) of Monetary Support

Kamada Limited