Evaluate Efficacy and Safety of "Kamada-AAT for Inhalation" in Patients With AATD (InnovAATe)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04204252|
Recruitment Status : Recruiting
First Posted : December 18, 2019
Last Update Posted : August 4, 2022
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Alpha 1-Antitrypsin Deficiency||Drug: Alpha 1-Antitrypsin Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||220 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Prospective Phase III Multi-center, Placebo Controlled, Double Blind Study to Evaluate the Efficacy and Safety of "Kamada-AAT for Inhalation" 80 mg Per Day in Adult Patients With Congenital Alpha-1 Antitrypsin Deficiency With Moderate and Severe Airflow Limitation (40% ≤ FEV1 ≤ 80% of Predicted; FEV1/SVC ≤ 70%)|
|Actual Study Start Date :||November 25, 2019|
|Estimated Primary Completion Date :||December 2025|
|Estimated Study Completion Date :||June 2026|
Active Comparator: Inhaled AAT
Daily inhalation of 80 mg/day "Kamada-AAT for Inhalation" for 104 weeks
Drug: Alpha 1-Antitrypsin
Kamada's alpha 1-antitrypsin product given by inhalation using the eFlow® electronic nebulizer manufactured by PARI Pharma GmbH
Other Name: Kamada alpha 1-antitrypsin for inhalation
Placebo Comparator: Placebo
Daily inhalation of a solution of NaCl in phosphate buffer solution with 0.01% TWEEN-80
Preparation of NaCl in phosphate buffer solution with 0.01% TWEEN-80
- FEV1 post bronchodilator [ Time Frame: 104 weeks ]Change from baseline in post bronchodilator FEV1 at 104 weeks
- CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC). [ Time Frame: 104 weeks ]Change from baseline over 104 weeks of treatment in CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC).
- FEV1 % of predicted [ Time Frame: 104 weeks ]Change from baseline over 104 weeks of treatment in FEV1 % of predicted
- FEV1/FVC % [ Time Frame: 104 weeks ]Change from baseline over 104 weeks of treatment in FEV1/FVC %
- Exacerbations [ Time Frame: 104 weeks ]Annual rate of exacerbations by severity and duration
- 6 minute walk test [ Time Frame: 104 weeks ]Change from Baseline in the distance walked in six minutes
- TEAEs [ Time Frame: 130 weeks ]Rate and severity of adverse events during treatment emergent adverse events (TEAEs), adverse events of special interest (AESIs) and serious adverse events (SAEs) during treatment and follow-up period [Safety Outcome]
- PiM [ Time Frame: 130 weeks ]Plasma M-type AAT specific (PiM) levels evaluated as function of exposure time, antibody response (positive vs. negative), and antibody titers
- ADA/nADA [ Time Frame: 130 weeks ]Rate and titers of binding and neutralizing AAT antibodies (ADA/nADA) in plasma [Safety Outcome]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 65 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Diagnosis of severe AAT deficiency, i.e. patients with either Pi(ZZ), Pi(Z/Null), or Pi(Null/Null) genotypes confirmed by genotype blood test documented prior to screening.
- Serum AAT levels ≤ 11 µM at screening.
- Lung disease with clinical evidence of airflow limitation (post bronchodilator FEV1/SVC ≤ 70%) at screening.
- 40% ≤ FEV1 ≤ 80% of predicted post-bronchodilator at screening.
- Patients who are either naïve or washed out of any AAT treatment for at least 8 weeks prior to randomization.
- Age between 18 to 65 years inclusive at screening.
- Able to read and sign informed consent and willing to participate in the study.
- Males or non-pregnant, non-lactating females whose screening pregnancy test is negative, who are using contraceptive methods deemed reliable by the investigator, who are post-menopausal, or are surgically sterilized.
- High compliance during run in defined as study medication use and e-Diary compliance for at least 20 out of the 28 days of run in.
- Immunoglobulin A (IgA) absolute deficiency defined as serum IgA levels < 0.05 g/L at screening.
- History of life-threatening transfusion reaction(s), allergy, anaphylactic reaction, or systemic response to human plasma-derived products.
- Two or more moderate or any severe exacerbation(s) within the year prior to the baseline visit.
- A moderate exacerbation within 6 weeks prior to the baseline.
- Use of oral or parenteral glucocorticoids in doses above 10 mg of prednisone daily or equivalent generics (substance and dose).
- Clinically significant inter-current illnesses (except for respiratory or liver disease secondary to AAT deficiency), including: cardiac, hepatic, renal, endocrine, neurological, hematological, neoplastic, immunological, skeletal, or other. Patients might be included after consultation with the treating physician and the sponsor if, in the opinion of the Investigator, their condition will not interfere with the safety, compliance or other aspects of this study.
- Hospitalization for any cause 6 weeks prior to screening.
- History of lung or liver transplant.
- On any thoracic or hepatic surgery waiting list.
- Any lung surgery within the past two years (including bronchoscopic lung volume reduction).
- Any smoking within the year prior to screening.
- Evidence of alcohol abuse or history of alcohol abuse, or use of illegal drugs and/or abuse of legally prescribed drugs in the last 5 years prior to screening.
- Acute or chronic hepatitis (hepatitis A, hepatitis B, hepatitis C), or positive human immunodeficiency virus (HIV) serology.
- Signs of significant abnormalities in serum hematology, serum chemistry, serum inflammatory / immunogenic markers and urinalysis per investigator judgment, taking into considerations the potential effects of the AAT deficiency.
- Signs of significant abnormalities in ECG per investigator judgment at screening.
- Presence of psychiatric/ mental disorder or any other medical disorder that might impair the patient's ability to give informed consent or to comply with the requirements of the study protocol. If, in the opinion of the Investigator, the condition will not interfere with the compliance or other aspects of this study, the patient might be included after consultation with the treating physician and the sponsor.
- Participation in another clinical trial involving investigational medication or interventional treatment within 30 days and/or last dose 5 half-lives prior to screening visit.
- Inability to attend scheduled clinic visits and/or comply with study protocol.
- Any other factor that, in the opinion of the investigator, would prevent the patient from complying with the requirements of the protocol.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04204252
|Leiden University Medical Center (LUMC)||Recruiting|
|Leiden, ZA, Netherlands, 2333|
|Contact: Prof. Jan Stolk, MD PhD +31 71 526 5731 firstname.lastname@example.org|
|Principal Investigator:||Jan Stolk, Prof||LUMC|
|Responsible Party:||Kamada, Ltd.|
|Other Study ID Numbers:||
Kamada-AAT (inhaled) 008
|First Posted:||December 18, 2019 Key Record Dates|
|Last Update Posted:||August 4, 2022|
|Last Verified:||August 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Inhaled Alpha 1-Antitrypsin Nebulizer
Alpha 1-Antitrypsin Deficiency
Respiratory Tract Diseases
Digestive System Diseases
Genetic Diseases, Inborn
Protein C Inhibitor
Serine Proteinase Inhibitors
Molecular Mechanisms of Pharmacological Action