2024-516054-21-00招募中3 期
A Prospective Phase III Multi-center, 2-Year 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%), Followed by a 2-Year Open- Label Extension
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Kamada Ltd.
- 入组人数
- 108
- 试验地点
- 6
- 主要终点
- FEV1 (L) post bronchodilator change from baseline at 104 weeks.
研究概览
简要总结
To assess the efficacy of Kamada-AAT for Inhalation administered at a dose of 80 mg daily vs. placebo, with efficacy measured by FEV1 post bronchodilator change from baseline at 104 weeks.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Open-Label Extention
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Double-Blind Period: Diagnosis of severe AAT deficiency, i.e. patients with either Pi(ZZ), Pi(Z/Null), or Pi(Null/Null) genotypes.
- •Double-Blind Period: Demonstrated ability to complete eDiary for at least 20 out of the first 28 days of run-in.
- •Open-Label Period: Patients who completed 104 weeks of DB study treatment and attended the end of treatment visit.
- •Open-Label Period: Patients who completed the DB period and attended follow-up visits are eligible for the OLE provided that they comply with all other OLE eligibility criteria.
- •Open-Label Period: Consenting to continue study participation in the OLE phase.
- •Open-Label Period: Agree to continue using contraceptive methods deemed reliable by the investigator for an additional 2 years, unless post‐menopausal or surgically sterilized.
- •Double-Blind Period: Serum AAT levels ≤ 11 μM at screening.
- •Double-Blind Period: Lung disease with clinical evidence of airflow limitation (post bronchodilator FEV1/SVC≤70%) at screening.
- •Double-Blind Period: 40% ≤ FEV1 ≤ 80% of predicted post-bronchodilator at screening.
- •Double-Blind Period: Patients who are either naïve or washed out of any AAT treatment for at least 8 weeks prior to randomization.
- •Double-Blind Period: Age between 18 to 65 years inclusive at screening.
- •Double-Blind Period: Able to read and sign informed consent and willing to participate in the study.
- •Double-Blind Period: 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.
- •Double-Blind Period: Study medication use for at least 20 out of the 28 days of run-in, as recorded in the study nebulization PARI Track data.
排除标准
- •Double-Blind Period: Immunoglobulin A (IgA) absolute deficiency defined as serum IgA levels<0.05 g/L at screening.
- •Double-Blind Period: Any lung surgery within the past two years (including bronchoscopic lung volume reduction).
- •Double-Blind Period: Any smoking within the year prior to screening.
- •Double-Blind Period: 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.
- •Double-Blind Period: Acute or chronic hepatitis (hepatitis A, hepatitis B, hepatitis C,) or positive human immunodeficiency virus (HIV) serology.
- •Double-Blind Period: 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.
- •Double-Blind Period: Signs of significant abnormalities in ECG per investigator judgment at screening.
- •Double-Blind Period: 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.
- •Double-Blind Period: 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.
- •Double-Blind Period: Inability to attend scheduled clinic visits and/or comply with study protocol.
- •Double-Blind Period: Any other factor that, in the opinion of the investigator, would prevent the patient from complying with the requirements of the protocol.
- •Double-Blind Period: History of life-threatening transfusion reaction(s), allergy, anaphylactic reaction, or systemic response to human plasma-derived products.
- •Open-Label Period: Any adverse event(s) in the DB period and/or medical condition that, in the opinion of the investigator, might prevent the patient from safely participating in the OLE period of the study, including but not limited to: a. Occurrence of a life-threatening allergy, anaphylactic reaction, or systemic response to human plasma derived products. b. Received lung transplant, entered a waiting list for lung transplantation, or underwent lung surgery. The investigator should consult the sponsor before inclusion of any patient with a significant condition if the investigator believes that it will not pose an unacceptable risk for the patient.
- •Open-Label Period: Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally prescribed drugs, within the DB study or since the DB study.
- •Open-Label Period: Any smoking within the DB study or since the DB study.
- •Open-Label Period: Pregnancy or lactation.
- •Open-Label Period: Participation in another clinical trial since termination of participation in the DB period.
- •Open-Label Period: Inability to attend scheduled clinic visits and/or comply with study protocol.
- •Open-Label Period: 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.
- •Double-Blind Period: Two or more moderate or any severe exacerbation(s) within the year prior to the baseline visit.
- •Double-Blind Period: A moderate exacerbation within 6 weeks prior to the baseline.
- •Double-Blind Period: Use of oral or parenteral glucocorticoids in doses above 10 mg of prednisone daily or equivalent generics (substance and dose).
- •Double-Blind Period: 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.
- •Double-Blind Period: Hospitalization for any cause 6 weeks prior to screening.
- •Double-Blind Period: History of lung or liver transplant.
- •Double-Blind Period: On any thoracic or hepatic surgery waiting list.
结局指标
主要结局
FEV1 (L) post bronchodilator change from baseline at 104 weeks.
FEV1 (L) post bronchodilator change from baseline at 104 weeks.
次要结局
- Change from baseline over 104 weeks of treatment in CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC).
- Change from baseline over 104 weeks of treatment in Post bronchodilator spirometry measures a. FEV1 % of predicted b. FEV1/FVC %
- Exacerbations over 104 weeks of treatment; annual rate by severity and duration.
- Change from Baseline over 104 weeks of treatment in 6 minute walk test (6MWT).
研究者
Orit Pinchuk
Scientific
Kamada Ltd.
研究点 (6)
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