NCT06389877招募中1 期
A Phase 1/2 Dose-exploration and Dose-expansion Study to Evaluate the Safety and Efficacy of BEAM-302 in Adult Patients With Alpha-1 Antitrypsin Deficiency (AATD)-Associated Lung Disease and/or Liver Disease
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 106
- 试验地点
- 11
- 主要终点
- Phase 1 Dose Exploration: Rates of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
研究概览
简要总结
This is a Phase 1/2, multicenter, open-label, dose-exploration (Phase 1) and dose-expansion (Phase 2) study to evaluate the safety, tolerability, PK/PD, and efficacy of BEAM-302 in adult patients with AATD-associated lung disease and/or liver disease and to determine the optimal biological dose (OBD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria:
- •Males or females 18 - 70 years of age inclusive at the time of consent.
- •Diagnosis of AATD and homozygous for the PiZZ mutation (confirmed by genetic testing).
- •Blood total AAT level <11 μM or equivalent protein in mg/dL.
- •Patients receiving augmentation therapy in regions where augmentation is not SoC must be willing to washout augmentation therapy for at least 6 weeks prior to signing the ICF and for the length of the study (unless clinically indicated)
- •A postbronchodilator FEV1 ≥40% of predicted and an FEV1/FVC <70% at screening. (PFTs obtained within 1 year of signing the ICF may be used for eligibility.)
- •Evidence of emphysema on a historic CT scan or a DLCO ≤70% of the predicted value (corrected for hemoglobin) at screening. (PFTs obtained within 1 year of signing the ICF may be used for eligibility.)
排除标准
- •Body mass index >30
- •Lung or liver transplant or on waiting list for lung or liver transplant or status post lung volume reduction surgery.
- •Clinical evidence of severe bronchiectasis as per the discretion of the investigator (eg, excessive sputum production or recurrent infections requiring antibiotic use [>4x/year]).
- •Liver disease with any of the following:
- •FibroScan liver stiffness measurement ≥7.5 kilopascals (kPa). (For sites without access to FibroScan, APRI >0.5 can be used as a surrogate exclusion criterion [Yilmaz, 2011].
- •Known history of liver cirrhosis or complications of cirrhosis (eg, varices, ascites, hepatic encephalopathy).
- •Presence of ≥F2 liver fibrosis if a patient has previously had a liver biopsy.
- •Have ALT or AST > upper limit of normal (ULN).
- •Total bilirubin levels > ULN; if documented Gilbert's Syndrome, total bilirubin >2 × ULN.
- •INR ≥1.2 at screening. If deemed appropriate by the investigator and/or prescribing physician, the patient may stop taking anticoagulants for an appropriate washout period or reversal with vitamin K and if indicated, a repeat INR within <1.2 would be acceptable.
- •Seropositive for hepatitis B (positive surface Ag).
- •Active hepatitis C by hepatitis C virus (HCV) antibody. If HCV antibody positive, must be HCV RNA polymerase chain reaction (PCR) negative.
- •Inclusion Criteria:
- •Males or females 18 - 70 years of age inclusive at the time of consent.
- •Diagnosis of AATD and homozygous for the PiZZ mutation (confirmed by genetic testing).
- •Evidence of METAVIR F1, F2, or F3 liver fibrosis based on a central read of a baseline liver biopsy during the screening period or a histological diagnosis made no more than 6 months before enrollment and stage confirmed by central read.
- •A postbronchodilator FEV1 ≥40% of predicted at screening. (PFTs obtained within 1 year of signing the ICF may be used for eligibility.)
- •Exclusion Criteria:
- •Lung or liver transplant or on waiting list for lung or liver transplant or status post lung volume reduction surgery.
- •Clinical evidence of severe bronchiectasis as per the discretion of the investigator (eg, excessive sputum production or recurrent infections requiring antibiotic use [>4x/year])
- •Previous diagnosis of liver cirrhosis or complications of cirrhosis (eg, varices, ascites, hepatic encephalopathy).
研究组 & 干预措施
BEAM-302 Drug Product
Experimental
干预措施: BEAM-302 (Drug)
结局指标
主要结局
Phase 1 Dose Exploration: Rates of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
时间窗: 2 years
Numbers and percentages of patients reporting a given AE
Phase 2 Dose Expansion: Absolute blood levels of total AAT
时间窗: 2 Years
Absolute Levels of AAT over time
次要结局
- Phase 1 Dose Exploration: Absolute blood levels of total AAT(2 Years)
- Phase 2 Dose Expansion: Rates of TEAEs and SAEs(2 Years)
研究者
研究点 (11)
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