A Study to Evaluate the Safety and Efficacy of BEAM-302 in Adult Patients With Alpha-1 Antitrypsin Deficiency (AATD)

Официальное название

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

Обзор

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).

Вмешательства

• Препарат BEAM-302
  BEAM-302 is a lipid nanoparticle (LNP)-based therapy for the treatment of patients with AATD

Первичные конечные точки

• Phase 1 Dose Exploration: Rates of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [Срок оценки: 2 years]
• Phase 2 Dose Expansion: Absolute blood levels of total AAT [Срок оценки: 2 Years]

Вторичные конечные точки (2)

• Phase 1 Dose Exploration: Absolute blood levels of total AAT [Срок оценки: 2 Years]
• Phase 2 Dose Expansion: Rates of TEAEs and SAEs [Срок оценки: 2 Years]

Критерии участия

Part A:

Критерии включения

• 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.)

Критерии исключения

• 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.

Part B:

Критерии включения

• 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.)

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Clinical Study Center — Birmingham
• Clinical Study Center — Boston
• Clinical Study Center — Charleston

Австралия · 2 центра

• Clinical Study Center — Adelaide
• Clinical Study Center — Fitzroy

Новая Зеландия · 2 центра

• Clinical Study Center — Auckland
• Clinical Study Center — Hamilton

Великобритания · 2 центра

• Clinical Study Center — London
• Clinical Study Center — Southampton

Ирландия · 1 центр

• Clinical Study Center — Dublin

Нидерланды · 1 центр

• Clinical Study Center — Leiden

Идентификаторы

NCT: NCT06389877 · BTX-302-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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