Alpha 1-Antitrypsin Deficiency
Conditions
Brief summary
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).
Interventions
DRUGBEAM-302
BEAM-302 is a lipid nanoparticle (LNP)-based therapy for the treatment of patients with AATD
Sponsors
Beam Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Part A: 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.)
Exclusion criteria
* 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: 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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 Dose Exploration: Rates of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | 2 years | Numbers and percentages of patients reporting a given AE |
| Phase 2 Dose Expansion: Absolute blood levels of total AAT | 2 Years | Absolute Levels of AAT over time |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 Dose Exploration: Absolute blood levels of total AAT | 2 Years | Absolute Levels of AAT over time |
| Phase 2 Dose Expansion: Rates of TEAEs and SAEs | 2 Years | Numbers and percentages of patients reporting a given AE |
Countries
Australia, Ireland, Netherlands, New Zealand, United Kingdom, United States
Contacts
CONTACTMedical Information
STUDY_DIRECTORMedical Information
Beam Therapeutics
Outcome results
None listed