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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Alpha 1-Antitrypsin Deficiency
• Intervention / Treatment: Drug: BEAM-302

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 857-327-8641; Email: clinicalinfo@beamtx.com

Study Locations

• Australia
  • Adelaide, Australia
    • Recruiting
    • Clinical Study Center
  • Fitzroy, Australia
    • Recruiting
    • Clinical Study Center
• Ireland
  • Dublin, Ireland
    • Recruiting
    • Clinical Study Center
• Netherlands
  • Leiden, Netherlands
    • Recruiting
    • Clinical Study Center
• New Zealand
  • Auckland, New Zealand
    • Recruiting
    • Clinical Study Center
  • Hamilton, New Zealand
    • Recruiting
    • Clinical Study Center
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Clinical Study Center
  • Southampton, United Kingdom
    • Recruiting
    • Clinical Study Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Clinical Study Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Clinical Study Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Clinical Study Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.)

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BEAM-302 Drug Product	Drug: BEAM-302; BEAM-302 is a lipid nanoparticle (LNP)-based therapy for the treatment of patients with AATD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 Dose Exploration: Rates of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	Numbers and percentages of patients reporting a given AE	2 years
Phase 2 Dose Expansion: Absolute blood levels of total AAT	Absolute Levels of AAT over time	2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 Dose Exploration: Absolute blood levels of total AAT	Absolute Levels of AAT over time	2 Years
Phase 2 Dose Expansion: Rates of TEAEs and SAEs	Numbers and percentages of patients reporting a given AE	2 Years

Collaborators and Investigators

• Sponsor: Beam Therapeutics Inc.
• Investigators: Study Director: Medical Information, Beam Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: April 22, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Emphysema; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: BTX-302-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes