Evaluating BEAM-302 for treating Alpha-1 Antitrypsin Deficiency in adults

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 study is testing a new treatment called BEAM-302 to see if it can help adults with Alpha-1 Antitrypsin Deficiency who have lung or liver problems.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 106 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Beam Therapeutics Inc. (industry)
• Locations: 11 sites (Birmingham, Alabama and 10 other locations)
• Trial ID: NCT06389877 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 clinical trial is designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of BEAM-302 in adult patients suffering from Alpha-1 Antitrypsin Deficiency (AATD) with associated lung and/or liver disease. The study will involve a multicenter approach, starting with a dose-exploration phase followed by a dose-expansion phase to determine the optimal biological dose. Participants will be closely monitored for their response to the treatment and any adverse effects throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 70 with a confirmed diagnosis of AATD and specific lung function criteria.

Not a fit: Patients with a body mass index over 30 or those who have undergone lung or liver transplants will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve lung and liver function in patients with AATD.

How similar studies have performed: While this approach is novel, similar studies targeting genetic therapies for AATD have shown promise in preliminary phases.

Eligibility 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.)

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).

Where this trial is running

Birmingham, Alabama and 10 other locations

• Clinical Study Center — Birmingham, Alabama, United States (RECRUITING)
• Clinical Study Center — Boston, Massachusetts, United States (RECRUITING)
• Clinical Study Center — Charleston, South Carolina, United States (RECRUITING)
• Clinical Study Center — Adelaide, Australia (RECRUITING)
• Clinical Study Center — Fitzroy, Australia (RECRUITING)
• Clinical Study Center — Dublin, Ireland (RECRUITING)
• Clinical Study Center — Leiden, Netherlands (RECRUITING)
• Clinical Study Center — Auckland, New Zealand (RECRUITING)
• Clinical Study Center — Hamilton, New Zealand (RECRUITING)
• Clinical Study Center — London, United Kingdom (RECRUITING)
• Clinical Study Center — Southampton, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Medical Information

Conditions: Alpha 1-Antitrypsin Deficiency