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

Alpha 1-Antitrypsin Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06389877
• Other study ID #: BTX-302-001
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: May 2024
• Est. completion date: August 2027

Study information

• Verified date: April 2024
• Source: Beam Therapeutics Inc.
• Contact: Medical Information
• Phone: 857-327-8641
• Email: clinicalinfo[@]beamtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 106
• Est. completion date: August 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency

Intervention

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

Locations

Country	Name	City	State
United Kingdom	Clinical Study Center	London

Sponsors (1)

Lead Sponsor	Collaborator
Beam Therapeutics Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase 2 Dose Expansion: Absolute blood levels of total AAT	Absolute Levels of AAT over time	2 Years
Secondary	Phase 1 Dose Exploration: Absolute blood levels of total AAT	Absolute Levels of AAT over time	2 Years
Secondary	Phase 2 Dose Expansion: Rates of TEAEs and SAEs	Numbers and percentages of patients reporting a given AE	2 Years