Clinical trial NCT06389877: A Study to Evaluate the Safety and Efficacy of BEAM-302 in Adult Patients With Alpha-1 Antitrypsin Deficiency (AATD)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Alpha 1-Antitrypsin Deficiency
Lead sponsor: Beam Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2024-04-29
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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).

Primary outcomes:
measure: Phase 1 Dose Exploration: Rates of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: 2 years
measure: Phase 2 Dose Expansion: Absolute blood levels of total AAT
timeFrame: 2 Years
Secondary outcomes:
measure: Phase 1 Dose Exploration: Absolute blood levels of total AAT
timeFrame: 2 Years
measure: Phase 2 Dose Expansion: Rates of TEAEs and SAEs
timeFrame: 2 Years
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Clinical Study Center
city: Fitzroy
country: Australia
facility: Clinical Study Center
city: Leiden
country: Netherlands
facility: Clinical Study Center
city: Auckland
country: New Zealand
facility: Clinical Study Center
city: Hamilton
country: New Zealand
facility: Clinical Study Center
city: London
country: United Kingdom
facility: Clinical Study Center
Study officials:
affiliation: Beam Therapeutics
name: Medical Information
role: STUDY_DIRECTOR
References: