a study to evaluate the safety and efficacy of beam-302 in adult patients with alpha-1 antitrypsin deficiency (aatd)

Conditions: Alpha 1-Antitrypsin Deficiency

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).