A Study of the Safety, Tolerability, PK, PD, and Efficacy of CRMA-1001 in Chronic Hepatitis B

Prior treatment

• Significant fibrosis or cirrhosis as defined by any of the following: a.      FibroScan result (CCI) during screening. A FibroScan obtained within the prior 12 months is acceptable if a report is available for investigator review. b.     Prior liver biopsy with (CCI)
• Receiving or expected to need any other systemic antiviral therapy at any time during participation in the study, with the exception of current NUC treatment and oral/topical therapy for HSV.

Other illness

• History of liver failure as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal varices.
• History or presence of a medical condition associated with liver disease other than HBV infection (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure, thalassemia, non-alcoholic steatohepatitis) or other known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Co-infection with HCV, HIV, or HDV as determined by Central Lab

Lab values

• AFP >100 ng/mL. a. Note: Participants with AFP >ULN but ≤100 ng/mL may be eligible if HCC can be ruled out based on a sensitive imaging study (e.g., contrast enhanced ultrasound, CT, or MRI during screening).
• ECG during screening showing clinically relevant abnormalities (including arrhythmias or marked QT abnormalities [QTcF < 300 msec or > 450 msec]), or other cardiac abnormalities that are considered clinically significant by the investigator. Known risk factors for Torsade de Pointes (e.g., hypokalemia, heart failure), or a personal or family history of congenital long QT syndrome.

Other

• Participant is pregnant or breastfeeding, or is planning a pregnancy or to breastfeed within 2 years of CRMA-1001 planned administration.

• Adults ≥ 18 to < 65 years of age, at the time of signing the informed consent.
• Chronic HBV infection, defined as positive for HBsAg for a duration of at least 6 months.
• On stable NUC treatment, defined as receiving the same NUC in the 6 months prior to enrollment, and expected to remain on the same NUC for the duration of study participation or until protocol-specified NUC discontinuation criteria are met. Tenofovir (as TAF, TDF, or tenofovir disoproxil maleate) and ETV are permitted.
• HBV DNA < 10 IU/mL (<1.0 log10 IU/mL) at Screening as determined by Central Lab.
• HBsAg ≥ 100 IU/mL (≥2.0 log10 IU/mL) at Screening as determined by Central Lab.
• Participant has the following laboratory parameters at screening by central laboratory: a. ALT and AST ≤ 1.5 × ULN, confirmed by local or central lab within 7 days of dosing if assessed prior to Day -28. b. Total bilirubin ≤ ULN (Note: isolated bilirubin ≤ 1.5 × ULN is acceptable for patients with documented Gilbert’s syndrome). c. PT, INR, and aPTT ≤ ULN (Note: PT and/or aPTT > ULN is acceptable if considered not clinically significant by investigator, INR and other parameters of liver function are within normal limits, and there are no current or historical concerns. Retesting is permitted). d. Hemoglobin ≥10 g/dL. e. Platelets ≥ the LLN. f. WBC ≤ ULN and ANC ≥1000/µl. g. eGFR ≥ 60 mL/min/1.73m2 (Inker, 2021). h. Albumin ≥ LLN
• Body weight of at least 45.0 kg and maximally 150.0 kg, and BMI within the range 18.0 to 32.0 kg/m2 (inclusive) at Screening.
• Male or female participants who agree to contraceptive requirements detailed in the protocol