Study to Assess Efficacy and Safety of Bulevirtide in Participants With Chronic Hepatitis Delta (CHD)
Condition: Chronic Hepatitis Delta
MeSH terms: Hepatitis A; Hepatitis D; Hepatitis; Hepatitis, Chronic
Intervention: Bulevirtide
Intervention description: Administered via SC injections
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 150.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the efficacy of bulevirtide for treatment
      of chronic hepatitis delta (CHD) in comparison to delayed treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of signed and dated informed consent form.

          2. Positive serum anti-hepatitis delta virus (HDV) antibody results or polymerase chain
             reaction (PCR) results for serum/ plasma HDV ribonucleic acid (RNA) for at least 6
             months before screening.

          3. Positive PCR results for serum/plasma HDV RNA at screening.

          4. Alanine transaminase level > 1 x upper limit of normal (ULN), but less than 10 x ULN.

          5. Serum albumin > 28 g/L.

          6. Negative urine pregnancy test for females of childbearing potential.

          7. Inclusion criteria for females:

               -  Postmenopausal for at least 2 years, or

               -  Surgically sterile (total hysterectomy or bilateral oophorectomy, bilateral tubal
                  ligation, staples, or another type of sterilization), or

               -  Abstinence from heterosexual intercourse throughout the study, or

               -  Willingness to use highly effective contraception (double barrier method or
                  barrier contraception in combination with hormonal or intrauterine contraceptive)
                  throughout the study and for 3 months after the last dose of the study medication
                  for participants discontinued during the treatment period.

          8. Individuals must agree to use a highly effective contraception (double barrier method
             or barrier contraception in combination with hormonal or intrauterine contraceptive
             used by female partners) and not to donate sperm throughout the study and for 3 months
             after the last dose of the study medication for participants discontinued during the
             treatment period.

        Exclusion Criteria:

          1. Child-Pugh hepatic insufficiency score over 7 points. Uncomplicated oesophageal
             varices allowed; Individuals with current bleeding or ligation, or history of bleeding
             or ligation within the last 2 years are excluded.

          2. Hepatitis C virus (HCV) or uncontrolled human immunodeficiency virus (HIV)
             coinfection. Individuals with HCV antibodies can be enrolled, if screening HCV RNA
             test is negative. Individuals with HIV infection can be enrolled if cluster of
             differentiation (CD4+) cell counts are >500/mL and HIV RNA is below limit of detection
             for at least 12 months.

          3. Creatinine clearance < 60 mL/min as estimated using Cockcroft-Gault formula.

          4. Total bilirubin ≥ 34.2 µmol/L. (Participants with higher total bilirubin values may be
             included after the consultation with the Study Medical Monitor, if such elevation can
             be clearly attributed to Gilbert's syndrome associated with low-grade
             hyperbilirubinemia.)

          5. Evidence of an active or suspected malignancy or a history of malignancy, or an
             untreated pre-malignancy disorder within the last 5 years (with the exception of
             successfully treated carcinoma of the cervix in situ and successfully treated basal
             cell carcinoma and squamous cell carcinoma not less than 1 year prior to screening
             [and no more than 3 excised skin cancer within the last 5 years prior to screening])
             or history of hepatic carcinoma.

          6. Systemic connective tissue disorders.

          7. New York Heart Association (NYHA) class III-IV congestive heart failure.

          8. Participants with uncontrolled arterial hypertension: systolic blood pressure > 150 mm
             Hg and/ or diastolic blood pressure > 100 mm Hg at Screening.

          9. Previous or unstable concurrent diseases or conditions that prevent individual's
             enrolment into the study.

         10. Participants with mental disorders or social circumstances that preclude them from
             following protocol requirements.

         11. Current or previous (within last 2 years) decompensated liver disease, including
             coagulopathy, hepatic encephalopathy and esophageal varices hemorrhage.

         12. One or more additional known primary or secondary causes of liver disease, other than
             hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic
             involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other
             congenital or metabolic conditions affecting the liver, congestive heart failure or
             other severe cardiopulmonary disease, etc.). Gilbert's syndrome, a benign disorder
             associated with low-grade hyperbilirubinemia, will not exclude patients from
             participation in this trial. Autoimmune hepatitis stigmata attributed to HDV infection
             in the opinion of the investigator are allowed.

         13. White blood cells (WBC) count < 3000 cells/mm^3 (<1500 if African participants).

         14. Neutrophil count < 1500 cells/mm^3 (<1000 if African participants).

         15. Platelet count < 60,000 cells/mm^3.

         16. Use of prohibited psychotropic agents at Screening.

         17. Use of interferons within 6 months before Screening.

         18. History of solid organ transplantation.

         19. Current alcohol abuse or alcohol abuse within 6 months prior to enrolment in this
             study; past or current drug addict.

         20. History of disease requiring regular use of systemic glucocorticosteroids (inhalative
             glucocorticosteroids are allowed) or other immunosuppressants.

         21. Pregnant or breast-feeding females.

         22. Participation in another clinical study with investigational drugs within 30 days
             prior to randomization.

         23. Receipt of bulevirtide previously, e.g. in clinical trials.

         24. Inability to follow protocol requirements and undergo all protocol procedures. NOTE:
             Participants with medical contraindication for liver biopsy are allowed to participate
             in this study. Such participants will exempt from liver biopsy requirements in this
             study.

        Individuals receiving prohibited treatment at Screening cannot be included into the study
        unless this treatment is withdrawn prior to randomization.