Chronic Hepatitis Delta
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of bulevirtide in combination with pegylated interferon in participants with chronic hepatitis delta (CHD).
Interventions
DRUGBulevirtide
Administered via subcutaneous injections
DRUGPeginterferon Alfa-2a (PEG-IFN alfa)
Administered via subcutaneous injections
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed consent form. * Positive serum 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. * Positive PCR results for serum/ plasma HDV RNA at screening. * Alanine transaminase level \>1 x upper limit of normal (ULN), but less than 10 x ULN. * Serum albumin \>28 g/L. * Thyroid stimulating hormone (TSH) within normal ranges (including on medication for control of thyroid function) * Negative urine pregnancy test for females of childbearing potential. * Inclusion criteria for female individuals: * 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 treatment period, or * Willingness to use highly effective contraception (double barrier method or barrier contraception in combination with hormonal or intrauterine contraceptive) throughout the treatment period and for 6 months after the last dose of the study medication. * Male 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 treatment period and for 6 months after the last dose of the study medication.
Exclusion criteria
* Child-Pugh hepatic insufficiency score of B-C or over 6 points. Note: Child-Pugh hepatic insufficiency score of 6 points is allowed. Only individuals with compensated cirrhosis are allowed. Uncomplicated oesophageal varices allowed; individuals with current bleeding or ligation, or history of bleeding or ligation within the last 2 years are excluded. * Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) coinfection. Individuals with HCV antibodies can be enrolled, if screening HCV RNA test is negative. * Creatinine clearance \< 60 mL/min as estimated using Cockcroft-Gault formula. * Total bilirubin ≥ 34.2 µmol/L. (Individuals 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.) * Evidence of an active or suspected malignancy, or an untreated pre-malignancy disorder, or a history of malignancy 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. * Systemic connective tissue disorders. * New York Heart Association (NYHA) class III-IV congestive heart failure. * Individuals with uncontrolled arterial hypertension: systolic blood pressure \> 150 mm Hg and/ or diastolic blood pressure \> 100 mm Hg at Screening. * Previous or unstable concurrent diseases or conditions that prevent individual's enrolment into the study. * Individuals with mental disorders or social circumstances that preclude them from following protocol requirements. * Current or previous decompensated liver disease, including coagulopathy, hepatic encephalopathy and esophageal varices hemorrhage. * 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 individauls from participation in this trial. Autoimmune hepatitis stigmata attributed to HDV infection in the opinion of the investigator are allowed. * White blood cells (WBC) count \< 3000 cells/mm\^3 (\<1500 if African individuals). * Absolute neutrophil count \< 1500 cells/mm\^3 (\<1000 if African individuals). * Platelet count \< 90,000 cells/mm\^3. * Haemoglobin \< 12 g/dL. * Use of prohibited psychotropic agents at Screening. * Use of interferons within 6 months before Screening. * History of solid organ transplantation. * Current alcohol abuse or alcohol abuse within 6 months prior to enrolment in this study; current drug addict or history of drug use within 2 years prior to Screening. * History of disease requiring regular use of systemic glucocorticosteroids (inhalative glucocorticosteroids are allowed) or other immunosuppressants. * Pregnant or breast-feeding females. * Participation in another clinical study with investigational drugs within 30 days prior to randomization. * Receipt of bulevirtide previously, e.g. in clinical trials. * Inability to follow protocol requirements and undergo all protocol procedures. Note: Individuals with medical contraindication for liver biopsy are allowed to participate in this study. Such individuals 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. * Contraindications, intolerance or hypersensitivity to interferons alfa, genetically engineered E.coli medications, polyethylene glycol or other components of peginterferon alfa-2а. * Presence or history of severe retinopathy, significant diabetic or hypertensive retinopathy. * Uncontrolled diabetes mellitus. * Uncontrolled cardiovascular disorders within 6 months before screening. * History of autoimmune disorder (e.g. myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, severe psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus) * Presence or history of significant psychiatric disorder (e.g. severe depression, suicide attempt, severe neurosis or cognitive disorder). * Presence or history of chronic lung disease with respiratory malfunction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virological Response at Week 24 After the Scheduled End of Treatment (SVR24) | 24 weeks after EOT (Week 72 for Arm A and study Week 120 for Arms B, C, and D) | SVR24 was defined as undetectable hepatitis delta virus (HDV) RNA (HDV RNA value \< lower limit of quantitation \[LLOQ\] with target not detected) at 24 weeks after the scheduled end of treatment (EOT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Undetectable HDV RNA at Week 96 (Arms B, C, and D Only) | Week 96 | Undetectable HDV RNA at Week 96 means undetectable (\< LLOQ, target not detected) HDV RNA at Week 96. |
| Percentage of Participants With Combined Response at Week 24 After the Scheduled End of Treatment | 24 weeks after EOT (Week 72 for Arm A and Week 120 for Arms B, C, and D) | Combined response was defined as fulfilment of 2 conditions simultaneously: 1) undetectable HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline, alanine aminotransferase (ALT) normalization, defined as an ALT value within the normal range, based on the central laboratories \[Russian sites: ≤ 31 U/L for females and ≤ 41 U/L for males; all other sites: ≤ 34 U/L for females and ≤ 49 U/L for males\]). |
| Percentage of Participants With Combined Response at Week 48 After the Scheduled End of Treatment | 48 weeks after EOT (Week 96 for Arm A and Week 144 for Arm B, C, and D) | Combined response is defined as fulfilment of 2 conditions simultaneously: 1) undetectable HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline, ALT normalization, defined as an ALT value within the normal range, based on the central laboratories \[Russian sites: ≤ 31 U/L for females and ≤ 41 U/L for males; all other sites: ≤ 34 U/L for females and ≤ 49 U/L for males\]). |
| Percentage of Participants With Undetectable HDV RNA at Week 48 | Week 48 | Undetectable HDV RNA at Week 48 means undetectable (\< LLOQ, target not detected) HDV RNA at Week 48. |
| Change From Baseline in Liver Stiffness as Measured by Elastography at Week 48 | Baseline, Week 48 | The mixed-effects models for repeated measurements (MMRM) model was used for analysis. |
| Change From Baseline in Liver Stiffness as Measured by Elastography at Week 96 | Baseline, Week 96 | The MMRM model was used for analysis. |
| Change From Baseline in Liver Stiffness as Measured by Elastography at Week 144 | Baseline, 48 weeks after EOT (Week 96 for Arm A and study Week 144 for Arms B, C, and D) | The MMRM model was used for analysis. |
| Percentage of Participants With Sustained Virological Response 48 After the Scheduled End of Treatment (SVR 48) | 48 weeks after EOT (Week 96 for Arm A; Week 144 for Arms B, C, and D) | SVR 48 is defined as undetectable hepatitis delta virus (HDV) RNA (HDV RNA value \< lower limit of quantitation \[LLOQ\] with target not detected) at 48 weeks after the scheduled end of treatment. |
Countries
France, Moldova, Romania, Russia
Participant flow
Recruitment details
Participants were enrolled at study sites in the France, Moldova, Romania and Russia.
Pre-assignment details
258 participants were screened. Participants were assigned to arms A: Pegylated Interferon Alfa-2a (PEG-IFN Alfa), B: Bulevirtide 2 mg/Day + PEG-IFN Alfa, C: Bulevirtide 10 mg/Day + PEG-IFN Alfa and D: Bulevirtide 10 mg/Day to the respective treatment.
Participants by arm
| Arm | Count |
|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) Participants received PEG-IFN alfa 180 microgram (mcg) once a week subcutaneously for 48 weeks with additional 48 weeks follow-up. | 25 |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa Participants received bulevirtide 2 mg once a day subcutaneously in combination with PEG-IFN alfa 180 mcg once a week subcutaneously for 48 weeks followed by bulevirtide 2 mg once a day for 48 weeks and additional 48 weeks follow-up. | 50 |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa Participants received bulevirtide 10 mg once a day subcutaneously in combination with PEG-IFN alfa 180 mcg once a week subcutaneously for 48 weeks followed by bulevirtide 10 mg once a day for 48 weeks and additional 48 weeks follow-up. | 50 |
| Bulevirtide 10 mg/Day Participants received bulevirtide 10 mg once a day subcutaneously for 96 weeks with additional 48 weeks follow-up. | 50 |
| Total~(N=174) | 175 |
| Total | 350 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 1 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 1 |
| Overall Study | Non-compliance with study drug | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 1 |
| Overall Study | Randomized but never treated | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal of consent | 5 | 8 | 1 | 1 |
Baseline characteristics
| Characteristic | Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Bulevirtide 2 mg/Day + PEG-IFN Alfa | Bulevirtide 10 mg/Day + PEG-IFN Alfa | Bulevirtide 10 mg/Day | Total~(N=174) |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 50 Participants | 49 Participants | 50 Participants | 174 Participants |
| Age, Continuous | 41 years STANDARD_DEVIATION 8.2 | 41 years STANDARD_DEVIATION 9.3 | 41 years STANDARD_DEVIATION 8.6 | 40 years STANDARD_DEVIATION 8.5 | 41 years STANDARD_DEVIATION 8.7 |
| HDV RNA | 5.20 log10 IU/mL STANDARD_DEVIATION 1.064 | 5.27 log10 IU/mL STANDARD_DEVIATION 1.355 | 5.09 log10 IU/mL STANDARD_DEVIATION 1.343 | 5.45 log10 IU/mL STANDARD_DEVIATION 1.098 | 5.26 log10 IU/mL STANDARD_DEVIATION 1.242 |
| Liver Stiffness | 15.8 kPa STANDARD_DEVIATION 11.57 | 12.8 kPa STANDARD_DEVIATION 6.43 | 12.5 kPa STANDARD_DEVIATION 7.6 | 12.7 kPa STANDARD_DEVIATION 6.65 | 13.1 kPa STANDARD_DEVIATION 7.72 |
| Race/Ethnicity, Customized Ethnicity, Not Collected | — | — | — | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 44 Participants | 43 Participants | 44 Participants | 152 Participants |
| Region of Enrollment France | 2 Participants | 3 Participants | 4 Participants | 2 Participants | 11 Participants |
| Region of Enrollment Moldova | 3 Participants | 7 Participants | 12 Participants | 9 Participants | 31 Participants |
| Region of Enrollment Romania | 6 Participants | 11 Participants | 12 Participants | 12 Participants | 41 Participants |
| Region of Enrollment Russia | 14 Participants | 29 Participants | 22 Participants | 27 Participants | 92 Participants |
| Sex: Female, Male Female | 6 Participants | 17 Participants | 15 Participants | 12 Participants | 50 Participants |
| Sex: Female, Male Male | 19 Participants | 33 Participants | 35 Participants | 38 Participants | 125 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 1 / 50 | 1 / 50 | 0 / 50 |
| other Total, other adverse events | 22 / 24 | 49 / 50 | 50 / 50 | 37 / 50 |
| serious Total, serious adverse events | 3 / 24 | 3 / 50 | 8 / 50 | 2 / 50 |
Outcome results
Primary
Percentage of Participants With Sustained Virological Response at Week 24 After the Scheduled End of Treatment (SVR24)
SVR24 was defined as undetectable hepatitis delta virus (HDV) RNA (HDV RNA value \< lower limit of quantitation \[LLOQ\] with target not detected) at 24 weeks after the scheduled end of treatment (EOT).
Time frame: 24 weeks after EOT (Week 72 for Arm A and study Week 120 for Arms B, C, and D)
Population: Full Analysis Set, is defined as all randomized participants who received at least 1 dose of study drug (Peg-IFNα and/or BLV).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Percentage of Participants With Sustained Virological Response at Week 24 After the Scheduled End of Treatment (SVR24) | 16.7 percentage of participants |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa | Percentage of Participants With Sustained Virological Response at Week 24 After the Scheduled End of Treatment (SVR24) | 32.0 percentage of participants |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa | Percentage of Participants With Sustained Virological Response at Week 24 After the Scheduled End of Treatment (SVR24) | 46.0 percentage of participants |
| Bulevirtide 10 mg/Day | Percentage of Participants With Sustained Virological Response at Week 24 After the Scheduled End of Treatment (SVR24) | 12.0 percentage of participants |
p-value: 0.000395% CI: [14.6, 50.4]Fisher Exact
p-value: 0.263195% CI: [-8.2, 34.2]Fisher Exact
p-value: 0.019795% CI: [1.8, 48.2]Fisher Exact
p-value: 0.718695% CI: [-26.3, 11.8]Fisher Exact
p-value: 0.218495% CI: [-5.5, 32.7]Fisher Exact
p-value: 0.028395% CI: [-36.1, -3.5]Fisher Exact
Secondary
Change From Baseline in Liver Stiffness as Measured by Elastography at Week 144
The MMRM model was used for analysis.
Time frame: Baseline, 48 weeks after EOT (Week 96 for Arm A and study Week 144 for Arms B, C, and D)
Population: Participants from Full Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 144 | -0.31 kPa |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 144 | -2.35 kPa |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 144 | -2.47 kPa |
| Bulevirtide 10 mg/Day | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 144 | -0.79 kPa |
p-value: 0.110395% CI: [-3.75, 0.39]MMRM
p-value: 0.153395% CI: [-4.88, 0.77]MMRM
p-value: 0.112995% CI: [-4.98, 0.53]MMRM
p-value: 0.675395% CI: [-3.34, 2.17]MMRM
p-value: 0.912495% CI: [-2.28, 2.04]MMRM
p-value: 0.152695% CI: [-0.59, 3.7]MMRM
Secondary
Change From Baseline in Liver Stiffness as Measured by Elastography at Week 48
The mixed-effects models for repeated measurements (MMRM) model was used for analysis.
Time frame: Baseline, Week 48
Population: Participants from Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 48 | -0.02 kPa |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 48 | -1.85 kPa |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 48 | -1.79 kPa |
| Bulevirtide 10 mg/Day | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 48 | -3.34 kPa |
p-value: 0.071795% CI: [-0.14, 3.26]MMRM
p-value: 0.156395% CI: [-4.39, 0.71]MMRM
p-value: 0.162695% CI: [-4.33, 0.73]MMRM
p-value: 0.009995% CI: [-5.87, -0.82]MMRM
p-value: 0.938495% CI: [-1.67, 1.81]MMRM
p-value: 0.087595% CI: [-3.2, 0.22]MMRM
Secondary
Change From Baseline in Liver Stiffness as Measured by Elastography at Week 96
The MMRM model was used for analysis.
Time frame: Baseline, Week 96
Population: Participants from Full Analysis Set with available data were analyzed. Per prespecified analysis, the data for this outcome measure was collected only for Arms B, C, and D at the scheduled Week 96 visit. Hence the data for Arm A is not reported for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 96 | -3.37 kPa |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 96 | -3.70 kPa |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa | Change From Baseline in Liver Stiffness as Measured by Elastography at Week 96 | -3.85 kPa |
p-value: 0.864595% CI: [-1.54, 1.83]MMRM
p-value: 0.703395% CI: [-2.06, 1.39]MMRM
p-value: 0.580695% CI: [-2.18, 1.23]MMRM
Secondary
Percentage of Participants With Combined Response at Week 24 After the Scheduled End of Treatment
Combined response was defined as fulfilment of 2 conditions simultaneously: 1) undetectable HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline, alanine aminotransferase (ALT) normalization, defined as an ALT value within the normal range, based on the central laboratories \[Russian sites: ≤ 31 U/L for females and ≤ 41 U/L for males; all other sites: ≤ 34 U/L for females and ≤ 49 U/L for males\]).
Time frame: 24 weeks after EOT (Week 72 for Arm A and Week 120 for Arms B, C, and D)
Population: Participants from Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Percentage of Participants With Combined Response at Week 24 After the Scheduled End of Treatment | 20.8 percentage of participants |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa | Percentage of Participants With Combined Response at Week 24 After the Scheduled End of Treatment | 36.0 percentage of participants |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa | Percentage of Participants With Combined Response at Week 24 After the Scheduled End of Treatment | 52.0 percentage of participants |
| Bulevirtide 10 mg/Day | Percentage of Participants With Combined Response at Week 24 After the Scheduled End of Treatment | 26.0 percentage of participants |
p-value: 0.013495% CI: [6, 44]Fisher Exact
Secondary
Percentage of Participants With Combined Response at Week 48 After the Scheduled End of Treatment
Combined response is defined as fulfilment of 2 conditions simultaneously: 1) undetectable HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline, ALT normalization, defined as an ALT value within the normal range, based on the central laboratories \[Russian sites: ≤ 31 U/L for females and ≤ 41 U/L for males; all other sites: ≤ 34 U/L for females and ≤ 49 U/L for males\]).
Time frame: 48 weeks after EOT (Week 96 for Arm A and Week 144 for Arm B, C, and D)
Population: Participants from Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Percentage of Participants With Combined Response at Week 48 After the Scheduled End of Treatment | 33.3 percentage of participants |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa | Percentage of Participants With Combined Response at Week 48 After the Scheduled End of Treatment | 32.0 percentage of participants |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa | Percentage of Participants With Combined Response at Week 48 After the Scheduled End of Treatment | 46.0 percentage of participants |
| Bulevirtide 10 mg/Day | Percentage of Participants With Combined Response at Week 48 After the Scheduled End of Treatment | 18.0 percentage of participants |
p-value: 0.004995% CI: [8.2, 45.1]Fisher Exact
Secondary
Percentage of Participants With Sustained Virological Response 48 After the Scheduled End of Treatment (SVR 48)
SVR 48 is defined as undetectable hepatitis delta virus (HDV) RNA (HDV RNA value \< lower limit of quantitation \[LLOQ\] with target not detected) at 48 weeks after the scheduled end of treatment.
Time frame: 48 weeks after EOT (Week 96 for Arm A; Week 144 for Arms B, C, and D)
Population: Participants from Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Percentage of Participants With Sustained Virological Response 48 After the Scheduled End of Treatment (SVR 48) | 25.0 percentage of participants |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa | Percentage of Participants With Sustained Virological Response 48 After the Scheduled End of Treatment (SVR 48) | 26.0 percentage of participants |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa | Percentage of Participants With Sustained Virological Response 48 After the Scheduled End of Treatment (SVR 48) | 46.0 percentage of participants |
| Bulevirtide 10 mg/Day | Percentage of Participants With Sustained Virological Response 48 After the Scheduled End of Treatment (SVR 48) | 12.0 percentage of participants |
p-value: 0.000395% CI: [14.6, 50.4]Fisher Exact
p-value: 195% CI: [-22.8, 21.4]Fisher Exact
p-value: 0.126595% CI: [-5.3, 42.2]Fisher Exact
p-value: 0.186395% CI: [-35.3, 5.4]Fisher Exact
p-value: 0.060195% CI: [1, 38.2]Fisher Exact
p-value: 0.124795% CI: [-29.9, 1.7]Fisher Exact
Secondary
Percentage of Participants With Undetectable HDV RNA at Week 48
Undetectable HDV RNA at Week 48 means undetectable (\< LLOQ, target not detected) HDV RNA at Week 48.
Time frame: Week 48
Population: Participants from Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Percentage of Participants With Undetectable HDV RNA at Week 48 | 20.8 percentage of participants |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa | Percentage of Participants With Undetectable HDV RNA at Week 48 | 40.0 percentage of participants |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa | Percentage of Participants With Undetectable HDV RNA at Week 48 | 60.0 percentage of participants |
| Bulevirtide 10 mg/Day | Percentage of Participants With Undetectable HDV RNA at Week 48 | 10.0 percentage of participants |
Secondary
Percentage of Participants With Undetectable HDV RNA at Week 96 (Arms B, C, and D Only)
Undetectable HDV RNA at Week 96 means undetectable (\< LLOQ, target not detected) HDV RNA at Week 96.
Time frame: Week 96
Population: Participants from Full Analysis Set were analyzed. Per prespecified analysis, the data for this outcome measure was collected only for Arms B, C, and D at the scheduled Week 96 visit. Hence the data for Arm A is not reported for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a (PEG-IFN Alfa) | Percentage of Participants With Undetectable HDV RNA at Week 96 (Arms B, C, and D Only) | 44.0 percentage of participants |
| Bulevirtide 2 mg/Day + PEG-IFN Alfa | Percentage of Participants With Undetectable HDV RNA at Week 96 (Arms B, C, and D Only) | 70.0 percentage of participants |
| Bulevirtide 10 mg/Day + PEG-IFN Alfa | Percentage of Participants With Undetectable HDV RNA at Week 96 (Arms B, C, and D Only) | 22.0 percentage of participants |