Chronic Hepatitis D Infection With Hepatitis B
Conditions
Keywords
Hepatitis D
Brief summary
This is a multicenter, open-label, randomized clinical trial to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination with Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients with Chronic Hepatitis D
Detailed description
This is a multicenter, open-label, randomised, phase II study. The study will be conducted in Russia and Germany. The study is designed to evaluate the benefit of 3 MXB doses versus observation in patients on background therapy with tenofovir, suffering from hepatitis delta with very limited therapeutic options; the patients will be randomized 1:1:1:1 into 3 treatment arms and an observation arm. Patients with compensated cirrhosis at screening will be stratified to allow similar distribution into each treatment arm. If patients were not receiving treatment with nucleoside/nucelotide analogue, the comparator/background drug will be initiated after the eligibility confirmation, for 12 weeks prior to randomization visit; patients who previously received tenofovir will continue the dosing; patients on different nucleoside/nucleotide analogue will be switched to tenofovir. Observation is considered an adequate control group, as daily placebo injections for 24 weeks are regarded not feasible and ethically questionable. It is planned to screen 200 patients, and 120 patients will be randomised into four treatment arms in the 1:1:1:1 ratio. * Arm A (30 patients): Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. * Arm B (30 patients): Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. * Arm C (30 patients): Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. * Arm D (30 patients): tenofovir treatment for 48 weeks.
Interventions
DRUGMyrcludex B
2 mg, once daily, subcutaneously
DRUGMyrcludex-B
5 mg, once daily, subcutaneously
DRUGTenofovir
tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Sponsors
Data Matrix Solutions
Hepatera Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicenter, Open-label, Randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age from 18 to 65 years inclusively at the time of signing Informed Consent Form. 2. Positive serum HBsAg for at least 6 months before Screening. 3. Positive serum anti-HDV antibody for at least 6 months before screening. 4. Positive PCR results for serum HDV RNA at Screening. 5. Patients with liver cirrhosis, irrespective of previous interferon treatment . 6. Patients without liver cirrhosis, who failed prior interferon treatment or for whom, in the opinion of the Investigator, such treatment is currently contraindicated (including history of interferon intolerance) . 7. Alanine aminotransferase level \>1 x ULN, but less than 10 x ULN. 8. Previous nucleotide/nucleoside analogue treatment within at least 12 weeks prior to the planned start of study treatment or subject's willingness to take tenofovir for at least 12 weeks prior to the planned start of study treatment. 9. Negative urine pregnancy test for females of childbearing potential. 10. Inclusion criteria for female subjects: * 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 throughout the study and for 3 months after the last dose of the study medication. 11. Male and female subjects must agree to use a highly effective contraception throughout the study and for 3 months after the last dose of the study medication. 12. Male subjects must agree not to donate sperm throughout the study and for 3 months after the last dose of the study medication.
Exclusion criteria
1. Child-Pugh score of B-C or over 6 points. 2. HCV or HIV coinfection. Subjects with anti-HCV antibodies can be enrolled, if screening HCV RNA test is negative. 3. Creatinine clearance \<60 mL/min. 4. Total bilirubin ≥ 2mg/dL. Patients with higher total bilirubin values may be included after the consultation with the Study's Medical Monitor, if such elevation can be clearly attributed to Gilbert's syndrome associated with low-grade hyperbilirubinemia. 5. Any previous or current malignant neoplasms, including hepatic carcinoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HDV RNA Response at Week 24 | 24 weeks | HDV RNA negativation or decrease by ≥2 log10 from baseline to Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | 24 weeks | Combined response: HDV RNA negativation or ≥2 log decline and normal ALT at treatment week 24 |
| Changes in ALT Values | 24 and 48 weeks | Changes in ALT values at Week 24 and Week 48 compared to baseline. |
| Change (Absence of Increase) in Fibrosis Marker | 24 and 48 weeks | Change (absence of increase) in fibrosis marker: serum alpha-2-macroglobulin at Week 24 and Week 48 compared to baseline |
| Durability of HDV RNA Response | 48 weeks | Durability of HDV RNA response to 24 weeks post treatment |
| Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline | 24 and 48 weeks | Change in hepatitis B virus (HBV) DNA levels at Week 24 and Week 48 compared to baseline. |
| Absence of a Fibrosis Progression According to the Findings of Transient Elastometry | 24 weeks | Decrease in liver stiffness and absence of a fibrosis progression according to the findings of transient elastometry (fibroscan) at week 24 compared to baseline |
| Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | 24 weeks | Change (improvement/ worsening) in fibrosis and histological activity stage according to the liver biopsy study results at week 24 compared to baseline. Liver fibrosis was evaluated by histological staging systems with stage 0 corresponding to absence of fibrosis and with the highest score (the last stage in all systems) corresponding to cirrhosis. Improvement is defined as a decrease of at least 1 point in histological staging systems; worsening is defined as an increase of at least 1 point. Data should be interpreted with caution due to low number of paired biopsies available. |
| Change in Hepatitis B Surface Antigen | 24 and 48 weeks | Changes in hepatitis B surface antigen (HBsAg) (defined as decline in HBsAg levels, disappearance of HBsAg and HBsAg seroconversion to anti-HBsAg) at week 24 and week 48 compared to baseline |
Countries
Germany, Russia
Participant flow
Recruitment details
Of 120 randomized patients 118 started treatment with study medication (2 patients from Tenofovir only group withdrew before treatment)
Participants by arm
| Arm | Count |
|---|---|
| Arm A Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.
Myrcludex B: 2 mg, once daily, subcutaneously
Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg | 28 |
| Arm B Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.
Myrcludex-B: 5 mg, once daily, subcutaneously
Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg | 32 |
| Arm C Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.
Myrcludex-B: 10 mg, once daily, subcutaneously
Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg | 30 |
| Arm D tenofovir treatment for 48 weeks
Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg | 28 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Progressive disease | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Arm C | Arm D | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 32 Participants | 30 Participants | 28 Participants | 118 Participants |
| Age, Continuous | 39.4 years STANDARD_DEVIATION 8.3 | 40.9 years STANDARD_DEVIATION 9.5 | 41.8 years STANDARD_DEVIATION 11.3 | 38.5 years STANDARD_DEVIATION 8.7 | 40.2 years STANDARD_DEVIATION 9.5 |
| Body Mass Index (kg/m²) <30 kg/m² | 27 participants | 31 participants | 28 participants | 22 participants | 108 participants |
| Body Mass Index (kg/m²) ≥30 kg/m² | 1 participants | 1 participants | 2 participants | 6 participants | 10 participants |
| Body Weight (kg) | 70.19 kg. STANDARD_DEVIATION 13.54 | 75.09 kg. STANDARD_DEVIATION 12.54 | 77.59 kg. STANDARD_DEVIATION 13.72 | 79.15 kg. STANDARD_DEVIATION 17.21 | 75.53 kg. STANDARD_DEVIATION 14.49 |
| Height (cm) | 168.5 cm. STANDARD_DEVIATION 8.3 | 172.9 cm. STANDARD_DEVIATION 7.4 | 173.8 cm. STANDARD_DEVIATION 9.8 | 172.8 cm. STANDARD_DEVIATION 9.4 | 172.0 cm. STANDARD_DEVIATION 8.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 1 Participants | 3 Participants | 5 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 30 Participants | 27 Participants | 23 Participants | 101 Participants |
| Sex: Female, Male Female | 13 Participants | 11 Participants | 7 Participants | 8 Participants | 39 Participants |
| Sex: Female, Male Male | 15 Participants | 21 Participants | 23 Participants | 20 Participants | 79 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 / 28 | 0 / 32 | 0 / 30 | 0 / 28 |
| other Total, other adverse events | 18 / 28 | 19 / 32 | 21 / 30 | 13 / 28 |
| serious Total, serious adverse events | 0 / 28 | 3 / 32 | 2 / 30 | 1 / 28 |
Outcome results
Primary
HDV RNA Response at Week 24
HDV RNA negativation or decrease by ≥2 log10 from baseline to Week 24
Time frame: 24 weeks
Population: mITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | HDV RNA Response at Week 24 | Responder | 15 Participants |
| Arm A | HDV RNA Response at Week 24 | Non-Responder | 13 Participants |
| Arm B | HDV RNA Response at Week 24 | Non-Responder | 16 Participants |
| Arm B | HDV RNA Response at Week 24 | Responder | 16 Participants |
| Arm C | HDV RNA Response at Week 24 | Responder | 23 Participants |
| Arm C | HDV RNA Response at Week 24 | Non-Responder | 7 Participants |
| Arm D | HDV RNA Response at Week 24 | Responder | 1 Participants |
| Arm D | HDV RNA Response at Week 24 | Non-Responder | 27 Participants |
Comparison: For each of the three Myrcludex B treatment groups, a null hypothesis of no clinically significant difference in proportion of responders compared to the control group (Tenofovir only), at week 24, were tested using the one-sided Wald test for superiority, at a one-sided overall significance level of 0.05 adjusted for multiple testing according to Bonferroni-Holm, with the superiority limit (test margin) set to 5%.p-value: <0.0001Bonferroni-Holm
Secondary
Absence of a Fibrosis Progression According to the Findings of Transient Elastometry
Decrease in liver stiffness and absence of a fibrosis progression according to the findings of transient elastometry (fibroscan) at week 24 compared to baseline
Time frame: 24 weeks
Population: mITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A | Absence of a Fibrosis Progression According to the Findings of Transient Elastometry | Change from Baseline to Week 24 | -2.85 kPa | Standard Deviation 2.65 |
| Arm A | Absence of a Fibrosis Progression According to the Findings of Transient Elastometry | Baseline | 14.45 kPa | Standard Deviation 6.37 |
| Arm B | Absence of a Fibrosis Progression According to the Findings of Transient Elastometry | Baseline | 17.18 kPa | Standard Deviation 11.49 |
| Arm B | Absence of a Fibrosis Progression According to the Findings of Transient Elastometry | Change from Baseline to Week 24 | -2.52 kPa | Standard Deviation 6.21 |
| Arm C | Absence of a Fibrosis Progression According to the Findings of Transient Elastometry | Baseline | 16.00 kPa | Standard Deviation 7.37 |
| Arm C | Absence of a Fibrosis Progression According to the Findings of Transient Elastometry | Change from Baseline to Week 24 | -3.38 kPa | Standard Deviation 3.83 |
| Arm D | Absence of a Fibrosis Progression According to the Findings of Transient Elastometry | Change from Baseline to Week 24 | -0.78 kPa | Standard Deviation 3.17 |
| Arm D | Absence of a Fibrosis Progression According to the Findings of Transient Elastometry | Baseline | 16.20 kPa | Standard Deviation 7.83 |
Secondary
Change (Absence of Increase) in Fibrosis Marker
Change (absence of increase) in fibrosis marker: serum alpha-2-macroglobulin at Week 24 and Week 48 compared to baseline
Time frame: 24 and 48 weeks
Population: mITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A | Change (Absence of Increase) in Fibrosis Marker | Change from Baseline to Week 24 | -0.076 g/L | Standard Deviation 0.32 |
| Arm A | Change (Absence of Increase) in Fibrosis Marker | Change from Baseline to Week 48 | -0.056 g/L | Standard Deviation 0.416 |
| Arm B | Change (Absence of Increase) in Fibrosis Marker | Change from Baseline to Week 48 | 0.075 g/L | Standard Deviation 0.36 |
| Arm B | Change (Absence of Increase) in Fibrosis Marker | Change from Baseline to Week 24 | 0.020 g/L | Standard Deviation 0.28 |
| Arm C | Change (Absence of Increase) in Fibrosis Marker | Change from Baseline to Week 24 | 0.024 g/L | Standard Deviation 0.257 |
| Arm C | Change (Absence of Increase) in Fibrosis Marker | Change from Baseline to Week 48 | -0.008 g/L | Standard Deviation 0.265 |
| Arm D | Change (Absence of Increase) in Fibrosis Marker | Change from Baseline to Week 24 | -0.141 g/L | Standard Deviation 0.607 |
| Arm D | Change (Absence of Increase) in Fibrosis Marker | Change from Baseline to Week 48 | -0.031 g/L | Standard Deviation 0.485 |
Comparison: Week 24. Two-sided van Elteren tests, stratified by presence of cirrhosis, were used to test for differences compared to the control group.~Separate comparisons were made for each of the three MXB groups versus the control group, and adjusted p-values were computed using the Bonferroni-Holm method.p-value: 0.7416Bonferroni-Holm
Comparison: Week 24p-value: 0.4434Bonferroni-Holm
Comparison: Week 24.p-value: 0.7371Bonferroni-Holm
Comparison: Week 48p-value: 1Bonferroni-Holm
Comparison: Week 48p-value: 0.9441Bonferroni-Holm
Comparison: Week 48p-value: 1Bonferroni-Holm
Secondary
Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline
Change in hepatitis B virus (HBV) DNA levels at Week 24 and Week 48 compared to baseline.
Time frame: 24 and 48 weeks
Population: mITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A | Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline | Change from Baseline to Week 24 | -0.314 IU/mL | Standard Deviation 0.956 |
| Arm A | Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline | Change from Baseline to Week 48 | -0.244 IU/mL | Standard Deviation 0.828 |
| Arm B | Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline | Change from Baseline to Week 48 | -0.194 IU/mL | Standard Deviation 1.416 |
| Arm B | Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline | Change from Baseline to Week 24 | -0.484 IU/mL | Standard Deviation 1.106 |
| Arm C | Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline | Change from Baseline to Week 24 | -0.173 IU/mL | Standard Deviation 1.144 |
| Arm C | Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline | Change from Baseline to Week 48 | -0.267 IU/mL | Standard Deviation 1.275 |
| Arm D | Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline | Change from Baseline to Week 24 | -0.343 IU/mL | Standard Deviation 1.151 |
| Arm D | Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline | Change from Baseline to Week 48 | -0.257 IU/mL | Standard Deviation 0.979 |
Comparison: Week 24. Two-sided van Elteren tests, stratified by presence of cirrhosis, were used to test for differences compared to the control group.~Tests were performed on log-10 transformed data. Separate comparisons were made for each of the three MXB groups versus the control group, and adjusted p-values were computed using the Bonferroni-Holm method.p-value: 1Bonferroni-Holm
Comparison: Week 24.p-value: 1Bonferroni-Holm
Comparison: Week 24p-value: 1Bonferroni-Holm
Comparison: Week 48p-value: 1Bonferroni-Holm
Comparison: Week 48p-value: 1Bonferroni-Holm
Comparison: Week 48p-value: 1Bonferroni-Holm
Secondary
Change in Hepatitis B Surface Antigen
Changes in hepatitis B surface antigen (HBsAg) (defined as decline in HBsAg levels, disappearance of HBsAg and HBsAg seroconversion to anti-HBsAg) at week 24 and week 48 compared to baseline
Time frame: 24 and 48 weeks
Population: mITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A | Change in Hepatitis B Surface Antigen | Change from Baseline to Week 24 | -0.048 IU/mL | Standard Deviation 0.392 |
| Arm A | Change in Hepatitis B Surface Antigen | Change from Baseline to Week 48 | -0.138 IU/mL | Standard Deviation 0.288 |
| Arm B | Change in Hepatitis B Surface Antigen | Change from Baseline to Week 48 | -0.162 IU/mL | Standard Deviation 0.412 |
| Arm B | Change in Hepatitis B Surface Antigen | Change from Baseline to Week 24 | 0.003 IU/mL | Standard Deviation 0.175 |
| Arm C | Change in Hepatitis B Surface Antigen | Change from Baseline to Week 24 | 0.034 IU/mL | Standard Deviation 0.106 |
| Arm C | Change in Hepatitis B Surface Antigen | Change from Baseline to Week 48 | -0.134 IU/mL | Standard Deviation 0.175 |
| Arm D | Change in Hepatitis B Surface Antigen | Change from Baseline to Week 24 | 0.025 IU/mL | Standard Deviation 0.239 |
| Arm D | Change in Hepatitis B Surface Antigen | Change from Baseline to Week 48 | -0.070 IU/mL | Standard Deviation 0.186 |
Comparison: Week 24. The change from baseline to Week 24 in HBsAg was performed using van Elteren tests. Tests were performed on log-10 transformed data.~Separare comparisons were made for each of the three Myrcludex B groups versus the control group, and the adjusted values were computed using the Bonferroni-Holm method.p-value: 0.5984Bonferroni-Holm
Comparison: Week 24p-value: 0.7529Bonferroni-Holm
Comparison: Week 24p-value: 0.3305Bonferroni-Holm
Comparison: Week 48p-value: 1Bonferroni-Holm
Comparison: Week 48p-value: 1Bonferroni-Holm
Comparison: Week 48p-value: 1Bonferroni-Holm
Secondary
Changes in ALT Values
Changes in ALT values at Week 24 and Week 48 compared to baseline.
Time frame: 24 and 48 weeks
Population: mITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A | Changes in ALT Values | Change from Baseline to Week 24 | -49.6 U/L | Standard Deviation 58.7 |
| Arm A | Changes in ALT Values | Change from Baseline to Week 48 | -1.6 U/L | Standard Deviation 72.8 |
| Arm B | Changes in ALT Values | Change from Baseline to Week 48 | -18.2 U/L | Standard Deviation 94.4 |
| Arm B | Changes in ALT Values | Change from Baseline to Week 24 | -79.4 U/L | Standard Deviation 84.2 |
| Arm C | Changes in ALT Values | Change from Baseline to Week 48 | 1.4 U/L | Standard Deviation 76 |
| Arm C | Changes in ALT Values | Change from Baseline to Week 24 | -78.9 U/L | Standard Deviation 81.1 |
| Arm D | Changes in ALT Values | Change from Baseline to Week 48 | -26.3 U/L | Standard Deviation 39 |
| Arm D | Changes in ALT Values | Change from Baseline to Week 24 | -29.2 U/L | Standard Deviation 61.4 |
Comparison: Week 24. The change from baseline to week 24 and week 48 in ALT levels was performed using van Elteren tests.~Fisher's exact test was used to test a null hypothesis of no difference in proportions (of patients with normal ALT values) against a two-sided alternative hypothesis. Separate tests were performed for each of the three Myrcludex B treatment groups against the control group, at week 24 and week 48, and adjusted p-values were computed using the Bonferroni-Holm method.p-value: 0.1642Bonferroni-Holm
Comparison: Week 24p-value: 0.0428Bonferroni-Holm
Comparison: Week 24p-value: 0.0428Bonferroni-Holm
Comparison: Week 48p-value: 0.2388Boferroni-Holm
Comparison: Week 48p-value: 0.7157Bonferroni-Holm
Comparison: Week 48p-value: 0.2388Bonferroni-Holm
Secondary
Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24
Combined response: HDV RNA negativation or ≥2 log decline and normal ALT at treatment week 24
Time frame: 24 weeks
Population: mITT
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arm A | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 24 | Responder | 6 Participants |
| Arm A | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 24 | Non-Responder | 22 Participants |
| Arm A | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 48 | Responder | 2 Participants |
| Arm A | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 48 | Non-Responder | 26 Participants |
| Arm B | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 24 | Non-Responder | 23 Participants |
| Arm B | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 48 | Responder | 1 Participants |
| Arm B | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 48 | Non-Responder | 31 Participants |
| Arm B | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 24 | Responder | 9 Participants |
| Arm C | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 48 | Responder | 1 Participants |
| Arm C | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 24 | Non-Responder | 19 Participants |
| Arm C | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 48 | Non-Responder | 29 Participants |
| Arm C | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 24 | Responder | 11 Participants |
| Arm D | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 48 | Non-Responder | 28 Participants |
| Arm D | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 24 | Non-Responder | 28 Participants |
| Arm D | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 24 | Responder | 0 Participants |
| Arm D | Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 | Week 48 | Responder | 0 Participants |
Comparison: Fisher's exact test was used to test a null hypothesis of no difference in proportions against a two-sided alternative hypothesis. Separate tests were performed for each of the three Myrcludex B treatment groups against the control group, at week 24 and week 48, and adjusted p-values were computered using the Bonferroni-Holm method.~This analysis, and presentation of descriptive statistics, was repeated for the subgroups of patients with normal/abnormal baseline ALT values.p-value: 0.0232Bonferroni-Holm
Comparison: Fisher's exact test was used to test a null hypothesis of no difference in proportions against a two-sided alternative hypothesis. Separate tests were performed for each of the three Myrcludex B treatment groups against the control group, at week 24 and week 48, and adjusted p-values were computered using the Bonferroni-Holm method.p-value: 0.0047Bonferroni-Holm
Comparison: Fisher's exact test was used to test a null hypothesis of no difference in proportions against a two-sided alternative hypothesis. Separate tests were performed for each of the three Myrcludex B treatment groups against the control group, at week 24 and week 48, and adjusted p-values were computered using the Bonferroni-Holm method.p-value: 0.001Bonferroni-Holm
Secondary
Durability of HDV RNA Response
Durability of HDV RNA response to 24 weeks post treatment
Time frame: 48 weeks
Population: mITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | Durability of HDV RNA Response | Response at Week 24 only | 15 Participants |
| Arm A | Durability of HDV RNA Response | Response at Week 24 and 48 | 2 Participants |
| Arm B | Durability of HDV RNA Response | Response at Week 24 and 48 | 1 Participants |
| Arm B | Durability of HDV RNA Response | Response at Week 24 only | 16 Participants |
| Arm C | Durability of HDV RNA Response | Response at Week 24 only | 23 Participants |
| Arm C | Durability of HDV RNA Response | Response at Week 24 and 48 | 3 Participants |
| Arm D | Durability of HDV RNA Response | Response at Week 24 only | 1 Participants |
| Arm D | Durability of HDV RNA Response | Response at Week 24 and 48 | 0 Participants |
Comparison: Week 48. Two-sided Fisher's exact tests were used to test null hypothesis of no difference in the proportion of responders compared to the Tenofovir only group. Separate comparisons were made for each of the three Myrcludex B groups versus the control group, and the adjusted p-values were computed using the Bonferroni-Holm method.p-value: 0.9818Bonferroni-Holm
Comparison: Week 48. Two-sided Fisher's exact tests were used to test null hypothesis of no difference in the proportion of responders compared to the Tenofovir only group. Separate comparisons were made for each of the three Myrcludex B groups versus the control group, and the adjusted p-values were computed using the Bonferroni-Holm method.p-value: 1Bonferroni-Holm
Comparison: Week 48. Two-sided Fisher's exact tests were used to test null hypothesis of no difference in the proportion of responders compared to the Tenofovir only group. Separate comparisons were made for each of the three Myrcludex B groups versus the control group, and the adjusted p-values were computed using the Bonferroni-Holm method.p-value: 0.7132Bonferroni-Holm
Secondary
Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results
Change (improvement/ worsening) in fibrosis and histological activity stage according to the liver biopsy study results at week 24 compared to baseline. Liver fibrosis was evaluated by histological staging systems with stage 0 corresponding to absence of fibrosis and with the highest score (the last stage in all systems) corresponding to cirrhosis. Improvement is defined as a decrease of at least 1 point in histological staging systems; worsening is defined as an increase of at least 1 point. Data should be interpreted with caution due to low number of paired biopsies available.
Time frame: 24 weeks
Population: mITT
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | Improvement | 1 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | Worsening | 1 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | Worsening | 4 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | Worsening | 3 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | Improvement | 2 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | No change | 4 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | Improvement | 1 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | No change | 3 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | No change | 0 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | No change | 2 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | Worsening | 4 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | Improvement | 4 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | Improvement | 2 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | Worsening | 3 Participants |
| Arm A | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | No change | 1 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | No change | 2 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | Worsening | 2 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | No change | 2 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | Worsening | 2 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | No change | 1 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | No change | 1 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | Improvement | 2 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | Improvement | 2 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | Worsening | 3 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | Improvement | 1 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | Worsening | 2 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | No change | 1 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | Worsening | 2 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | Improvement | 1 Participants |
| Arm B | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | Improvement | 1 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | No change | 4 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | Improvement | 3 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | No change | 2 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | Worsening | 2 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | Improvement | 3 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | No change | 2 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | Worsening | 2 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | Improvement | 3 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | Worsening | 0 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | Improvement | 3 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | No change | 3 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | Worsening | 1 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | Improvement | 3 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | No change | 1 Participants |
| Arm C | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | Worsening | 3 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | Improvement | 1 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | No change | 1 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | Worsening | 1 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | Worsening | 2 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | No change | 0 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | Improvement | 1 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | Improvement | 3 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Knodell fibrosis score | Improvement | 2 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Ishak fibrosis score | Worsening | 2 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | Worsening | 1 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | Improvement | 3 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | Worsening | 1 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Histological activity index | No change | 0 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir activity grade | No change | 0 Participants |
| Arm D | Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results | Metavir fibrosis stage | No change | 2 Participants |