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CompletedNCT03852719Updated Aug 22, 2025Results posted

Study to Assess Efficacy and Safety of Bulevirtide in Participants With Chronic Hepatitis Delta (CHD)

A Phase 3 interventional study of Bulevirtide in Chronic Hepatitis Delta, sponsored by Gilead Sciences. Completed at 19 sites in 5 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-08-22.

Sponsored by Gilead Sciences · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
150
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The primary objective of this study is to evaluate the efficacy of bulevirtide administered subcutaneously (SC) for 48 weeks at a dose of 2 mg or 10 mg once daily for treatment of chronic hepatitis delta (CHD) in comparison to delayed treatment.

The main goal of this study is to determine the effectiveness of bulevirtide in participants randomized to bulevirtide 2 mg or 10 mg once daily SC as compared to participants randomized to delayed treatment for 48 weeks. Treatment will continue through Week 144 (participants randomized to delayed treatment will change to bulevirtide 10 mg once daily SC after Week 48 through Week 144). All participants will be followed off-treatment for an additional 96 weeks.

02

Conditions studied

  • Chronic Hepatitis Delta

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03

In context

Hepatitis D, Chronic

40 studies on the registry are indexed under Hepatitis D, Chronic; 8 are open to participants now.

This study's enrollment of 150 is above the median of 33 across 29 interventional studies indexed under Hepatitis D, Chronic.

Browse Hepatitis D, Chronic studies →

Lead sponsor

Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 249 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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 individuals 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 individuals 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. (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.)
  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. Individuals 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. Individuals 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 individuals 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 individuals).
  14. Neutrophil count \< 1500 cells/mm\^3 (\<1000 if African individuals).
  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: 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.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
150 participants (actual)

Study arms

  • Experimental
    Delayed Treatment/Bulevirtide 10 mg/day

    After an observational period of 48 weeks, participants will receive treatment with bulevirtide 10 mg/day subcutaneously (SC) for 96 weeks and will be followed for up to 96 weeks (Up to Week 240).

    Drug: Bulevirtide

  • Experimental
    Bulevirtide 2 mg/day

    Participants will receive bulevirtide 2 mg/day SC for 144 weeks and will be followed for up to 96 weeks (Up to Week 240).

    Drug: Bulevirtide

  • Experimental
    Bulevirtide 10 mg/day

    Participants will receive bulevirtide 10 mg/day SC for 144 weeks and will be followed for up to 96 weeks (Up to Week 240).

    Drug: Bulevirtide

Interventions

  • DrugBulevirtide

    Administered via SC injections

    Also known as: Myrcludex B, Hepcludex®

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With Combined Response at Week 48

    Combined response was defined as fulfilment of two conditions simultaneously: Undetectable (\< lower limit of quantification (LLOQ, target not detected)) HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline; and ALT normalization.

    Time frame: Week 48

Secondary outcomes

  1. 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

  2. Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48

    ALT normalization was 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: Week 48

  3. Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 48

    ANCOVA was used for analysis.

    Time frame: Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 48

  4. Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 96

    Mixed model for repeated measurements (MMRM) was used for analysis.

    Time frame: Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 96

  5. Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 144

    MMRM was used for analysis.

    Time frame: Baseline, Week 144

  6. Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 192

    MMRM was used for analysis.

    Time frame: Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 192

  7. Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 240

    MMRM was used for analysis.

    Time frame: Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 240

  8. Percentage of Participants With Undetectable HDV RNA 24 Weeks After Scheduled End of Treatment (Sustained Virological Response)

    Undetectable HDV RNA 24 Weeks after Scheduled End of Treatment means undetectable (\< LLOQ, target not detected) HDV RNA at Week 168

    Time frame: Week 168

  9. Percentage of Participants With Undetectable HDV RNA 48 Weeks After Scheduled End of Treatment (Sustained Virological Response)

    Undetectable HDV RNA 48 Weeks after Scheduled End of Treatment means undetectable (\< LLOQ, target not detected) HDV RNA at Week 192

    Time frame: Week 192

  10. Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event (AE) by Week 144

    An AE was defined as any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.

    Time frame: Delayed Treatment/Bulevirtide 10 mg/day arm: Week 48 up to Week 144; Bulevirtide 2mg/day and 10 mg/day arms: First dose date up to Week 144

07

Results

Posted Oct 28, 2022

Participant flow

Participants were enrolled at study sites in Germany, Italy, Russia, and Sweden.

Participant flow — Overall Study
MilestoneDelayed Treatment/Bulevirtide 10 mg/DayBulevirtide 2 mg/DayBulevirtide 10 mg/Day
Started514950
Did not receive bulevirtide100
Completed282830
Not completed232120
Withdrew: Withdrawal of consent889
Withdrew: Physician decision541
Withdrew: Pregnancy210
Withdrew: Death100
Withdrew: Reason not specified335
Withdrew: Adverse event214
Withdrew: Progressive disease141
Withdrew: Lost to follow-up100

Outcome measures

PrimaryPercentage of Participants With Combined Response at Week 48

Combined response was defined as fulfilment of two conditions simultaneously: Undetectable (\< lower limit of quantification (LLOQ, target not detected)) HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline; and ALT normalization.

Time frame:
Week 48
Reported as:
Number · percentage of participants
Percentage of Participants With Combined Response at Week 48
percentage of participantsDelayed TreatmentBulevirtide 2 mg/DayBulevirtide 10 mg/Day
Percentage of Participants With Combined Response at Week 482.0 (0.0 to 10.4)44.9 (30.7 to 59.8)48.0 (33.7 to 62.6)
Statistical analysis
  • Delayed Treatment vs Bulevirtide 10 mg/Day · Fisher Exact · p = <0.0001 (Fisher's exact test was used for comparison of bulevirtide 10 mg versus Delayed Treatment using a significance level of 0.04 at Week 48.) · Difference in percentages: 46.0 · 96% CI 30.5 to 61.4
  • Delayed Treatment vs Bulevirtide 2 mg/Day · Fisher Exact · p = <0.0001 (Fisher's exact test was used for comparison of bulevirtide 2 mg versus Delayed Treatment using a significance level of 0.04 at Week 48.) · Difference in percentages: 42.9 · 96% CI 27.0 to 58.5
SecondaryPercentage 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
Reported as:
Number · percentage of participants
Percentage of Participants With Undetectable HDV RNA at Week 48
percentage of participantsDelayed TreatmentBulevirtide 2 mg/DayBulevirtide 10 mg/Day
Percentage of Participants With Undetectable HDV RNA at Week 480 (0.0 to 7.0)12.2 (4.6 to 24.8)20.0 (10.0 to 33.7)
Statistical analysis
  • Bulevirtide 2 mg/Day vs Bulevirtide 10 mg/Day · Fisher Exact · p = 0.4139 (Fisher's exact test was used for the comparison of bulevirtide 10 mg versus bulevirtide 2 mg using a significance level of 0.04 at Week 48.) · Difference in percentages: 7.8 · 96% CI -8.5 to 24.3
SecondaryPercentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48

ALT normalization was 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:
Week 48
Reported as:
Number · percentage of participants
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48
percentage of participantsDelayed TreatmentBulevirtide 2 mg/DayBulevirtide 10 mg/Day
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 4811.8 (4.4 to 23.9)51.0 (36.3 to 65.6)56.0 (41.3 to 70.0)
Statistical analysis
  • Delayed Treatment vs Bulevirtide 2 mg/Day · Fisher Exact · p = <0.0001 (Fisher's exact test was used for comparison of bulevirtide 2 mg versus Delayed treatment using a significance level of 0.05.) · Difference in percentages: 39.3 · 95% CI 20.0 to 55.8
  • Delayed Treatment vs Bulevirtide 10 mg/Day · Fisher Exact · p = <0.0001 (Fisher's exact test was used for comparison of bulevirtide 10 mg versus Delayed treatment using a significance level of 0.05.) · Difference in percentage: 44.2 · 95% CI 25.8 to 59.9
SecondaryChange From Baseline in Liver Stiffness, as Measured by Elastography at Week 48

ANCOVA was used for analysis.

Time frame:
Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 48
Reported as:
Least squares mean · kPa
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 48
kPaDelayed TreatmentBulevirtide 2 mg/DayBulevirtide 10 mg/DayDelayed Treatment / /Bulevirtide 10 mg/Day
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 480.87 (-0.79 to 2.53)-3.06 (-4.67 to -1.45)-3.16 (-4.88 to -1.43)-3.36 (-4.60 to -2.12)
Statistical analysis
  • Delayed Treatment vs Bulevirtide 10 mg/Day · ANCOVA · p = 0.0010 · Difference in ls mean: -4.02 · 95% CI -6.39 to -1.65
  • Delayed Treatment vs Bulevirtide 2 mg/Day · ANCOVA · p = 0.0009 · Difference in ls mean: -3.93 · 95% CI -6.23 to -1.63
SecondaryChange From Baseline in Liver Stiffness, as Measured by Elastography at Week 96

Mixed model for repeated measurements (MMRM) was used for analysis.

Time frame:
Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 96
Reported as:
Least squares mean · kPa
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 96
kPaBulevirtide 2 mg/DayBulevirtide 10 mg/DayDelayed Treatment/Bulevirtide 10 mg/Day
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 96-4.31 (-5.54 to -3.08)-4.88 (-6.11 to -3.65)-4.20 (-5.41 to -2.98)
Statistical analysis
  • Bulevirtide 2 mg/Day vs Bulevirtide 10 mg/Day · MMRM · p = 0.5156 · Difference in least square (ls) mean: 0.57 · 95% CI -1.16 to 2.30
SecondaryChange From Baseline in Liver Stiffness, as Measured by Elastography at Week 144

MMRM was used for analysis.

Time frame:
Baseline, Week 144
Reported as:
Least squares mean · kPa
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 144
kPaBulevirtide 2 mg/DayBulevirtide 10 mg/Day
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 144-5.24 (-6.85 to -3.63)-4.03 (-5.67 to -2.40)
Statistical analysis
  • Bulevirtide 2 mg/Day vs Bulevirtide 10 mg/Day · MMRM · p = 0.2977 · Difference in least square (ls) mean: -1.21 · 95% CI -3.50 to 1.08
SecondaryChange From Baseline in Liver Stiffness, as Measured by Elastography at Week 192

MMRM was used for analysis.

Time frame:
Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 192
Reported as:
Least squares mean · kPa
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 192
kPaBulevirtide 2 mg/DayBulevirtide 10 mg/DayDelayed Treatment/Bulevirtide 10 mg/Day
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 192-3.74 (-5.28 to -2.20)-3.70 (-5.27 to -2.14)-1.91 (-3.49 to -0.34)
Statistical analysis
  • Bulevirtide 2 mg/Day vs Bulevirtide 10 mg/Day · MMRM · p = 0.9719 (P-value was based on the mixed-effects model for repeated measurements (MMRM) model.) · Ls-mean of diffrence: -0.04 · 95% CI -2.23 to 2.15Least squares (LS) means, standard errors (SE), 95% CIs and p-values were based on the mixed-effects model for repeated measurements (MMRM) model for change from baseline.
SecondaryChange From Baseline in Liver Stiffness, as Measured by Elastography at Week 240

MMRM was used for analysis.

Time frame:
Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 240
Reported as:
Least squares mean · kPa
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 240
kPaBulevirtide 2 mg/DayBulevirtide 10 mg/DayDelayed Treatment/ Bulevirtide 10 mg/Day
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 240-1.20 (-3.71 to 1.31)-3.31 (-5.78 to -0.84)-3.59 (-6.14 to -1.04)
Statistical analysis
  • Bulevirtide 2 mg/Day vs Bulevirtide 10 mg/Day · MMRM · p = 0.2369 · Ls-mean of difference: 2.11 · 95% CI -1.41 to 5.63Least squares (LS) means, standard errors (SE), 95% CIs and p-values were based on the mixed-effects model for repeated measurements (MMRM) model for change from baseline.
SecondaryPercentage of Participants With Undetectable HDV RNA 24 Weeks After Scheduled End of Treatment (Sustained Virological Response)

Undetectable HDV RNA 24 Weeks after Scheduled End of Treatment means undetectable (\< LLOQ, target not detected) HDV RNA at Week 168

Time frame:
Week 168
Reported as:
Number · percentage of participants
Percentage of Participants With Undetectable HDV RNA 24 Weeks After Scheduled End of Treatment (Sustained Virological Response)
percentage of participantsBulevirtide 2 mg/DayBulevirtide 10 mg/DayDelayed Treatment/Bulevirtide 10 mg/Day
Percentage of Participants With Undetectable HDV RNA 24 Weeks After Scheduled End of Treatment (Sustained Virological Response)18.4 (8.8 to 32.0)26.0 (14.6 to 40.3)18.0 (8.6 to 31.4)
Statistical analysis
  • Bulevirtide 2 mg/Day vs Bulevirtide 10 mg/Day · Fisher Exact · p = 0.4695 (P-value was based on Fisher's Exact Test.) · Response rate difference: 7.6 · 95% CI -9.6 to 24.4For response rate difference, the 95% exact unconditional confidence interval (CI) based on the score statistic was presented.
  • Bulevirtide 2 mg/Day vs Delayed Treatment/Bulevirtide 10 mg/Day · Fisher Exact · p = 1.0000 (P-value was based on Fisher's Exact Test.) · Response rate difference: -0.4 · 95% CI -16.3 to 15.5For response rate difference, the 95% exact unconditional confidence interval (CI) based on the score statistic was presented
SecondaryPercentage of Participants With Undetectable HDV RNA 48 Weeks After Scheduled End of Treatment (Sustained Virological Response)

Undetectable HDV RNA 48 Weeks after Scheduled End of Treatment means undetectable (\< LLOQ, target not detected) HDV RNA at Week 192

Time frame:
Week 192
Reported as:
Number · percentage of participants
Percentage of Participants With Undetectable HDV RNA 48 Weeks After Scheduled End of Treatment (Sustained Virological Response)
percentage of participantsBulevirtide 2 mg/DayBulevirtide 10 mg/DayDelayed Treatment/Bulevirtide 10 mg/Day
Percentage of Participants With Undetectable HDV RNA 48 Weeks After Scheduled End of Treatment (Sustained Virological Response)16.3 (7.3 to 29.7)24.0 (13.1 to 38.2)16.0 (7.2 to 29.1)
Statistical analysis
  • Bulevirtide 2 mg/Day vs Bulevirtide 10 mg/Day · Fisher Exact · p = 0.4539 (P-value was based on Fisher's Exact Test.) · Response rate difference: 7.7 · 95% CI -8.8 to 24.0For response rate difference, the 95% exact unconditional confidence interval (CI) based on the score statistic was presented
  • Bulevirtide 2 mg/Day vs Delayed Treatment/Bulevirtide 10 mg/Day · Fisher Exact · p = 1.0000 (P-value was based on Fisher's Exact Test.) · Response rate difference: -0.3 · 95% CI -15.6 to 15.5For response rate difference, the 95% exact unconditional confidence interval (CI) based on the score statistic was presented.
SecondaryPercentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event (AE) by Week 144

An AE was defined as any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.

Time frame:
Delayed Treatment/Bulevirtide 10 mg/day arm: Week 48 up to Week 144; Bulevirtide 2mg/day and 10 mg/day arms: First dose date up to Week 144
Reported as:
Number · percentage of participants
Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event (AE) by Week 144
percentage of participantsBulevirtide 2 mg/DayBulevirtide 10 mg/DayDelayed Treatment/Bulevirtide 10 mg/Day
Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event (AE) by Week 144000

Adverse events

Collected over All-Cause Mortality: Up to Week 240; Adverse Events: Up to Week 48 (first 3 arms); Up to Week 144 (arms 4 and 5); Up to Weeks 48-144 (arm 6); >Week 144 up to Week 240 (arms 7-9). Adverse Event: SAS included all participants randomized (posttreatment SAS required >=1 measurement after EOT) delayed treatment arm or randomized to bulevirtide and received bulevirtide at least once after randomization. All-cause mortality: Randomized Set included all enrolled and randomized participants.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Delayed Treatment (Baseline to Week 48)0/51 (0%)1/51 (2%)30/51 (58.8%)
Bulevirtide 2 mg/Day (Baseline to Week 48)0/49 (0%)2/49 (4.1%)35/49 (71.4%)
Bulevirtide 10 mg/Day (Baseline to Week 48)0/50 (0%)1/50 (2%)41/50 (82%)
Bulevirtide 2 mg/Day (Baseline to Week 144)0/49 (0%)3/49 (6.1%)44/49 (89.8%)
Bulevirtide 10 mg/Day (Baseline to Week 144)0/50 (0%)6/50 (12%)46/50 (92%)
Delayed Treatment/Bulevirtide 10 mg/Day (Week 48 to Week 144)1/50 (2%)3/50 (6%)41/50 (82%)
Bulevirtide 2 mg/Day (After EOT (>Week 144 up to Week 240))0/46 (0%)7/46 (15.2%)31/46 (67.4%)
Bulevirtide 10 mg/Day (After EOT (>Week 144 up to Week 240)0/47 (0%)7/47 (14.9%)33/47 (70.2%)
Delayed Treatment/Bulevirtide 10 mg/Day (After EOT (>Week 144 up to Week 240)0/49 (0%)8/49 (16.3%)34/49 (69.4%)
Most frequent serious events
Showing 10 of 29
Most frequent serious events
EventDelayed Treatment (Baseline to Week 48)Bulevirtide 2 mg/Day (Baseline to Week 48)Bulevirtide 10 mg/Day (Baseline to Week 48)Bulevirtide 2 mg/Day (Baseline to Week 144)Bulevirtide 10 mg/Day (Baseline to Week 144)Delayed Treatment/Bulevirtide 10 mg/Day (Week 48 to Week 144)Bulevirtide 2 mg/Day (After EOT (>Week 144 up to Week 240))Bulevirtide 10 mg/Day (After EOT (>Week 144 up to Week 240)Delayed Treatment/Bulevirtide 10 mg/Day (After EOT (>Week 144 up to Week 240)
Hepatitis DInfections and infestations0/510/490/500/490/500/504/464/472/49
Covid-19 pneumoniaInfections and infestations0/510/491/500/492/500/500/460/470/49
AnaemiaBlood and lymphatic system disorders0/510/490/500/490/500/501/460/470/49
Oesophageal varices haemorrhageGastrointestinal disorders0/510/490/500/490/500/501/460/470/49
Hepatitis acuteHepatobiliary disorders0/510/490/500/490/500/501/460/470/49
Hepatocellular carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/510/490/500/490/500/501/460/470/49
Alanine aminotransferase increasedInvestigations0/510/490/500/490/500/500/461/471/49
Transaminases increasedInvestigations0/510/490/500/490/500/500/461/471/49
Facial paralysisNervous system disorders0/510/490/500/490/500/500/461/470/49
Varices oesophagealGastrointestinal disorders0/510/490/501/490/500/500/460/470/49
Most frequent other events
Showing 10 of 51
Most frequent other events
EventDelayed Treatment (Baseline to Week 48)Bulevirtide 2 mg/Day (Baseline to Week 48)Bulevirtide 10 mg/Day (Baseline to Week 48)Bulevirtide 2 mg/Day (Baseline to Week 144)Bulevirtide 10 mg/Day (Baseline to Week 144)Delayed Treatment/Bulevirtide 10 mg/Day (Week 48 to Week 144)Bulevirtide 2 mg/Day (After EOT (>Week 144 up to Week 240))Bulevirtide 10 mg/Day (After EOT (>Week 144 up to Week 240)Delayed Treatment/Bulevirtide 10 mg/Day (After EOT (>Week 144 up to Week 240)
Vitamin D deficiencyMetabolism and nutrition disorders13/517/497/5022/4919/5014/506/467/477/49
Alanine aminotransferase increasedInvestigations4/512/493/505/494/500/5019/4611/4718/49
Aspartate aminotransferase increasedInvestigations3/511/491/502/491/501/5017/4611/4715/49
HeadacheNervous system disorders0/519/4910/5010/4912/507/500/461/471/49
LeukopeniaBlood and lymphatic system disorders10/517/495/5010/499/507/502/464/475/49
ThrombocytopeniaBlood and lymphatic system disorders8/515/495/5010/498/507/506/465/477/49
NeutropeniaBlood and lymphatic system disorders3/512/495/508/4910/503/503/464/473/49
FatigueGeneral disorders1/515/497/507/499/503/500/465/474/49
Gamma-glutamyltransferase increasedInvestigations1/510/492/501/493/502/508/464/473/49
LymphopeniaBlood and lymphatic system disorders4/514/494/508/496/505/503/464/477/49

Baseline characteristics

The Full Analysis Set (FAS) included all participants who were randomized to bulevirtide and took at least 1 dose of bulevirtide and those who were randomized to delayed treatment group.

Age, Categorical
Age, Categorical(Participants)Delayed Treatment/Bulevirtide 10 mg/DayBulevirtide 2 mg/DayBulevirtide 10 mg/DayTotal
<=18 years0000
Between 18 and 65 years514950150
>=65 years0000
Age, Continuous
Age, Continuous(years)Delayed Treatment/Bulevirtide 10 mg/DayBulevirtide 2 mg/DayBulevirtide 10 mg/DayTotal
Mean41 ± 7.544 ± 9.041 ± 8.542 ± 8.4
Sex: Female, Male
Sex: Female, Male(Participants)Delayed Treatment/Bulevirtide 10 mg/DayBulevirtide 2 mg/DayBulevirtide 10 mg/DayTotal
Female25192064
Male26303086
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Delayed Treatment/Bulevirtide 10 mg/DayBulevirtide 2 mg/DayBulevirtide 10 mg/DayTotal
American Indian or Alaska Native0000
Asian118625
Native Hawaiian or Other Pacific Islander0000
Black or African American0011
White404143124
More than one race0000
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(Participants)Delayed Treatment/Bulevirtide 10 mg/DayBulevirtide 2 mg/DayBulevirtide 10 mg/DayTotal
Germany761427
Italy711624
Russia29282885
Sweden84214
Hepatitis Delta Virus (HDV) Ribonucleic Acid (RNA)
Hepatitis Delta Virus (HDV) Ribonucleic Acid (RNA)(log10 IU/mL)Delayed Treatment/Bulevirtide 10 mg/DayBulevirtide 2 mg/DayBulevirtide 10 mg/DayTotal
Mean5.08 ± 1.3585.10 ± 1.1944.96 ± 1.4615.04 ± 1.336
Liver stiffness
Liver stiffness(kPa)Delayed Treatment/Bulevirtide 10 mg/DayBulevirtide 2 mg/DayBulevirtide 10 mg/DayTotal
Mean15.3 ± 8.9514.0 ± 8.1914.8 ± 9.2614.7 ± 8.77
08

Study locations

19 sites
  • New York University School of Medicine, an administrative unit of New York University, an education corporation
    New York, New York 10016, United States
  • Cornell University Well Madical College
    New York, New York 10021, United States
  • Universitätsklinikum Essen (AoR), Klinik für Gastroenterologie und Hepatologie
    Essen, Germany
  • Universitätsklinikum Frankfurt Medizinische Klinik 1
    Frankfurt am Main, Germany
  • Universitätsklinikum Hamburg-Eppendorf
    Hamburg, Germany
  • Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie
    Hanover, Germany
  • Heidelberg University Hospital, Departament of Gastroenterology, Infectious Diseases, Intoxication
    Heidelberg, Germany
  • Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
    Milan, Italy
  • Università di Modena e Reggio Emilia- Ospedale Civile S.
    Modena, Italy
  • U.O. Epatologia - Azienda Ospedaliero Universitaria Pisana
    Pisa, Italy
  • State Budgetary Educational Institution of Higher Professional Education "South Ural State Medical University" of the Ministry of Healthcare of the Russian Federation
    Chelyabinsk, Russia
  • Specialized clinical Infectious diseases Hospital
    Krasnodar, Russia
  • Federal Budget Institution of Science "Central Research Institute of Epidemiology" of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance
    Moscow, Russia
  • Federal State Budgetary Institution National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation
    Moscow, Russia
  • LLC"Clinic of Modern Medicine"
    Moscow, Russia
  • Moscow Regional Scientific and Research Clinical Institute
    Moscow, Russia
  • LLC Medical Company "Hepatolog"
    Samara, Russia
  • Stavropol Regional Hospital
    Stavropol, Russia
  • Karolinska University Hospital Huddinge, Dept of Infectious Diseases
    Stockholm, Sweden
09

References and documents

Publications

  • Wedemeyer H, Aleman S, Andreone P, Blank A, Brunetto M, Bogomolov P, et al. Bulevirtide Monotherapy at Low and High Doses in Patients With Chronic Hepatitis Delta: 24 Weeks Interim Data of the Phase 3 MYR301 Study [Poster 2730]. European Association for the Study of the Liver (EASL): The Digital International Liver Congress; 2021 23-26 June.
  • Wedemeyer H, Aleman S, Brunetto M, Blank A, Andreone P, Bogomolov P, et al. Efficacy and Safety of Bulevirtide Monotherapy Given at 2 mg or 10 mg Dose Level Once Daily for Treatment of Chronic Hepatitis Delta: Week 48 Primary Endpoint Results From a Phase 3 Randomized, Multicenter, Parallel Design Study [Oral Presentation 509]. EASL The International Liver Congress; 2022 22-26 June; London, UK.
  • Lampertico P, Roulot D, Wedemeyer H. Bulevirtide with or without pegIFNalpha for patients with compensated chronic hepatitis delta: From clinical trials to real-world studies. J Hepatol. 2022 Nov;77(5):1422-1430. doi: 10.1016/j.jhep.2022.06.010. Epub 2022 Jun 22. PubMed 35752223 ↗
  • Wedemeyer H, Aleman S, Brunetto M, Blank A, Andreone P, Bogomolov P, et al. Efficacy and Safety at 96 weeks of Bulevirtide 2 mg or 10 mg Monotherapy for Chronic Hepatitis D: Results From an Interim Analysis of a Phase 3 Randomized Study. [Oral Presentation OS-068]. EASL The International Liver Congress; 2023 21-24 June; Vienna, AUS.
  • Wedemeyer H, Aleman S, Brunetto MR, Blank A, Andreone P, Bogomolov P, Chulanov V, Mamonova N, Geyvandova N, Morozov V, Sagalova O, Stepanova T, Berger A, Manuilov D, Suri V, An Q, Da B, Flaherty J, Osinusi A, Liu Y, Merle U, Schulze Zur Wiesch J, Zeuzem S, Ciesek S, Cornberg M, Lampertico P; MYR 301 Study Group. A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D. N Engl J Med. 2023 Jul 6;389(1):22-32. doi: 10.1056/NEJMoa2213429. Epub 2023 Jun 22. PubMed 37345876 ↗
  • Wedemeyer H, Aleman S, Brunetto M, Blank A, Andreone P, Bogomolov P, Chulanov V, Mamonova N, Geyvandova N, Morozov V, Sagalova O, Stepanova T, Berger A, Ciesek S, Manuilov D, Mercier RC, Da BL, Chee GM, Li M, Flaherty JF, Lau AH, Osinusi A, Schulze Zur Wiesch J, Cornberg M, Zeuzem S, Lampertico P. Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial. J Hepatol. 2024 Oct;81(4):621-629. doi: 10.1016/j.jhep.2024.05.001. Epub 2024 May 9. PubMed 38734383 ↗
  • Aleman S, Brunetto M, Blank A et al. Efficacy and Safety of Bulevirtide Monotherapy for Chronic Hepatitis Delta: Posttreatment Results Through 48 Weeks After the End of Treatment From an Interim Analysis of a Randomized Phase 3 Study, MYR301; The Liver Meeting, American Association for the Study of Liver Diseases; 2024 15-19 November; San Diego, USA.
  • Wedemeyer H, Aleman S, Blank A et al. Final results of MYR301: A Randomised Phase 3 Study Evaluating the Efficacy and Safety of up to 144 Weeks of Bulevirtide Monotherapy For Chronic Hepatitis Delta and 96 Weeks of Posttreatment Follow-up. EASL The International Liver Congress; 2025 7-10 May, Amsterdam, Netherlands.
  • Wedemeyer H, Aleman S, Blank A, Andreone P, Bogomolov P, Chulanov V, Mamonova N, Geyvandova N, Morozov V, Sagalova O, Stepanova T, Berger A, Ciesek S, Lichtman A, Manuilov D, Mercier RC, Arterburn S, Christian-Cox F, Tseng S, Osinusi A, Schulze Zur Wiesch J, Cornberg M, Zeuzem S, Brunetto MR, Lampertico P. 144 Weeks of bulevirtide monotherapy for chronic hepatitis D: Final and posttreatment results from a Phase 3 randomized trial. J Hepatol. 2026 Apr 9:S0168-8278(26)00201-1. doi: 10.1016/j.jhep.2026.03.046. Online ahead of print. PubMed 41966308 ↗
  • Wong RJ, Gish RG, Jacobson IM, Lim JK, Rock M, Kinyik-Merena C, Ma H, Smith N, Kim C. Impact of Double Reflex Testing and Linkage to Treatment on Clinical Outcomes of Chronic Hepatitis Delta Virus Infection in the United States. J Viral Hepat. 2026 Jan;33(1):e70119. doi: 10.1111/jvh.70119. PubMed 41405233 ↗
  • Asselah T, Lampertico P, Aleman S, Bourliere M, Streinu-Cercel A, Bogomolov P, Morozov V, Stepanova T, Lazar S, Manuilov D, Mercier RC, Tseng S, Ye L, Flaherty JF, Osinusi A, Da BL, Chee GM, Lau AH, Brunetto MR, Wedemeyer H. Bulevirtide Monotherapy Is Safe and Well Tolerated in Chronic Hepatitis Delta: An Integrated Safety Analysis of Bulevirtide Clinical Trials at Week 48. Liver Int. 2025 Apr;45(4):e16174. doi: 10.1111/liv.16174. Epub 2024 Dec 8. PubMed 39648559 ↗
  • Buti M, Wedemeyer H, Aleman S, Chulanov V, Morozov V, Sagalova O, Stepanova T, Gish RG, Lloyd A, Kaushik AM, Suri V, Manuilov D, Osinusi AO, Flaherty JF, Lampertico P. Patient-reported outcomes in chronic hepatitis delta: An exploratory analysis of the phase III MYR301 trial of bulevirtide. J Hepatol. 2025 Jan;82(1):28-36. doi: 10.1016/j.jhep.2024.06.031. Epub 2024 Jul 14. PubMed 39009085 ↗
  • Allweiss L, Volmari A, Suri V, Wallin JJ, Flaherty JF, Manuilov D, Downie B, Lutgehetmann M, Bockmann JH, Urban S, Wedemeyer H, Dandri M. Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies. J Hepatol. 2024 Jun;80(6):882-891. doi: 10.1016/j.jhep.2024.01.035. Epub 2024 Feb 8. PubMed 38340811 ↗
  • Hollnberger J, Liu Y, Xu S, Chang S, Martin R, Manhas S, Aeschbacher T, Han B, Yazdi T, May L, Han D, Shornikov A, Flaherty J, Manuilov D, Suri V, Asselah T, Lampertico P, Wedemeyer H, Aleman S, Richards C, Mateo R, Maiorova E, Cihlar T, Mo H, Urban S. No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta. J Hepatol. 2023 Sep;79(3):657-665. doi: 10.1016/j.jhep.2023.04.027. Epub 2023 Apr 27. PubMed 37120031 ↗

Study documents

  • Study protocol · Apr 25, 2022
  • Study protocol · Jan 25, 2023
  • Statistical analysis plan · Aug 20, 2021
  • Statistical analysis plan · Oct 25, 2022
  • Statistical analysis plan · Jun 26, 2023
  • Statistical analysis plan · Feb 5, 2024
  • Statistical analysis plan · Nov 15, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 22, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03852719
Lead sponsor
Gilead Sciences
Responsible party
Sponsor
First posted
Feb 25, 2019
Start date
Apr 17, 2019
Primary completion
Nov 26, 2020
Completion
Aug 8, 2024
Results posted
Oct 28, 2022
Last update
Aug 22, 2025

Study contacts

Gilead Medical Monitor
study chair · Gilead Sciences

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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