Hepatitis D, Chronic
Conditions
Brief summary
This single-center, randomized, open-label, pilot study is designed to evaluate the efficacy and safety of 48 weeks of treatment with peginterferon alfa-2a alone versus in combination with ribavirin in participants with CHD.
Interventions
DRUGPeginterferon alfa-2a
Peginterferon alfa-2a will be administered as 180 micrograms (mcg) once weekly via subcutaneous (SC) injection.
DRUGRibavirin
Ribavirin will be administered as 1000 to 1200 milligrams (mg) per day in divided oral doses.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Positive hepatitis B surface antigen (HBsAg) for the prior 6 months * Positive anti-delta for the prior 3 months * Positive HDV RNA at Screening * Elevated ALT (1 to 10 times upper limit of normal) prior to first dose * Chronic, necroinflammatory hepatitis documented within the prior 18 months (non-cirrhotic) or 30 months (cirrhotic) * Negative pregnancy and adequate contraceptive use
Exclusion criteria
* Antiviral therapy for CHD within previous 3 months * Positive for hepatitis A or C, or human immunodeficiency virus (HIV) * Increased risk of metabolic liver disease * Decompensated liver disease * Elevated bilirubin * Poor hematologic or renal function * Drug/alcohol abuse within 1 year prior to study * History of significant psychiatric, autoimmune, pulmonary, cardiac, oncologic, or thyroid disease * Organ transplantation with existing functional graft * Retinopathy or other ophthalmologic complication of diabetes or hypertension * Inclusion in another investigational trial within previous 12 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Alanine Aminotransferase (ALT) Normalization Plus Negative Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) at 48 Weeks After End of Treatment | Week 96 | Normalized ALT was defined as ALT value above the upper limit of normal (ULN) at Baseline with a decrease in ALT value to at/below the ULN at 48 weeks after end of treatment (Week 96). Negative HDV RNA was defined as HDV RNA not detected by polymerase chain reaction (PCR). The number of participants with ALT normalization and negative HDV RNA at Week 96 was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ALT Normalization Plus Negative HDV RNA at End of Treatment | Week 48 | Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at the end of treatment (Week 48). Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with ALT normalization and negative HDV RNA at Week 48 was reported. |
| Number of Participants With ALT Normalization at 48 Weeks After End of Treatment | Week 96 | Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at 48 weeks after end of treatment (Week 96). The number of participants with ALT normalization at Week 96 was reported. |
| Number of Participants With ALT Normalization at End of Treatment | Week 48 | Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at the end of treatment (Week 48). The number of participants with ALT normalization at Week 48 was reported. |
| Number of Participants With Negative HDV RNA at 48 Weeks After End of Treatment | Week 96 | Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with negative HDV RNA at 48 weeks after end of treatment (Week 96) was reported. |
| Number of Participants With Negative HDV RNA at End of Treatment | Week 48 | Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with negative HDV RNA at the end of treatment (Week 48) was reported. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A: Monotherapy With Peginterferon Alfa-2a Participants received peginterferon alfa-2a for 48 weeks as 180 mcg once weekly via SC injection. | 6 |
| Group B: Combination With Peginterferon Alfa-2a + Ribavirin Participants received peginterferon alfa-2a plus ribavirin for 48 weeks. Peginterferon alfa-2a was given as 180 mcg once weekly via SC injection. Ribavirin was administered as 1000 to 1200 mg per day in divided (morning/evening) oral doses. The specific dose was determined according to the participant's body weight at Baseline. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Psychiatric Disorder | 0 | 1 |
| Overall Study | Refused Therapy | 0 | 1 |
Baseline characteristics
| Characteristic | Group A: Monotherapy With Peginterferon Alfa-2a | Group B: Combination With Peginterferon Alfa-2a + Ribavirin | Total |
|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 9.2 | 49.2 years STANDARD_DEVIATION 7.4 | 48.2 years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Alanine Aminotransferase (ALT) Normalization Plus Negative Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) at 48 Weeks After End of Treatment
Normalized ALT was defined as ALT value above the upper limit of normal (ULN) at Baseline with a decrease in ALT value to at/below the ULN at 48 weeks after end of treatment (Week 96). Negative HDV RNA was defined as HDV RNA not detected by polymerase chain reaction (PCR). The number of participants with ALT normalization and negative HDV RNA at Week 96 was reported.
Time frame: Week 96
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Monotherapy With Peginterferon Alfa-2a | Number of Participants With Alanine Aminotransferase (ALT) Normalization Plus Negative Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) at 48 Weeks After End of Treatment | 0 participants |
| Group B: Combination With Peginterferon Alfa-2a + Ribavirin | Number of Participants With Alanine Aminotransferase (ALT) Normalization Plus Negative Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) at 48 Weeks After End of Treatment | 1 participants |
p-value: 0.3Fisher Exact
Secondary
Number of Participants With ALT Normalization at 48 Weeks After End of Treatment
Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at 48 weeks after end of treatment (Week 96). The number of participants with ALT normalization at Week 96 was reported.
Time frame: Week 96
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Monotherapy With Peginterferon Alfa-2a | Number of Participants With ALT Normalization at 48 Weeks After End of Treatment | 3 participants |
| Group B: Combination With Peginterferon Alfa-2a + Ribavirin | Number of Participants With ALT Normalization at 48 Weeks After End of Treatment | 1 participants |
p-value: 0.22Fisher Exact
Secondary
Number of Participants With ALT Normalization at End of Treatment
Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at the end of treatment (Week 48). The number of participants with ALT normalization at Week 48 was reported.
Time frame: Week 48
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Monotherapy With Peginterferon Alfa-2a | Number of Participants With ALT Normalization at End of Treatment | 1 participants |
| Group B: Combination With Peginterferon Alfa-2a + Ribavirin | Number of Participants With ALT Normalization at End of Treatment | 0 participants |
p-value: 0.3Fisher Exact
Secondary
Number of Participants With ALT Normalization Plus Negative HDV RNA at End of Treatment
Normalized ALT was defined as ALT value above the ULN at Baseline with a decrease in ALT value to at/below the ULN at the end of treatment (Week 48). Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with ALT normalization and negative HDV RNA at Week 48 was reported.
Time frame: Week 48
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Monotherapy With Peginterferon Alfa-2a | Number of Participants With ALT Normalization Plus Negative HDV RNA at End of Treatment | 0 participants |
| Group B: Combination With Peginterferon Alfa-2a + Ribavirin | Number of Participants With ALT Normalization Plus Negative HDV RNA at End of Treatment | 0 participants |
Secondary
Number of Participants With Negative HDV RNA at 48 Weeks After End of Treatment
Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with negative HDV RNA at 48 weeks after end of treatment (Week 96) was reported.
Time frame: Week 96
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Monotherapy With Peginterferon Alfa-2a | Number of Participants With Negative HDV RNA at 48 Weeks After End of Treatment | 0 participants |
| Group B: Combination With Peginterferon Alfa-2a + Ribavirin | Number of Participants With Negative HDV RNA at 48 Weeks After End of Treatment | 1 participants |
p-value: 0.3Fisher Exact
Secondary
Number of Participants With Negative HDV RNA at End of Treatment
Negative HDV RNA was defined as HDV RNA not detected by PCR. The number of participants with negative HDV RNA at the end of treatment (Week 48) was reported.
Time frame: Week 48
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Monotherapy With Peginterferon Alfa-2a | Number of Participants With Negative HDV RNA at End of Treatment | 1 participants |
| Group B: Combination With Peginterferon Alfa-2a + Ribavirin | Number of Participants With Negative HDV RNA at End of Treatment | 2 participants |
p-value: 0.5Fisher Exact