Hepatitis C, Liver Disease
Conditions
Keywords
Chronic hepatitis C genotype 2, Chronic hepatitis C genotype 3, Cyclophilin inhibitor, Interferon intolerant
Brief summary
The primary purpose of this study is to evaluate the pharmacodynamic (i.e. hepatitis C virus (HCV) viral load), pharmacokinetic and safety profiles between two treatment groups receiving different doses of DEB025 in combination with ribavirin (RBV) during the first 12 weeks treatment in chronic hepatitis C genotype (GT)-2 and GT-3 patients who had previously failed interferon therapy or were intolerant or unable to take interferon.
Interventions
DRUGAlisporivir
ALV 100 and 200 mg soft gel capsules administered orally
DRUGRibavirin
RBV 200 mg tablets (weight-based dose: \< 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose
Sponsors
Debiopharm International SA
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
1. Written informed consent must be obtained before any assessment is performed 2. Participants with HCV genotype 2 or 3 infection who have previously failed interferon therapy or are intolerant or unable to take interferon 3. Males or females aged ≥18 years 4. Diagnosed Chronic hepatitis C virus infection
Exclusion criteria
1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of that medication before enrollment 2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes 3. Hepatitis B surface antigen (HBsAg) positive 4. Human immunodeficiency virus (HIV) positive Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12 | Baseline, Week 12 | The change in log transformed Hepatitis-C Virus (HCV) Ribonucleic acid (RNA) from baseline to Week 12. |
| Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 | Baseline, Week 12 | ALT levels were assessed as part of clinical chemistry assessments throughout the study as a measure of biochemical liver recovery. A negative change from baseline indicates less liver damage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Rapid Virologic Response (RVR) | 4 weeks | eRVR was defined as serum HCV RNA \< LLOQ after 4 weeks of treatment |
| Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment | Up to 24 weeks posttreatment | SVR is defined as HCV RNA less than the lower limit of quantification (LLOQ), i.e., \<15 IU/mL, at 4 weeks (SVR4), 12 weeks (SVR12), and 24 weeks (SVR24) after treatment, respectively. |
| Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End | Up to 24 weeks | ALT is an enzyme found mostly in the cells of the liver and kidney. When the liver is damaged, ALT is released into the blood. This makes ALT a common test for liver damage, because higher ALT levels may indicate more liver damage. ALT upper limit of normal is commonly considered to be 40 international units per liter (IU/L), so abnormal ALT is above 40 IU/L. |
| Percentage of Participants With End of Treatment Response (ETR) | Up to 24 weeks | ETR was defined as serum HCV RNA \< LLOQ at treatment end (completed or prematurely discontinued). |
| Percentage of Participants With Extended Rapid Virologic Response | 2 weeks | Extended rapid virologic response (eRVR) was defined as serum HCV RNA \< LLOQ after 2 weeks of treatment |
Countries
France, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alisporivir 300 mg BID ALV 300 mg BID with RBV for up to 24 weeks. | 26 |
| Alisporivir 400 mg BID ALV 400 mg BID with RBV for up to 24 weeks. | 26 |
| Total | 52 |
Baseline characteristics
| Characteristic | Alisporivir 300 mg BID | Alisporivir 400 mg BID | Total |
|---|---|---|---|
| Age, Continuous | 53.4 years STANDARD_DEVIATION 8.25 | 54.5 years STANDARD_DEVIATION 7.62 | 53.9 years STANDARD_DEVIATION 7.88 |
| Sex: Female, Male Female | 8 Participants | 12 Participants | 20 Participants |
| Sex: Female, Male Male | 18 Participants | 14 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 26 | 24 / 26 |
| serious Total, serious adverse events | 3 / 26 | 3 / 26 |
Outcome results
Primary
Change From Baseline in Alanine Aminotransferase (ALT) at Week 12
ALT levels were assessed as part of clinical chemistry assessments throughout the study as a measure of biochemical liver recovery. A negative change from baseline indicates less liver damage.
Time frame: Baseline, Week 12
Population: Participants in the safety set with available data at the given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alisporivir 300 mg BID | Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 | Baseline | 77.3 U/L | Standard Deviation 48.57 |
| Alisporivir 300 mg BID | Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 | Change from baseline | -67.4 U/L | Standard Deviation 45.99 |
| Alisporivir 400 mg BID | Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 | Baseline | 67.9 U/L | Standard Deviation 42.94 |
| Alisporivir 400 mg BID | Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 | Change from baseline | -58.2 U/L | Standard Deviation 44.5 |
Primary
Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12
The change in log transformed Hepatitis-C Virus (HCV) Ribonucleic acid (RNA) from baseline to Week 12.
Time frame: Baseline, Week 12
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alisporivir 300 mg BID | Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12 | Baseline | 6.323 log10 IU/mL | Standard Deviation 0.4785 |
| Alisporivir 300 mg BID | Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12 | Change from baseline | -3.935 log10 IU/mL | Standard Deviation 2.3361 |
| Alisporivir 400 mg BID | Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12 | Baseline | 6.343 log10 IU/mL | Standard Deviation 0.6396 |
| Alisporivir 400 mg BID | Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12 | Change from baseline | -3.855 log10 IU/mL | Standard Deviation 2.7506 |
Secondary
Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment
SVR is defined as HCV RNA less than the lower limit of quantification (LLOQ), i.e., \<15 IU/mL, at 4 weeks (SVR4), 12 weeks (SVR12), and 24 weeks (SVR24) after treatment, respectively.
Time frame: Up to 24 weeks posttreatment
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alisporivir 300 mg BID | Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment | SVR4 | 30.8 percentage of participants |
| Alisporivir 300 mg BID | Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment | SVR12 | 19.2 percentage of participants |
| Alisporivir 300 mg BID | Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment | SVR24 | 19.2 percentage of participants |
| Alisporivir 400 mg BID | Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment | SVR4 | 38.5 percentage of participants |
| Alisporivir 400 mg BID | Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment | SVR12 | 26.9 percentage of participants |
| Alisporivir 400 mg BID | Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment | SVR24 | 26.9 percentage of participants |
Secondary
Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End
ALT is an enzyme found mostly in the cells of the liver and kidney. When the liver is damaged, ALT is released into the blood. This makes ALT a common test for liver damage, because higher ALT levels may indicate more liver damage. ALT upper limit of normal is commonly considered to be 40 international units per liter (IU/L), so abnormal ALT is above 40 IU/L.
Time frame: Up to 24 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alisporivir 300 mg BID | Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End | End of Treatment | 73.1 percentage of participants |
| Alisporivir 300 mg BID | Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End | End of Study | 38.5 percentage of participants |
| Alisporivir 400 mg BID | Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End | End of Treatment | 61.5 percentage of participants |
| Alisporivir 400 mg BID | Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End | End of Study | 42.3 percentage of participants |
Secondary
Percentage of Participants With End of Treatment Response (ETR)
ETR was defined as serum HCV RNA \< LLOQ at treatment end (completed or prematurely discontinued).
Time frame: Up to 24 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alisporivir 300 mg BID | Percentage of Participants With End of Treatment Response (ETR) | 46.2 percentage of participants |
| Alisporivir 400 mg BID | Percentage of Participants With End of Treatment Response (ETR) | 50.0 percentage of participants |
Secondary
Percentage of Participants With Extended Rapid Virologic Response
Extended rapid virologic response (eRVR) was defined as serum HCV RNA \< LLOQ after 2 weeks of treatment
Time frame: 2 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alisporivir 300 mg BID | Percentage of Participants With Extended Rapid Virologic Response | 0.0 percentage of participants |
| Alisporivir 400 mg BID | Percentage of Participants With Extended Rapid Virologic Response | 3.8 percentage of participants |
Secondary
Percentage of Participants With Rapid Virologic Response (RVR)
eRVR was defined as serum HCV RNA \< LLOQ after 4 weeks of treatment
Time frame: 4 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alisporivir 300 mg BID | Percentage of Participants With Rapid Virologic Response (RVR) | 3.8 percentage of participants |
| Alisporivir 400 mg BID | Percentage of Participants With Rapid Virologic Response (RVR) | 15.4 percentage of participants |