Hepatitis C, Chronic
Conditions
Brief summary
The main purpose of this study is to evaluate the safety and tolerability of a combination treatment of AL-335, odalasvir (ODV), and simeprevir (SMV) for 8 weeks in Japanese participants with genotype 1 or 2 chronic hepatitis C virus (HCV) infection without cirrhosis and for 12 weeks in direct-acting antiviral (DAA)-naive Japanese participants with genotype 1 or 2 chronic HCV infection with compensated cirrhosis.
Interventions
DRUGAL-335
Participants will receive AL-335 800 mg once daily for 8 weeks in cohort 1 and 12 weeks in cohort 2.
DRUGOdalasvir (ODV)
Participants will receive ODV 25 mg once daily for 8 weeks in cohort 1 and 12 weeks in cohort 2.
DRUGSimeprevir (SMV)
Participants will receive SMV 75 mg once daily for 8 weeks in cohort 1 and 12 weeks in cohort 2.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis C virus (HCV) infection * All participants must have HCV genotype 1 or 2 infection, determined at screening * HCV ribonucleic acid (RNA) plasma levels greater than or equal to (\>=)10,000 international units per Milliliter (IU/mL), determined at screening * Direct-acting antiviral (DAA)-naive participants, defined as not having received treatment with any approved or investigational DAA drug for chronic HCV infection; prior HCV therapy consisting of interferon (IFN, pegylated or nonpegylated) with or without ribavirin (RBV) is allowed * Participants without cirrhosis or with compensated cirrhosis
Exclusion criteria
* Infection with HCV genotype - 3, 4, 5, or 6 * Co-infection with human immunodeficiency virus (HIV 1 or HIV 2 antibody positive) or hepatitis B virus (HBV) (hepatitis B surface antigen \[HBsAg\] positive) * Prior treatment with any investigational or approved HCV DAA, either in combination with PegIFN or IFN free * Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection (immunoglobulin M), drug or alcohol related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha 1 antitrypsin deficiency, primary biliary cirrhosis, or any other non-HCV liver disease that is considered clinically significant by the investigator * Evidence of hepatic decompensation as assessed with Child-Pugh Class B or C or any of the following: history or current clinical evidence of ascites, bleeding varices, or hepatic encephalopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Approximately 38 weeks (Cohort 1) and 42 weeks (Cohort 2) | An adverse event was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) After Actual End-of-treatment | Week 12 (follow-up phase) | SVR12 was defined as HCV RNA \< LLOQ (15 IU/mL) detected or not detected at 12 weeks after the actual EOT. |
| Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) After Actual End-of-treatment | Week 24 (follow-up phase) | SVR 24 was defined as HCV RNA \< LLOQ (15 IU/mL) detected or not detected at 24 weeks after the actual EOT. |
| Percentage of Participants With Viral Relapse | End of treatment up to Week 24 (follow up phase) | Viral relapse was defined as participants who did not achieve SVR12, with HCV RNA \< LLOQ (15 IU/mL) at the EOT and confirmed HCV RNA greater than or equal to (\>=) LLOQ during follow-up. |
| Percentage of Participants With Sustained Virologic Response 4 Weeks (SVR4) After Actual End-of-Treatment | Week 4 (follow-up phase) | SVR4 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detected or not detected at 4 weeks after the actual End-of-treatment (EOT). |
| Percentage of Participants With On-treatment Virologic Response | Day 2, Day 3, Week 1, 2, 3, 4, 6, 8 (for Cohort 1), 10, and 12 (for Cohort 2 only) | Percentage of participants with On-treatment Virologic Response with HCV RNA \< LLOQ (15 IU/mL), not detected at specified time points during treatment were reported. |
| Time to Achieve HCV RNA Not Detected or HCV RNA <LLOQ | EOT up to Week 24 (follow up phase) | Time to Achieve HCV RNA not Detected or HCV RNA \<LLOQ (15 IU/mL) was reported. |
| Percentage of Participants With On-treatment Failure | EOT up to Week 12 (follow up phase) | On-treatment failure was defined as participants who did not achieve SVR12, with confirmed HCV RNA \>= LLOQ (15 IU/mL) at the actual EOT. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis Participants received AL-335 800 milligram (mg) (2\*400) tablets, odalasvir (ODV) 25 mg tablet and simeprevir (SMV) 75 mg capsule once daily orally for 8 weeks. | 22 |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis Participants received AL-335 800 mg (2\*400) tablets, ODV 25 mg tablet and SMV 75 mg capsule once daily orally for 12 weeks. | 11 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: Chronic Hepatitis C Without Cirrhosis | Total | Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis |
|---|---|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 11.1 | 57.8 years STANDARD_DEVIATION 9.98 | 54.9 years STANDARD_DEVIATION 6.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 33 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 33 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 22 Participants | 33 Participants | 11 Participants |
| Sex: Female, Male Female | 17 Participants | 21 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 11 |
| other Total, other adverse events | 15 / 22 | 9 / 11 |
| serious Total, serious adverse events | 0 / 22 | 1 / 11 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An adverse event was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: Approximately 38 weeks (Cohort 1) and 42 weeks (Cohort 2)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Number of Participants With Adverse Events (AEs) | 15 participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Number of Participants With Adverse Events (AEs) | 9 participants |
Secondary
Percentage of Participants With On-treatment Failure
On-treatment failure was defined as participants who did not achieve SVR12, with confirmed HCV RNA \>= LLOQ (15 IU/mL) at the actual EOT.
Time frame: EOT up to Week 12 (follow up phase)
Population: Full analysis set included all enrolled participants who received at least 1 dose of study drug (that is AL-335, ODV or SMV) and had at least 1 postbaseline efficacy measurement in this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With On-treatment Failure | 0 Percentage of Participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Failure | 0 Percentage of Participants |
Secondary
Percentage of Participants With On-treatment Virologic Response
Percentage of participants with On-treatment Virologic Response with HCV RNA \< LLOQ (15 IU/mL), not detected at specified time points during treatment were reported.
Time frame: Day 2, Day 3, Week 1, 2, 3, 4, 6, 8 (for Cohort 1), 10, and 12 (for Cohort 2 only)
Population: Full analysis set included all enrolled participants who received at least 1 dose of study drug (that is AL-335, ODV or SMV) and had at least 1 postbaseline efficacy measurement in this study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With On-treatment Virologic Response | week 4: < 15 IU/mL not detected | 72.7 Percentage of participants |
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 2: < 15 IU/mL not detected | 22.7 Percentage of participants |
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 6: < 15 IU/mL not detected | 90.9 Percentage of participants |
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 1: < 15 IU/mL not detected | 4.5 Percentage of participants |
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 8: < 15 IU/mL not detected | 100 Percentage of participants |
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 3: < 15 IU/mL not detected | 54.5 Percentage of participants |
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Day 3: < 15 IU/mL not detected | 4.5 Percentage of participants |
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Day 2: < 15 IU/mL not detected | 4.5 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 8: < 15 IU/mL not detected | 100 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 10: < 15 IU/mL not detected | 100 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 12: < 15 IU/mL not detected | 100 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Day 2: < 15 IU/mL not detected | 0 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Day 3: < 15 IU/mL not detected | 0 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 1: < 15 IU/mL not detected | 18.2 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 2: < 15 IU/mL not detected | 45.5 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 3: < 15 IU/mL not detected | 63.6 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | week 4: < 15 IU/mL not detected | 72.7 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With On-treatment Virologic Response | Week 6: < 15 IU/mL not detected | 100 Percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) After Actual End-of-treatment
SVR12 was defined as HCV RNA \< LLOQ (15 IU/mL) detected or not detected at 12 weeks after the actual EOT.
Time frame: Week 12 (follow-up phase)
Population: Full analysis set included all enrolled participants who received at least 1 dose of study drug (that is AL-335, ODV or SMV) and had at least 1 postbaseline efficacy measurement in this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) After Actual End-of-treatment | 100 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) After Actual End-of-treatment | 100 Percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) After Actual End-of-treatment
SVR 24 was defined as HCV RNA \< LLOQ (15 IU/mL) detected or not detected at 24 weeks after the actual EOT.
Time frame: Week 24 (follow-up phase)
Population: Full analysis set included all enrolled participants who received at least 1 dose of study drug (that is AL-335, ODV or SMV) and had at least 1 postbaseline efficacy measurement in this study. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) After Actual End-of-treatment | 100 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) After Actual End-of-treatment | 90.9 Percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 4 Weeks (SVR4) After Actual End-of-Treatment
SVR4 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detected or not detected at 4 weeks after the actual End-of-treatment (EOT).
Time frame: Week 4 (follow-up phase)
Population: Full analysis set included all enrolled participants who received at least 1 dose of study drug (that is AL-335, ODV or SMV) and had at least 1 postbaseline efficacy measurement in this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With Sustained Virologic Response 4 Weeks (SVR4) After Actual End-of-Treatment | 100 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With Sustained Virologic Response 4 Weeks (SVR4) After Actual End-of-Treatment | 100 Percentage of participants |
Secondary
Percentage of Participants With Viral Relapse
Viral relapse was defined as participants who did not achieve SVR12, with HCV RNA \< LLOQ (15 IU/mL) at the EOT and confirmed HCV RNA greater than or equal to (\>=) LLOQ during follow-up.
Time frame: End of treatment up to Week 24 (follow up phase)
Population: Full analysis set included all enrolled participants who received at least 1 dose of study drug (that is AL-335, Odalasvir (ODV) or Simeprevir (SMV)\] and had at least 1 postbaseline efficacy measurement in this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Percentage of Participants With Viral Relapse | 0 Percentage of participants |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Percentage of Participants With Viral Relapse | 0 Percentage of participants |
Secondary
Time to Achieve HCV RNA Not Detected or HCV RNA <LLOQ
Time to Achieve HCV RNA not Detected or HCV RNA \<LLOQ (15 IU/mL) was reported.
Time frame: EOT up to Week 24 (follow up phase)
Population: Full analysis set included all enrolled participants who received at least 1 dose of study drug (that is AL-335, ODV or SMV) and had at least 1 postbaseline efficacy measurement in this study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | Time to Achieve HCV RNA Not Detected or HCV RNA <LLOQ | 19.0 Days | Standard Deviation 1.68 |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | Time to Achieve HCV RNA Not Detected or HCV RNA <LLOQ | 18.6 Days | Standard Deviation 3.86 |