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Efficacy and Safety of Combinations of AL-335, Odalasvir (ODV) and Simeprevir (SMV) in the Treatment of Chronic Hepatitis C Infection

A Phase 2b, Multicenter, Randomized, Open-label Study to Investigate the Efficacy, Safety and Pharmacokinetics of Different Treatment Regimens of AL-335, Odalasvir, and Simeprevir in Treatment-naive and Treatment-experienced Subjects With Chronic Hepatitis C Virus Genotype 1, 2, 4, 5, and 6 Infection Without Cirrhosis

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02765490
Enrollment
365
Registered
2016-05-06
Start date
2016-11-09
Completion date
2017-11-16
Last updated
2019-11-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C, Chronic, AL-335, Odalasvir, Simeprevir, ODV, SMV, ACH-3102, ACH-0143102, TMC435

Brief summary

The purpose of this study is to evaluate the efficacy (proportion of subjects with SVR12), safety, tolerability and pharmacokinetics of an 8- and 6-week treatment regimen of AL-335, odalasvir (ODV) and simeprevir (SMV) in chronic HCV genotype 1, 2, 4, 5 or 6 infected subjects without cirrhosis.

Detailed description

This is a Phase 2b multicenter study. The study will include a screening period of maximum 6 weeks, a treatment period of 6 or 8 weeks and a 24-weeks post-treatment follow-up period. The total study duration for each subject will be 36 to 38 weeks. This study investigates a 3 direct-acting antiviral agent (DAA) combination of AL-335 (HCV NS5B inhibitor), odalasvir (ODV) (a second generation HCV NS5A inhibitor) and simeprevir (SMV) (HCV NS3A4 protease inhibitor). The results of this study will enable the selection of treatment and duration to be further developed.

Interventions

DRUGAL-335

AL-335 800 mg (2\*400) tablet will be administered once daily.

DRUGOdalasvir

Odalasvir 25 mg tablet will be administered once daily.

DRUGSimeprevir

Simeprevir 75 mg capsule will be administered once daily.

Sponsors

Janssen Research & Development, LLC
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No

Inclusion criteria

* Individuals with chronic hepatitis C virus (HCV) genotype 1, 2, 4, 5 or 6 infection * Documented as treatment naive or experienced with a prior regimen consisting of Interferon (IFN) +/-Ribavirin (RBV) regimen without achieving sustained viral response * Absence of cirrhosis * Screening laboratory values within defined thresholds * Must use specific contraceptive methods if female of childbearing potential or sexually active male

Exclusion criteria

* Co-infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) * Prior exposure to an HCV direct-acting antiviral agent (DAA), either in combination with pegylated interferon (PegIFN) or IFN-free * Current or prior history of clinical hepatic decompensation * History of clinically significant illness or any other medical disorder including cardiovascular conditions that may interfere with individual's treatment, assessment or compliance with the protocol * Pregnant or a nursing female

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)Week 12 (Follow-Up Phase)The SVR 12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable 12 weeks after actual EOT.

Secondary

MeasureTime frameDescription
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)Week 24 (Follow-Up Phase)The SVR24 was defined as HCV RNA \<LLOQ (detectable or undetectable) 24 weeks after End of Treatment (EOT).
Number of Participants With Viral RelapseEnd of Treatment up to Week 24 (Follow up phase)Viral Relapse: Participants who did not achieve SVR12, with HCV RNA \<LLOQ at the EOT and confirmed HCV RNA greater than or equal to (\>=) LLOQ during follow-up.
Number of Participants With Late Viral RelapseUp to Week 24 (Follow-up Phase)Late Viral Relapse: Participants who achieved SVR12 but had confirmed HCV RNA\>=LLOQ afterwards during follow-up.
Percentage of Participants With On-treatment FailureEOT up to Week 12 (Follow up Phase)On-treatment failure: Participants who did not achieve SVR12 and with confirmed HCV RNA\>=LLOQ at the End of Treatment (EOT).
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Treatment (EOT)Week 4 (Follow-Up Phase)The SVR 4 was defined as participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was \<LLOQ (detectable or undetectable).

Countries

Belgium, Canada, Germany, Poland, Singapore, Spain

Participant flow

Participants by arm

ArmCount
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
183
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
182
Total365

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyDeath01
Overall StudyLost to Follow-up11
Overall StudyOther01

Baseline characteristics

CharacteristicArm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 WeeksTotalArm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
Age, Continuous49 years49 years48 years
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
14 Participants23 Participants9 Participants
Race (NIH/OMB)
Black or African American
10 Participants19 Participants9 Participants
Race (NIH/OMB)
More than one race
2 Participants2 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Unknown or Not Reported
3 Participants6 Participants3 Participants
Race (NIH/OMB)
White
153 Participants314 Participants161 Participants
Region of Enrollment
Belgium
35 Participants81 Participants46 Participants
Region of Enrollment
Canada
30 Participants63 Participants33 Participants
Region of Enrollment
Germany
17 Participants32 Participants15 Participants
Region of Enrollment
Italy
29 Participants53 Participants24 Participants
Region of Enrollment
Poland
29 Participants61 Participants32 Participants
Region of Enrollment
Singapore
11 Participants17 Participants6 Participants
Region of Enrollment
Spain
31 Participants58 Participants27 Participants
Sex: Female, Male
Female
94 Participants182 Participants88 Participants
Sex: Female, Male
Male
88 Participants183 Participants95 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 1831 / 182
other
Total, other adverse events
83 / 18385 / 182
serious
Total, serious adverse events
7 / 1834 / 182

Outcome results

Primary

Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)

The SVR 12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable 12 weeks after actual EOT.

Time frame: Week 12 (Follow-Up Phase)

Population: Intent-To-Treat (ITT) population included all randomized participants who took at least 1 dose of the study drug \[that is AL-335, Odalasvir (ODV) or Simeprevir (SMV)\].

ArmMeasureValue (NUMBER)
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 WeeksPercentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)98.9 Percentage of Participants
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 WeeksPercentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)97.8 Percentage of Participants
Secondary

Number of Participants With Late Viral Relapse

Late Viral Relapse: Participants who achieved SVR12 but had confirmed HCV RNA\>=LLOQ afterwards during follow-up.

Time frame: Up to Week 24 (Follow-up Phase)

Population: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e, AL-335, ODV or SMV).

ArmMeasureValue (NUMBER)
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 WeeksNumber of Participants With Late Viral Relapse0 Participants
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 WeeksNumber of Participants With Late Viral Relapse1 Participants
Secondary

Number of Participants With Viral Relapse

Viral Relapse: Participants who did not achieve SVR12, with HCV RNA \<LLOQ 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: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e, AL-335, ODV or SMV).

ArmMeasureValue (NUMBER)
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 WeeksNumber of Participants With Viral Relapse1 Participants
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 WeeksNumber of Participants With Viral Relapse4 Participants
Secondary

Percentage of Participants With On-treatment Failure

On-treatment failure: Participants who did not achieve SVR12 and with confirmed HCV RNA\>=LLOQ at the End of Treatment (EOT).

Time frame: EOT up to Week 12 (Follow up Phase)

Population: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e, AL-335, ODV or SMV).

ArmMeasureValue (NUMBER)
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 WeeksPercentage of Participants With On-treatment Failure0 Percentage of Participants
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 WeeksPercentage of Participants With On-treatment Failure0 Percentage of Participants
Secondary

Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)

The SVR24 was defined as HCV RNA \<LLOQ (detectable or undetectable) 24 weeks after End of Treatment (EOT).

Time frame: Week 24 (Follow-Up Phase)

Population: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e., AL-335, ODV or SMV). Last Observation Carried Forward (LOCF) method was used to impute the missing values.

ArmMeasureValue (NUMBER)
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 WeeksPercentage of Participants With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)98.9 Percentage of Participants
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 WeeksPercentage of Participants With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)97.3 Percentage of Participants
Secondary

Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Treatment (EOT)

The SVR 4 was defined as participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was \<LLOQ (detectable or undetectable).

Time frame: Week 4 (Follow-Up Phase)

Population: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e, AL-335, ODV or SMV).

ArmMeasureValue (NUMBER)
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 WeeksPercentage of Participants With Sustained Virologic Response 4 Weeks After End of Treatment (EOT)99.5 Percentage of Participants
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 WeeksPercentage of Participants With Sustained Virologic Response 4 Weeks After End of Treatment (EOT)98.4 Percentage of Participants

Source: ClinicalTrials.gov · Data processed: Feb 28, 2026