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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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02765490
First Posted: May 6, 2016
Last Update Posted: December 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Janssen Research & Development, LLC
  Purpose
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.

Condition Intervention Phase
Hepatitis C, Chronic Drug: AL-335 Drug: Odalasvir Drug: Simeprevir Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Percentage of Chronic HCV Infected Subjects who Achieve Sustained Virologic Response 12 weeks After the end of Treatment (EOT) (SVR12) [ Time Frame: 12 weeks after the EOT (Week 6 or 8) ]
    Subjects with SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) lower limit of quantification (LLOQ =15 IU/mL, detectable or undetectable) 12 weeks after EOT.


Secondary Outcome Measures:
  • Percentage of Subjects with Sustained Virologic Response at 4 (SVR4) and 24 (SVR24) Weeks After EOT [ Time Frame: 4 and 24 weeks after EOT ]
    Subjects with SVR4 and SVR24 is defined as if HCV RNA <lower limit of quantification (LLOQ) (detectable or undetectable) 4 and 24 weeks after EOT.

  • Percentage of Subjects With Viral Relapse During Follow-up up to 12 Weeks After EOT [ Time Frame: Up to Week 12 of follow up ]
    Subjects with viral relapse are defined as Subjects 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.

  • Percentage of Subjects With Late Viral Relapse During Follow-up Beyond Week 12 of Follow-up Up to Week 24 of Follow-up [ Time Frame: Beyond Week 12 of Follow-up Up to Week 24 of Follow-up ]
    Subjects with late viral relapse are defined as subjects who did achieve SVR12 but with confirmed HCV RNA >=LLOQ beyond Week 12 of Follow-up up to Week 24 of Follow-up.

  • Percentage of Subjects With On-treatment Failure [ Time Frame: Up to 6 or 8 weeks depending upon the Treatment received ]
    On-treatment failure is defined as subjects who do not achieve SVR12 with confirmed HCV RNA >/= LLOQ at the actual EOT. Includes subjects with a) viral breakthrough, defined as a confirmed increase of greater than (>) 1 log10 in HCV RNA from nadir, or confirmed HCV RNA >100 international unit (IU)/mL in subjects whose HCV RNA had previously been < LLOQ while on treatment; b) other with confirmed HCV RNA >/= LLOQ at the actual EOT (eg, completed study drug treatment, discontinued due to AEs, withdrawal of consent).

  • Percentage of Subjects With On-treatment Virologic Response [ Time Frame: Up to 6 or 8 weeks (on-treatment) ]
    On-treatment virologic response is defined as subjects with hepatitis C virus (HCV) RNA <LLOQ undetectable or <LLOQ (detectable or undetectable) at specified time points during treatment.

  • Time to Achieve Undetectable HCV RNA <LLOQ HCV RNA [ Time Frame: Up to 24 weeks of follow-up ]
  • Effect of Presence or Absence of Baseline NS5A, NS5B or NS3/4A Genes Polymorphisms on Treatment Outcome [ Time Frame: Baseline ]
    Effect of presence or absence of Baseline NS3/4A, NS5A and NS5B genes polymorphisms on following treatment outcome: SVR4, SVR12, SVR24, on-treatment failure, viral relapse, and emergence of resistance.

  • Changes from Baseline in Amino Acid Sequence in the HCV NS3/4A, NS5A and NS5B Genes in Subjects, who did not Achieve SVR [ Time Frame: Baseline up to 24 weeks of follow-up ]
  • Change from Baseline Over Time in 5-level EuroQol 5 Dimension (EQ-5D-5L) Visual Analog Scale (VAS) Score [ Time Frame: Baseline up to 24 weeks of follow-up ]
  • Change from Baseline Over Time in Fatigue Severity Scale (FSS) Total Score [ Time Frame: Baseline up to 24 weeks of follow-up ]
  • Percentage of Subjects with Clinically Significant Positive or Negative Change from Baseline in FSS Total and EQ-5D-5L VAS at Week 4, EOT (Week 6 or 8), Follow up Week 4, 12 and 24 [ Time Frame: Week 4, EOT, follow-up Week 4, 12 and 24 ]
  • Duration of Clinically Significant Positive or Negative Response from Baseline in FSS Total and EQ-5D-5L VAS at Week 4, EOT (Week 6 or 8), Follow up Week 4, 12 and 24 [ Time Frame: Week 4, EOT, follow-up Week 4, 12 and 24 ]
  • Predose (trough) Plasma Concentration (C0h) [ Time Frame: Baseline (Day 1) up to EOT ]
  • Area Under the Curve From Time Zero to 24 Hours Postdose (AUC 24) [ Time Frame: Baseline (Day 1) up to EOT ]
  • Number of Subjects with Adverse Events (AEs) [ Time Frame: Screening (Day 1) up to Week 38 (= Week 24 of Follow-up) ]

Enrollment: 365
Actual Study Start Date: November 2016
Study Completion Date: November 2017
Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 6 weeks.
Drug: AL-335
AL-335 800 mg (2*400) tablet will be administered once daily.
Drug: Odalasvir
Odalasvir 25 mg tablet will be administered once daily.
Drug: Simeprevir
Simeprevir 75 mg capsule will be administered once daily.
Experimental: Group B
AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 8 weeks.
Drug: AL-335
AL-335 800 mg (2*400) tablet will be administered once daily.
Drug: Odalasvir
Odalasvir 25 mg tablet will be administered once daily.
Drug: Simeprevir
Simeprevir 75 mg capsule will be administered once daily.

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02765490


Locations
Belgium
Antwerpen, Belgium
Bruxelles, Belgium
Edegem, Belgium
Gent, Belgium
Kortrijik, Belgium
Leuven, Belgium
Canada, British Columbia
Vancouver, British Columbia, Canada
Victoria, British Columbia, Canada
Canada, Ontario
Toronto, Ontario, Canada
Vaughan, Ontario, Canada
Canada, Quebec
Monteral, Quebec, Canada
Montreal, Quebec, Canada
Germany
Berlin, Germany
Essen, Germany
Frankfurt, Germany
Hamburg, Germany
Leipzig, Germany
Poland
Lodz, Poland
Lublin, Poland
Mysłowice, Poland
Warszawa, Poland
Wroclaw, Poland
Singapore
Singapore, Singapore
Spain
Barcelona, Spain
Madrid, Spain
Málaga, Spain
Seville, Spain
Valencia, Spain
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02765490     History of Changes
Other Study ID Numbers: CR108070
64294178HPC2001 ( Other Identifier: Janssen Research & Development, LLC )
2015-004200-38 ( EudraCT Number )
First Submitted: May 5, 2016
First Posted: May 6, 2016
Last Update Posted: December 5, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Hepatitis C, Chronic
AL-335
Odalasvir
Simeprevir
ODV
SMV
ACH-3102
ACH-0143102
TMC435

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Simeprevir
Antiviral Agents
Anti-Infective Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action