An Efficacy, Safety, Tolerability and Pharmacokinetics Study of 12 Weeks Treatment With Simeprevir and Daclatasvir in Participants With Chronic Hepatitis C Virus Genotype 1b or 4 Infection and Either Severe Renal Impairment or End-stage Renal Disease on Hemodialysis.

End-stage Renal Disease Clinical Trial

Official title:

A Phase 2, Open-label, Single-arm Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of 12 Weeks Treatment With Simeprevir and Daclatasvir in Subjects With Chronic Hepatitis C Virus Genotype 1b or 4 Infection and Either Severe Renal Impairment or End-stage Renal Disease on Hemodialysis.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02397395
• Other study ID #: CR106396
• Secondary ID: TMC435HPC2018201
• Status: Withdrawn
• Phase: Phase 2
• First received: March 19, 2015
• Last updated: July 15, 2015
• Start date: May 2015
• Est. completion date: May 2016

Study information

• Verified date: July 2015
• Source: Janssen R&D Ireland
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the percentage of participants with sustained virologic response 12 weeks after the actual end of study treatment (SVR12)

Description:

This is a Phase 2, open-label (identity of study drug will be known to volunteer and study staff), single-arm, multicenter (when more than one hospital work on a medical research study) study to evaluate the efficacy, safety, tolerability and pharmacokinetics of 12 weeks treatment with Simeprevir (SMV) and Daclatasvir (DCV) in participants with chronic Hepatitis C Virus (HCV) genotype 1b or 4 infection and either severe renal impairment or End-stage Renal Disease on hemodialysis. The study consists of a Screening Phase of 4 weeks, an Open-label Treatment Phase of 12 weeks, and a post-Treatment Follow-up Phase of 24 weeks. The total study duration for each participant will be approximately 40 weeks. All participants will receive a treatment regimen consisting of SMV 150 mg and DCV 60 mg co-administered once daily for a total treatment duration of 12 weeks. Participants who experience inadequate virologic response at Week 8 (defined as confirmed HCV RNA greater than or equal to [>=] lower limit of quantification [LLOQ]) or viral breakthrough at any on-treatment visit (defined as confirmed increase in HCV RNA of >1 log base 10 from nadir, or confirmed HCV RNA >100 International unit per milliliter [IU/mL] in participants whose HCV RNA had previously been

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Man or woman, between 18 and 70 years of age, inclusive, at screening

• Hepatitis C Virus (HCV genotype): HCV genotype 1b or 4 (determined at screening)

• Plasma HCV RNA: Greater than (>) 10,000 international unit per milliliter (IU/mL) (determined at screening)

• HCV disease status: FibroScan less than (<) 14.5 kilopascal (kPa), performed within 3 months prior to screening, or between screening and baseline (Day 1), and no history or signs or symptoms of decompensated liver disease. In participants with FibroScan >12.5 kPa, absence of findings suspicious for hepatocellular carcinoma documented by an abdominal ultrasound, performed within 3 months prior to screening, or between screening and baseline (Day 1)

• HCV treatment history: HCV treatment-naive participants, defined as never having received HCV treatment with any approved or investigational drug (including vaccines); OR HCV treatment-experienced, defined as having received previous HCV treatment with any (pegylated) interferon ([Peg]IFN)-based drug regimen (with or without ribavirin [RBV] and not including a direct-acting antiviral agent [DAA]). Last dose in this previous HCV treatment course should have occurred at least 2 months prior to screening

Exclusion Criteria:

• Infection/co-infection: HCV genotype other than 1b or 4, Human immunodeficiency virus type 1 or 2

• Liver disease of non-HCV etiology: Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A, hepatitis B (hepatitis B surface antigen positive), drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the investigator

• Hepatic decompensation: History or evidence of clinical hepatic decompensation (presence of ascites, bleeding varices or hepatic encephalopathy)

• Organ transplantation/renal replacement therapy: Prior organ transplant (other than cornea, hair transplant or skin graft), except for history of kidney transplant with subsequent renal failure requiring hemodialysis and for which use of immunosuppressants has been discontinued; Considered for kidney transplant or imminent renal replacement therapy (including intermittent hemodialysis; continuous hemofiltration and hemodialysis; and peritoneal dialysis) for participants with severe renal impairment within a time frame that overlaps with study participation

• Key protocol defined laboratory abnormalities

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• End-stage Renal Disease
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Simeprevir (SMV) 150 mg
Simeprevir (SMV) 150 milligram (mg) capsule orally, once daily for a duration of 12 weeks.
• Daclatasvir (DCV) 60 mg
Daclatasvir (DCV) 60 mg tablet, orally, once daily for a duration of 12 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen R&D Ireland

Countries where clinical trial is conducted

France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response at Week 12 After End of Treatment (SVR12)	SVR12 is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) lower limit of quantification (LLOQ); , detectable or undetectable at 12 weeks after EOT.	12 weeks after end of treatment (EOT) (Week 12 of follow-up phase)	No
Secondary	Percentage of Participants With On-treatment Response	HCV RNA results satisfying a specified threshold. The following thresholds will be considered at any time point:	Baseline up to EOT (Week 12)	No
Secondary	Percentage of Participants With Sustained Virologic Response at Week 4 After End of Treatment (SVR4)	SVR4 is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) lower limit of quantification (LLOQ) , detectable or undetectable at 4 weeks after EOT.	4 weeks after EOT (Week 4 of follow-up phase)	No
Secondary	Percentage of Participants With Sustained Virologic Response at Week 24 After End of Treatment (SVR24)	SVR24 is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) lower limit of quantification (LLOQ) , detectable or undetectable at 24 weeks after EOT.	24 weeks after EOT (Week 24 of follow-up phase)	No
Secondary	Percentage of Participants With on-treatment Failure	Participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study treatment.	Baseline up to EOT (Week 12), 12 weeks after EOT (Week 12 of follow-up phase)	No
Secondary	Percentage of Participants With Viral Relapse	Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study treatment and confirmed HCV RNA >=LLOQ during 24-week follow-up.	EOT (Week 12) until end of follow-up phase (Week 24 of follow-up phase)	No
Secondary	Change From Baseline in Hepatitis C Virus (HCV) Nonstructural Protein 3/4A (NS3/4A) and Nonstructural Protein 5A (NS5A) Sequence in Participants not Achieving SVR		Baseline until end of follow-up phase (Week 24 of follow-up phase)	No
Secondary	Change From Baseline in HCV Symptom and Impact Questionnaire version 4 (HCV-SIQv4) Overall Body Symptom score	The HCV-SIQv4 is a self-administered questionnaire containing 33 items (ranging from 0=Not at All to 4=Extremely): 29 questions developed to assess the severity or frequency of symptoms associated with HCV or its treatment, 3 questions regarding the impact of symptoms on work/school attendance, and 1 question regarding the impact of symptoms on daily activities. Higher HCV-SIQv4 scores indicate worse symptom severity, more time missed from work or school, and more impairment in daily activities, respectively.	Baseline until end of follow-up phase (Week 24 of follow-up phase)	No