Effectiveness Of Daclatasvir-Based Regimens In Patients With Chronic Hepatitis C Infection In Europe: Experience From Named Patient Program And From Early Post-Marketing Authorization Period

Using European data from patients included in the Named Patient Program (NPP) and from the early post-marketing authorization period, the present study aims to describe patient characteristics and to describe the effectiveness of Daclatasvir (DCV)-based regimens in Europe. This will be a retrospective cohort study of patients who received treatment with a DCV-based regimen in the following context:

• Patients enrolled within the European NPP in one of the following countries Austria, Denmark, Italy, Sweden, Spain, Switzerland, United Kingdom; or
• In those countries where DCV is commercially available (ie, Sweden, Germany, United Kingdom), patients who received DCV during the early post-marketing authorization period

The results of this study will contribute to a better understanding of effectiveness of DCV-based regimens in a population that differs from population in the clinical trials, and therefore will provide additional valuable information to inform clinical practice.

This study intends to estimate primarily the effectiveness of DCV-based regimens as measured by the sustained virologic response at post treatment follow-up visit week 12 (SVR12). As well as estimate the effectiveness of DCV-based regimens as measured by SVR12 after the end of Hepatitis C virus (HCV).

This study intends also to describe as secondary objectives the characteristics (ie, demographic and clinical characteristics and treatment patterns of patients starting a new DCV-based regimens) of patients receiving DCV as well as the effectiveness of DCV-based regimens as measured by:

• On-treatment virological response at post treatment follow-up visit Week 4; and
• Virological response at the end of treatment (EOT); and
• The sustained viral response at post treatment follow-up visit Week 4 (SVR4) and post treatment follow-up visit Week 24 (SVR24); and
• The occurrence of virological failure (on-treatment and relapse).

An exploratory objective will be to assess the concordance between SVR4 and SVR12 among the overall population treated with DCV.

Study Overview

• Status: Completed
• Conditions: Hepatitis C

• Study Type: Observational
• Enrollment (Actual): 249

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population was selected from European HCV registries or databases in specific health-care facilities from Austria, Denmark, Italy, Sweden, Spain, Switzerland, and United Kingdom (UK)

Description

Inclusion Criteria:

• Patients participating in the DCV NPP from 7 European countries (Austria, Denmark, Italy, Sweden, Spain, Switzerland, and UK). The following patients were eligible to participate in the NPP

  • The patient have a serious or life-threatening condition that is impacting life expectancy within 12 months.
  • There are no comparable or satisfactory alternative treatments options exist for the patient, and/or currently available treatment options have been exhausted.
  • The patient was ineligible to participate in a clinical trial, or there was no ongoing clinical trial in the patient´s country of residence to treat his/her HCV-infection.
• In countries where DCV is commercially available at time of study initiation(Sweden, UK, and Germany), patients treated with DCV during the early post-marketing authorization period.
• Patients initiating any DCV-based regimen during the inclusion periods.
• Recorded in one of the HCV data sources used for the study.

Exclusion Criteria:

• Patients included in the DCV Compassionate use program (CUP) (AI444-237 Protocol) open in 6 European countries (Germany, Austria, Sweden, Netherlands, Norway and UK) after Committee for Medicinal Products for Human Use (CHMP) opinion for the DCV CUP in Europe will be excluded since these patients will be analyzed as part of separate datasets.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Patients treated with DCV (NPP)+Sofosbuvir +/- Ribavirin (RBV)
Patients treated with DCV (NPP) + Simeprevir +/- RBV
Patients treated with DCV(post-marketing) + Sofosbuvir +/- RBV
Patients treated with DCV(post-marketing) + Simeprevir +/- RBV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SVR12	Effectiveness of DCV-based regimens as measured by the SVR12, overall and in specific patient sub-populations	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SVR4	Effectiveness of DCV-based regimens as measured by SVR4	Up to 36 months
SVR24	Effectiveness of DCV-based regimens as measured by SVR24	Up to 36 months
On-treatment Virological response at week 4 assessed by measuring viral load		Up to 36 months
Virological response at the end of treatment (EOT) assessed by measuring viral load		Up to 36 months
The occurrence of virological failure (on-treatment and relapse) assessed by measuring viral load	Virological failure is defined as virologic breakthrough, other on-treatment failure or relapse, where: Virologic breakthrough is defined as confirmed ≥ 1 log10 IU/mL HCV RNA on treatment increase from nadir, or confirmed increase in HCV RNA ≥ LLOQ if HCV RNA previously declined to < LLOQ (TD/TND). (LLOQ: Lower limit of quantification); Relapse is defined as HCV RNA < LLOQ (TND) at End of Treatment followed by confirmed detectable HCV RNA ≥ LLOQ in any follow-up visit window.; On-treatment failure is defined as HCV RNA ≥ LLOQ at any time point not meeting the definition of virologic breakthrough or relapse.	Up to 36 months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Basel Institute of Clinical Epidemiology (BICE)

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: August 11, 2015
• First Submitted That Met QC Criteria: August 21, 2015
• First Posted (Estimate): August 24, 2015

Study Record Updates

• Last Update Posted (Estimate): May 9, 2016
• Last Update Submitted That Met QC Criteria: May 6, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: AI444-319