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Hepatitis C VirusPhase 2ACCORDION-1NCT02349048

Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection

A Phase 2 study testing Simeprevir 150 mg, Daclatasvir 60 mg and Sofosbuvir 400 mg in people with Hepatitis C Virus, run by Janssen Research & Development, LLC at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the efficacy of 6 or 8 weeks of treatment regimen containing simeprevir (SMV), daclatasvir (DCV) and sofosbuvir (SOF) in treatment-naive (not having received treatment with any approved or investigational drug) participants with chronic hepatitis (inflammation of the liver) C… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hepatitis C Virus
What is being tested?
Simeprevir 150 mg, Daclatasvir 60 mg and Sofosbuvir 400 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
8 sitesin 2 countries
Study dates
Jan 2015to May 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • HCV genotype 1 infection and HCV RNA plasma level greater than (>) 10,000 international units per milliliter (IU/mL), both determined at Screening
  • Participants of Arm A should have evidence of early stages of liver fibrosis, defined by a FibroSURE score less than or equal to (<=) 0.48 and aspartate aminotransferase to platelet ratio index (APRI) score <=1
  • Participants of Arm B should have evidence of cirrhosis, defined by a FibroSURE score >0.75 and APRI score >2, OR a previous (historical) biopsy documenting a METAVIR score F4. In addition, participants should have absence of esophageal varices or presence of small (grade 1) esophageal varices determined by upper gastrointestinal endoscopy, and absence of findings indicative of hepatocellular carcinoma in an ultrasonography
  • HCV treatment-naive, defined as not having received treatment with any approved or investigational drug for chronic HCV infection
  • Pegylated interferon (PegIFN) and ribavirin (RBV) eligible, defined as not having any contraindication to the use of PegIFN and RBV, in line with the prescribing information for each compound

Who cannot join

  • Main Study:
  • Co-infection with HCV of another genotype than genotype 1 and/or human immunodeficiency virus (HIV) type 1 or 2 (positive HIV-1 or HIV 2 antibody test at Screening)
  • Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, hepatitis B infection (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
  • Evidence of clinical hepatic decompensation or presence of grade 2/3 esophageal varices
  • Any of the protocol defined laboratory abnormalities
  • Sub-study:
Show all 9Show fewer
  • Presence of coagulopathy (hemophilia) or hemoglobinopathy (including sickle cell disease, thalassemia)
  • Use of any anti-coagulant (for example, warfarin, heparin) or anti-platelet medications within 1 week of the Screening visit
  • Any of the protocol defined laboratory abnormalities

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

United States7 sites

  • Study site

    Arlington, Texas

  • Study site

    Bakersfield, California

  • Study site

    Jacksonville, Florida

  • Study site

    Knoxville, Tennessee

  • Study site

    Lutherville, Maryland

  • Study site

    San Antonio, Texas

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

Canada1 site

  • Study site

    Toronto, Ontario

Other trials in Canada

About this study

Official title: A Phase 2, Randomized, Open-label Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of 6 or 8 Weeks of Treatment With Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Subjects With Chronic Hepatitis C Virus Genotype 1 Infection

The purpose of this study is to evaluate the efficacy of 6 or 8 weeks of treatment regimen containing simeprevir (SMV), daclatasvir (DCV) and sofosbuvir (SOF) in treatment-naive (not having received treatment with any approved or investigational drug) participants with chronic hepatitis (inflammation of the liver) C virus (HCV) genotype 1 infection with early stages of liver fibrosis or with cirrhosis.

Read the detailed description

This is an open-label (participants and researchers are aware about the treatment participants are receiving), and multicenter (when more than 1 hospital or medical school team work on a medical research) study. The study will consist of a Screening Phase (6 weeks); an Open-label Treatment Phase (6 weeks for Arm A and 8 weeks for Arm B); and a Post-treatment Follow-up Phase (until 24 weeks after end of study treatment). Using a staggered approach, all eligible participants will be assigned to 1 of the 2 arms, according to their level of fibrosis. Arm A (consists of chronic HCV genotype 1 infected participants with early stages of liver fibrosis): participants will receive a combination therapy of SMV 150 milligram (mg), DCV 60 mg and SOF 400 mg once daily for 6 weeks. Arm B (consists of chronic HCV genotype 1 infected participants with cirrhosis): participants will receive a combination therapy of SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks. A sub-study will be performed at a selected study site, where only participants who will be eligible to participate in both the main study and the sub-study will be enrolled. Intra-hepatic and plasma HCV ribonucleic acid (RNA) levels; intra-hepatic, peripheral innate and adaptive immune responses during the treatment, will be assessed in the sub-study. Participants' safety will be monitored throughout the study.

Being tested
Simeprevir 150 mg, Daclatasvir 60 mg, Sofosbuvir 400 mg
Keywords
Hepatitis C virus, Hepatitis C virus genotype 1, Chronic Hepatitis C Virus Genotype 1 Infection, Liver fibrosis, Cirrhosis, Simeprevir, Daclatasvir, Sofosbuvir
Medical subject headings
Hepatitis C, Liver Cirrhosis, Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Simeprevir 150 mgDrug

    Simeprevir 150 mg capsule orally once daily.

  • Daclatasvir 60 mgDrug

    Daclatasvir 60 mg tablet orally once daily.

  • Sofosbuvir 400 mgDrug

    Sofosbuvir 400 mg tablet orally once daily.

Study groups in NCT02349048
Study groupRoleWhat they receive
Arm AExperimentalChronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis, will receive Simeprevir (SMV) 150 milligram (mg), Daclatasvir (DCV) 60 mg and Sofosbuvir (SOF) 400 mg once daily for 6 weeks.
Receives: Drug: Simeprevir 150 mg; Drug: Daclatasvir 60 mg; Drug: Sofosbuvir 400 mg
Arm BExperimentalChronic HCV genotype 1 infected participants with cirrhosis, will receive SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks.
Receives: Drug: Simeprevir 150 mg; Drug: Daclatasvir 60 mg; Drug: Sofosbuvir 400 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12)

    Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the end of study drug treatment.

    Measured: 12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B)

Secondary outcomes (7)

  1. Percentage of Participants With On-treatment Virologic Response

    On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold.

    The following thresholds were considered at any time point: <LLOQ undetectable, <LLOQ detectable, and <LLOQ undetectable or detectable. The LLOQ value was 15 IU/mL. Very rapid virologic response (vRVR) is undetectable HCV RNA at Week 2 while on treatment and Rapid virologic response (RVR) is undetectable HCV RNA at Week 4 while on treatment.

    Measured: Day 2, Day 3, Week 1, 2, 3, 4, 6 (for Arm A) and 8 (for Arm B only)

  2. Percentage of Participants With Sustained Virologic Response at 4 Weeks (SVR4) and 24 Weeks (SVR24) After End of Study Drug Treatment

    Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was <LLOQ detectable or undetectable at 4 weeks and 24 weeks respectively after the end of study drug treatment. The LLOQ value was 15 IU/mL.

    Measured: 4 weeks after end of study drug treatment (week 10 for Arm A and 12 for Arm B); 24 weeks after end of study drug treatment (week 30 for Arm A and 32 for Arm B)

  3. Percentage of Participants With On-Treatment Failure

    Participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. Includes participants with: 1) viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA 2) confirmed detectable HCV RNA at the actual end of treatment (example, completed treatment, discontinued due to adverse events, withdrawal of consent) of >100 IU/mL in participants whose HCV RNA had previously been <LLOQ while on treatment.

    Measured: Baseline up to End of Treatment (Week 6 for Arm A and Week 8 for Arm B)

  4. Number of Participants With Viral Relapse

    Viral Relapse: Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during followup.

    Measured: From Week 6 to Week 18 (for Arm A) and From Week 8 to Week 20 (for Arm B)

  5. Number of Participants With Late Viral Relapse

    Late Viral Relapse: Participant who achieved SVR12 and the post treatment HCV RNA measurement fulfilled 1 the following conditions: a) at least 2 consecutive measurements not lesser than (<)15 IU/mL undetectable, of which at least the second measurement was >=15 IU/mL quantifiable or b) the last available measurement was >=15 IU/mL quantifiable.

    Measured: From Week 18 to Week 30 (for Arm A), From Week 20 to Week 32 (for Arm B)

  6. Number of Participants With HCV Nonstructural Protein 3/4A (NS3/4A), NS5A and NS5B Sequence in Participants Not Achieving SVR

    Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify preexisting sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR.

    Measured: Up to Week 30 for Arm A and up to Week 32 for Arm B

  7. Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR

    The Q80K polymorphism, associated with low level SMV in vitro resistance. Percentage of participants who achieved SVR with or without an NS3 Q80K polymorphism at baseline were reported.

    Measured: up to Week 30 for Arm A and Week 32 for Arm B

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2015 (estimated)
  2. Study startJan 2015
  3. Primary completionFeb 2016
  4. Study completionMay 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02349048
Sponsor's protocol ID
CR105963
Other IDs
TMC435HPC2013
Acronym
ACCORDION-1
Status last verified
Jan 2017
First submitted
22 Jan 2015
Last updated
1 Mar 2017
Data monitoring committee
Yes

Publications

  • Sulkowski MS, Feld JJ, Lawitz E, Felizarta F, Corregidor AM, Khalid O, Ghalib R, Smith WB, Van Eygen V, Luo D, Vijgen L, Gamil M, Kakuda TN, Ouwerkerk-Mahadevan S, Van Remoortere P, Beumont M. Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection. J Viral Hepat. 2018 Jun;25(6):631-639. doi: 10.1111/jvh.12853. Epub 2018 Feb 6.

    PubMed 29274193

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Simeprevir 150 mg, Daclatasvir 60 mg and Sofosbuvir 400 mg in people with Hepatitis C Virus, run by Janssen Research & Development, LLC at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12) (time frame: 12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02349048, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2017.

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