AzTrials
AzTrials

Hepatitis C VirusPhase 2NCT01628692

Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus

A Phase 2 study testing Daclatasvir, Simeprevir and Ribavirin in people with Hepatitis C Virus, run by Bristol-Myers Squibb at 26 sites in 6 countries.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to assess the safety and efficacy of daclatasvir and simeprevir with and without ribavirin for genotype 1 chronic hepatitis C virus infection in patients who are treatment-naive or null responders to previous pegylated interferon/ribavirin therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatitis C Virus
What is being tested?
Daclatasvir, Simeprevir and Ribavirin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
230 participants
Where
26 sitesin 6 countries
Study dates
Jul 2012to Nov 2013
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Hepatitis C virus (HCV) genotype 1a or 1b
  • Males and females, ≥18 years of age
  • HCV RNA ≥10,000 IU/mL
  • Participants with compensated cirrhosis are permitted
  • Advanced fibrosis (F3/F4) is capped at approximately 35% of the total treated population with a minimum of 20% F4 patients
  • If no cirrhosis, a liver biopsy within 3 years prior to enrollment
  • If cirrhosis is present, any prior liver biopsy

Who cannot join

  • Liver or any other transplant (other than cornea and hair)
  • Evidence of a medical condition contributing to chronic liver disease other than HCV infection
  • Current or known history of cancer, (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
  • Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
  • Patients infected with HIV or hepatitis B virus
  • Gastrointestinal disease impacting absorption of study drug
Show all 21Show fewer
  • Uncontrolled diabetes or hypertension
  • Prior exposure to an HCV direct-acting agent
  • Any criteria that would exclude the patient from receiving ribavirin
  • Absolute neutrophil count <1.5*1,000,000,000 cells/L (<1.2*1,000,000,000 cells/L for Black/African Americans)
  • Platelets <90*1,000,000,000 cells/L
  • Hemoglobin <12 g/dL for females, <13 g/dL for males
  • Alanine aminotransferase ≥5*upper limit of normal
  • In patients without cirrhosis, total bilirubin ≥2 mg/dL unless patient has a documented history of Gilbert's disease
  • In patients with cirrhosis, total bilirubin o ≥1.5 mg/dL
  • International normalized ratio ≥1.7
  • QTcF or QTcB >500 mSec
  • Creatinine clearance ≤50 mL/min
  • Alpha fetoprotein (AFP) >100 ng/mL OR
  • AFP ≥50 ng/mL and ≤100 ng/mL requiring liver ultrasound
  • Albumin <3.5 g/dL

Trial locations and contacts

26 sites in 6 countries.

26 sites in 6 countries

United States7 sites

  • Texas Clinical Research Institute, Llc

    Arlington, Texas, 76012

  • Metropolitan Research

    Fairfax, Virginia, 22031

  • Indiana University

    Indianapolis, Indiana, 46202

  • Johns Hopkins University

    Lutherville, Maryland, 21093

  • Nashville Medical Research Institute

    Nashville, Tennessee, 37205

  • San Francisco General Hospital

    San Francisco, California, 94110

  • Kaiser Permanente Med Ctr

    San Francisco, California, 94118

Other trials in United States

France7 sites

  • Local Institution

    Créteil, 94010

  • Local Institution

    Limoges, 87042

  • Local Institution

    Marseille, 13285

  • Local Institution

    Paris, 75651

  • Local Institution

    Paris, 75679

  • Local Institution

    Pessac, 33600

  • Local Institution

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Germany4 sites

  • Local Institution

    Berlin, 10969

  • Local Institution

    Cologne, 50937

  • Local Institution

    Frankfurt, 60590

  • Local Institution

    Hamburg, 20099

Other trials in Germany

Hungary3 sites

  • Local Institution

    Budapest, 1097

  • Local Institution

    Budapest, 1126

  • Local Institution

    Gyula, 5700

Other trials in Hungary

Spain3 sites

  • Local Institution

    Barcelona, 08035

  • Local Institution

    Madrid, 28046

  • Local Institution

    Valencia, 46010

Other trials in Spain

Argentina2 sites

  • Local Institution

    Buenos Aires, Buenos Aires, 1119

  • Local Institution

    Buenos Aires, Buenos Aires, C1181ACH

Other trials in Argentina

About this study

Official title: A Phase 2, Open-Label Study of Daclatasvir (BMS-790052) and TMC435 in Combination With or Without Ribavirin (RBV) For Treatment-Naive Subjects or Null Responders to Prior Peginterferon Alfa (PegIFN)/RBV Therapy With Genotype 1 Chronic Hepatitis C

The purpose of this study is to assess the safety and efficacy of daclatasvir and simeprevir with and without ribavirin for genotype 1 chronic hepatitis C virus infection in patients who are treatment-naive or null responders to previous pegylated interferon/ribavirin therapy.

Being tested
Daclatasvir, Simeprevir, Ribavirin
Medical subject headings
Hepatitis C

What participants receive

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

  • DaclatasvirDrug

    Also called BMS-790052

    Tablets, oral, 30 mg, once daily

  • SimeprevirDrug

    Also called TMC435

    Capsule, oral, 150 mg, once daily

  • RibavirinDrug

    Tablets, oral, 500-600 mg, twice daily

Study groups in NCT01628692
Study groupRoleWhat they receive
Cohort 1: (Genotype 1b) Daclatasvir + SimeprevirExperimentalParticipants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal for 12 weeks
Receives: Drug: Daclatasvir; Drug: Simeprevir
Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + RibavirinExperimentalParticipants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day) for 12 weeks.
Receives: Drug: Daclatasvir; Drug: Simeprevir
Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + RibavirinExperimentalParticipants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day) for 12 weeks.
Receives: Drug: Daclatasvir; Drug: Simeprevir; Drug: Ribavirin
Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + RibavirinExperimentalParticipants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day.
Receives: Drug: Daclatasvir; Drug: Simeprevir; Drug: Ribavirin

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 Rate at Post-treatment Week 12 (SVR12)

    SVR12 rate was defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

    Measured: Post Treatment Week 12 (Follow-up period)

Secondary outcomes (6)

  1. Percentage of Participants With Rapid Virologic Response (RVR) at Week 4

    RVR was defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target not detected at Week 4. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

    Measured: Week 4

  2. Percentage of Participants With Complete Early Virologic Response (cEVR)

    cEVR was defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target not detected at Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

    Measured: Week 12

  3. Percentage of Participants With Extended Rapid Virologic Response (eRVR)

    eRVR were defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target not detected at both Week 4 and Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

    Measured: Week 4 and Week 12

  4. Percentage of Participants With End of Treatment Response (EOTR)

    EOTR were defined as hepatitis C virus (HCV) RNA levels <lower limit of quantitation, target not detected at end of treatment. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

    Measured: End of treatment (Week 24)

  5. Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories

    Participants were categorized into 3 genotypes based on single nucleotide polymorphisms in the IL28B gene. SVR12 was defined as hepatitis C virus (HCV) RNA levels below lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

    Measured: Baseline, post-treatment Week 12 (Follow-up period)

  6. Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died

    AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

    Measured: From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24)

Timeline

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

  1. First posted27 Jun 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionAug 2013
  4. Study completionNov 2013

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
230 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01628692
Sponsor's protocol ID
AI444-062
Other IDs
2012-000070-28
Status last verified
Jan 2017
First submitted
25 Jun 2012
Last updated
23 Feb 2017
Data monitoring committee
Yes

Publications

  • Zeuzem S, Hezode C, Bronowicki JP, Loustaud-Ratti V, Gea F, Buti M, Olveira A, Banyai T, Al-Assi MT, Petersen J, Thabut D, Gadano A, Pruitt R, Makara M, Bourliere M, Pol S, Beumont-Mauviel M, Ouwerkerk-Mahadevan S, Picchio G, Bifano M, McPhee F, Boparai N, Cheung K, Hughes EA, Noviello S; LEAGUE-1 Study Team. Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection. J Hepatol. 2016 Feb;64(2):292-300. doi: 10.1016/j.jhep.2015.09.024. Epub 2015 Oct 8.

    PubMed 26453968

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daclatasvir, Simeprevir and Ribavirin in people with Hepatitis C Virus, run by Bristol-Myers Squibb at 26 sites in 6 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 7 inclusion and 21 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 23 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, France, Germany, Hungary, Spain and 1 more country. 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 30 Nov 2015). 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 Rate at Post-treatment Week 12 (SVR12) (time frame: Post Treatment Week 12 (Follow-up period)). 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 NCT01628692, 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 23 Feb 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in