Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus
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ClinicalTrials.gov Identifier: NCT01628692 |
Recruitment Status :
Completed
First Posted : June 27, 2012
Results First Posted : November 30, 2015
Last Update Posted : February 23, 2017
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Condition or disease | Intervention/treatment | Phase |
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Hepatitis C Virus | Drug: Daclatasvir Drug: Simeprevir Drug: Ribavirin | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 230 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Study Start Date : | July 2012 |
Actual Primary Completion Date : | August 2013 |
Actual Study Completion Date : | November 2013 |

Arm | Intervention/treatment |
---|---|
Experimental: Cohort 1: (Genotype 1b) Daclatasvir + Simeprevir
Participants 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
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Drug: Daclatasvir
Tablets, oral, 30 mg, once daily
Other Name: BMS-790052 Drug: Simeprevir Capsule, oral, 150 mg, once daily
Other Name: TMC435 |
Experimental: Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + Ribavirin
Participants 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.
|
Drug: Daclatasvir
Tablets, oral, 30 mg, once daily
Other Name: BMS-790052 Drug: Simeprevir Capsule, oral, 150 mg, once daily
Other Name: TMC435 |
Experimental: Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants 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.
|
Drug: Daclatasvir
Tablets, oral, 30 mg, once daily
Other Name: BMS-790052 Drug: Simeprevir Capsule, oral, 150 mg, once daily
Other Name: TMC435 Drug: Ribavirin Tablets, oral, 500-600 mg, twice daily |
Experimental: Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants 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.
|
Drug: Daclatasvir
Tablets, oral, 30 mg, once daily
Other Name: BMS-790052 Drug: Simeprevir Capsule, oral, 150 mg, once daily
Other Name: TMC435 Drug: Ribavirin Tablets, oral, 500-600 mg, twice daily |
- Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12) [ Time Frame: Post Treatment Week 12 (Follow-up period) ]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.
- Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 [ Time Frame: 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.
- Percentage of Participants With Complete Early Virologic Response (cEVR) [ Time Frame: Week 12 ]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.
- Percentage of Participants With Extended Rapid Virologic Response (eRVR) [ Time Frame: Week 4 and Week 12 ]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.
- Percentage of Participants With End of Treatment Response (EOTR) [ Time Frame: End of treatment (Week 24) ]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.
- Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories [ Time Frame: Baseline, post-treatment Week 12 (Follow-up period) ]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.
- Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died [ Time Frame: From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24) ]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.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Hepatitis C virus (HCV) genotype 1a or 1b
- Males and females, ≥18 years of age
- HCV RNA ≥10,000 IU/mL
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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
Key Exclusion Criteria:
- 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
- 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

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): NCT01628692
United States, California | |
San Francisco General Hospital | |
San Francisco, California, United States, 94110 | |
Kaiser Permanente Med Ctr | |
San Francisco, California, United States, 94118 | |
United States, Indiana | |
Indiana University | |
Indianapolis, Indiana, United States, 46202 | |
United States, Maryland | |
Johns Hopkins University | |
Lutherville, Maryland, United States, 21093 | |
United States, Tennessee | |
Nashville Medical Research Institute | |
Nashville, Tennessee, United States, 37205 | |
United States, Texas | |
Texas Clinical Research Institute, Llc | |
Arlington, Texas, United States, 76012 | |
United States, Virginia | |
Metropolitan Research | |
Fairfax, Virginia, United States, 22031 | |
Argentina | |
Local Institution | |
Buenos Aires, Argentina, 1119 | |
Local Institution | |
Buenos Aires, Argentina, C1181ACH | |
France | |
Local Institution | |
Creteil Cedex, France, 94010 | |
Local Institution | |
Limoges, France, 87042 | |
Local Institution | |
Marseille Cedex 08, France, 13285 | |
Local Institution | |
Paris Cedex 13, France, 75651 | |
Local Institution | |
Paris Cedex 14, France, 75679 | |
Local Institution | |
Pessac, France, 33600 | |
Local Institution | |
Vandoeuvre Les Nancy, France, 54511 | |
Germany | |
Local Institution | |
Berlin, Germany, 10969 | |
Local Institution | |
Frankfurt, Germany, 60590 | |
Local Institution | |
Hamburg, Germany, 20099 | |
Local Institution | |
Koeln, Germany, 50937 | |
Hungary | |
Local Institution | |
Budapest, Hungary, 1097 | |
Local Institution | |
Budapest, Hungary, 1126 | |
Local Institution | |
Gyula, Hungary, 5700 | |
Spain | |
Local Institution | |
Barcelona, Spain, 08035 | |
Local Institution | |
Madrid, Spain, 28046 | |
Local Institution | |
Valencia, Spain, 46010 |
Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Bristol-Myers Squibb |
ClinicalTrials.gov Identifier: | NCT01628692 |
Other Study ID Numbers: |
AI444-062 2012-000070-28 ( EudraCT Number ) |
First Posted: | June 27, 2012 Key Record Dates |
Results First Posted: | November 30, 2015 |
Last Update Posted: | February 23, 2017 |
Last Verified: | January 2017 |
Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections |
Flaviviridae Infections Hepatitis, Chronic Ribavirin Simeprevir Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Protease Inhibitors Enzyme Inhibitors |