Two phase III trials evaluating once-daily Simeprevir and Sofosbuvir in hepatitis C infected patients have been initiated

Stockholm, Sweden — Medivir AB (OMX: MVIR) today announces that two phase III trials are recruiting patients to examine the efficacy and safety of the NS3/4A protease inhibitor simeprevir in combination with the nucleotide inhibitor sofosbuvir for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection in treatment-naïve and treatment-experienced patients with and without cirrhosis.

“Positive safety and efficacy results have previously been demonstrated in genotype 1 HCV infected patients with the interferon- and ribavirin free combination of simeprevir and sofosbuvir in the phase II COSMOS study. The OPTIMIST trials aim to further consolidate these data and to explore a shorter treatment duration of eight weeks to potentially further simplify this promising treatment option,” says Charlotte Edenius, EVP Development, Medivir AB

Study design
OPTIMIST-1
The first trial, called OPTIMIST-1 or TMC435HPC3017, is a phase III, open-label, randomized study investigating the efficacy and safety of simeprevir 150 mg in combination with sofosbuvir 400 mg.
The combination will be administered once daily for 8 or 12 weeks in chronic HCV genotype 1 infected patients without cirrhosis who are HCV treatment naïve or treatment experienced. This study will enroll approximately 300 patients in the U.S. and Canada.

OPTIMIST-2
The second trial, called OPTIMIST-2 or TMC435HPC3018, is a phase III, open-label, single-arm study investigating the efficacy and safety of simeprevir 150 mg in combination with sofosbuvir 400 mg.
The combination will be administered once daily for 12 weeks in HCV genotype 1 infected patients with cirrhosis who are HCV treatment naïve or treatment experienced. This study will enroll approximately 100 patients in the U.S. and Canada.

Ribavirin will not be administered in the OPTIMIST trials. The primary efficacy endpoint in each study is the proportion of patients achieving sustained virologic response 12 weeks after the end of treatment (SVR12).

For additional information, including inclusion and exclusion criteria for these trials, please visit www.clinicaltrials.gov

COSMOS study
The combination of simeprevir and sofosbuvir was previously evaluated in the phase II COSMOS trial.
The final cohort 1 study results (SVR12) in patients without fibrosis or cirrhosis (METAVIR score of F0-2) and the interim cohort 2 study results (SVR4) in patients with fibrosis or cirrhosis (METAVIR score of F3-4) from the COSMOS study were presented at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting 2013 in Washington, D.C.

Final cohort 2 results (SVR12) have been accepted for presentation at the European Association for the Study of the Liver (EASL) International Liver Congress 2014 on April 12.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 13.00 CET on 2 April 2014.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated for the treatment chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 and 4 infected patients with compensated liver disease, including cirrhosis.

Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB will retain marketing rights for simeprevir in these countries under the marketing authorization held by Janssen-Cilag International NV. The treatment was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in November 2013 in Canada and the U.S. and in March 2014 in Russia. The Committee for Medicinal Products for Human Use (CHMP) recently recommended Marketing Authorisation in the European Union for the use of Simeprevir in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adult patients. An approval is expected during Q2-2014.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

Source

Paid Hepatitis C Clinical Trial Now Enrolling at Avail Clinical Research near Orlando, Florida; Accepting M/F Patients with Chronic Hepatitis C Age 18-65

Avail is conducting a randomized study to evaluate the safety and efficacy of a new hepatitis drug in combinations with simeprevir and/or ritonavir with or without Ribavirin for 12 weeks in participants with chronic hepatitis C infection.

DeLand, FL (PRWEB) January 22, 2014

*To see if you qualify for this Hepatitis C Clinical Trial in Florida, visit Avail Clinical Research on the web (http://www.availclinical.com) or contact us directly at (386) 785-2404. There is no cost to participate, no insurance is required, and you may receive compensation for time and travel.

STUDY DESIGN

The study will be conducted in three parts. Part A will utilize a randomized group design in treatment-naive, GT!b and 4 HCV-infected subjects. Sixty subjects will be enrolled and randomized to groups of equal size. GT!b and GT4 HCV-infected subjects will be stratified by genotype across the treatment arms. Each group will receive the study drugs for up to 12 weeks followed by a 24-week follow-up to determine sustained virologic response (SVR).

Part B will be a randomized, open-label, parallel-group design in treatment-naive, GT!b, 4 and 6 HCV-infected subjects. Enrollment into Part B will commence following enrollment completion of Part A. GT!b and GT4 HCV-infected subjects will be stratified by genotype between treatment arms in Cohorts I b and 2b. Per Amendment 5, enrollment into the I00 mg RBV-free arm was capped at the number of subjects who had already been dosed into that cohort, and RBV was immediately added to their treatment regimen.

Part C will be an open-label, randomized, parallel group design in treatment-naive or IFN/RBV-treatment relapsed, GT!a and GT!b HCV-infected subjects. An independent DSMB will review the available PK, safety, and antiviral activity data after all subjects have completed 4 weeks of treatment.

BACKGROUND & RATIONALE

Hepatitis C virus (HCV) infection is a global public health problem. The global prevalence of chronic hepatitis C infection is estimated to be approximately 150 million HCV-infected persons worldwide. An estimated 60-70% of chronically infected people develop chronic liver disease; 5-20% develop cirrhosis and 1-5% die from cirrhosis or liver cancer. In 25% of liver cancer patients, the underlying cause is hepatitis C.

This new hepatitis C drug is being developed as a novel, HCV nonstructural protein S A (NSSA) inhibitor agent for the therapy of chronic hepatitis C. This drug acts as a potent inhibitor of HCV replication, inhibiting HCV of Genotypes (GT) l a, l b, 2a, 3a, 4a and Sa in vitro with half maximal effective concentration (ECso) values ranging from 2 to 24 pM, suggesting that it has pan-genotypic activity.

PRIMARY OBJECTIVES

The primary objectives of this study are to evaluate the:

• Safety and tolerability of 2- and 3-drug combinations of the new hepatitis C drug, simeprevir, ritonavir, with or without RBV for up to 12 weeks.
• Efficacy of a 2-DAA combination treatment (new hepatitis drug and simeprevir) with RBV for up to 12 weeks.
• Efficacy of a 3-DAA combination treatment (new hepatitis drug, simeprevir, ritonavir) with or without RBV for up to 12 weeks.

INCLUSION CRITERIA

• 18 to 65 years of age, inclusive.
• Female subjects of both childbearing potential and non-childbearing potential may be included, unless the local regulatory authority requires that only females of non­ childbearing potential be included. Non-childbearing potential is defined as one of the following:
• Postmenopausal, defined as amenorrheic for at least 2 years and serum follicle stimulating hormone (FSH) level consistent with postmenopausal status at Screening, OR
• A documented hysterectomy, bilateral oophorectomy or bilateral tubal ligation at least 6 months prior to study initiation.
• All female subjects must have a negative serum beta-human chorionic gonadotropin (P-HCG) at Screening and a negative urine pregnancy test prior to the first dose of study medication on Day J.
• Women of childbearing potential and men must have agreed to use an acceptable double method of birth control (one of which must be a barrier method) from Screening through at least 6 months after the last dose of study drugs.
• The co-administration of RTV with ethinyl estradiol (oral or patch) may result in decreased contraceptive effectiveness. Women in Part C who are receiving estrogen­ based hormonal contraceptives, must agree to use alternate contraceptive measures for the estrogen-based contraceptive. They must still fulfill the requirement to use an acceptable double method of birth control (one of which must be a barrier method).
• Male subjects must have agreed not to donate sperm from the first dose through at least 6 months after the last dose of study drugs.
• QTcF interval: S 450 ms at Screening and prior to dosing on Day 1.
• Documented clinical history compatible with chronic hepatitis C, including any one of the following:
• Anti- HCV antibody positive at least 6 months prior to Screening or dosing, OR
• HCV RNA present in plasma by a sensitive and specific assay at least 6 months prior to Screening or dosing, OR
• HCV genotype at least 6 months prior to Screening or dosing, OR
• Histologic evidence of chronic hepatitis C infection.
• Plasma HCV RNA positive at Screening with minimal viral load according to genotype:
• GTI a (Q80K negative), I b and 6 HCV RNA 2::5 log10 IU/mL
• GT4 HCV RNA 2:: 4 log10 IU/mL
• Documented absence of cirrhosis within 36 months of Screening or dosing (histology or non-invasive equivalent, according to local standard of care).
• Subject is, in the opinion of the investigator, willing and able to comply with the protocol and all other study requirements.
• Subject has provided written informed consent to participate in the study.
• Avail Clinical Research conducts a variety of Clinical Trials in Florida. For more information about participating in a Hepatitis C Clinical Study, please visit our website or contact us directly at (386) 785-2404.

Source

Clinical Trial: Phase III HIV/HCV Co-Infection Daclatasvir (DCV) + Sofosbuvir (SOF) (ALLY 2)

This study is not yet open for participant recruitment.

Verified January 2014 by Bristol-Myers Squibb

Sponsor: Bristol-Myers Squibb

Information provided by (Responsible Party): Bristol-Myers Squibb

ClinicalTrials.gov Identifier: NCT02032888
First received: January 9, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted

Purpose

To study the combination of Daclatasvir and Sofosbuvir for the treatment of HCV/ HIV Coinfection

Condition	Intervention	Phase
Hepatitis C	Drug: Daclatasvir Drug: Sofosbuvir	Phase 3

Study Type: Interventional

Study Design:
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Official Title:
A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C (Genotype 1, 2, 3, 4, 5, or 6) Subjects Coinfected With Human Immunodeficiency Virus (HIV)

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis A Hepatitis C

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

• Proportion of treatment-naive subjects with sustained virologic response 12 (SVR12) [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

  SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12 for the treatment-naive HCV genotype 1 subjects coinfected with HIV on the DCV+SOF 12-week regimen

Secondary Outcome Measures:

• Proportion of treatment-naive subjects with SVR12 [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

  SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12 for the treatment-naive HCV genotype 1 subjects coinfected with HIV on the DCV+SOF 8 -week regimen

• Proportion of treatment-experienced HCV subjects with SVR12 [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

  SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12 for the treatment-experienced HCV genotype 1 subjects coinfected with HIV on the DCV+SOF 12-week regimen

• Proportion of HIV/HCV coinfected subjects, in each treatment arm, with SVR12 [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

  SVR12 defined as HCV RNA < LLOQ TD or TND at follow-up Week 12 without regard to infecting HCV genotype

• Safety measured by deaths and the frequency of serious adverse events (SAEs), discontinuations due to adverse events (AEs), Grade 3/4 AEs, and Grade 3/4 laboratory abnormalities [ Time Frame: Up to EOT (Approximately 8/12 weeks depending on treatment regimen) + 7 days ] [ Designated as safety issue: Yes ]

  EOT = End of treatment

• The proportion of subjects coinfected with HIV, in each treatment arm, who achieve HCV RNA < LLOQ-TD/TND [ Time Frame: At Weeks: 1, 2, 4, 6, 8 and 12 (for subjects in the 12-week arm) and EOT; post-treatment Weeks 4 and 24 ] [ Designated as safety issue: No ]
• The proportion of subjects coinfected with HIV, in each treatment arm, who achieve HCV RNA < LLOQ TND [ Time Frame: At Weeks: 1, 2, 4, 6, 8 and 12 (for subjects in the 12-week arm) and EOT ] [ Designated as safety issue: No ]
• The proportion of HIV/HCV coinfected subjects, in each treatment arm, with CC or non-CC genotype at the IL28B rs12979860 single nucleotide polymorphisms (SNPs) who achieve SVR12 [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: February 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1: Cohort 1a-Treatment-naive-12 weeks Daclatasvir 30, 60 or 90 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Sofosbuvir
Experimental: Arm 2: Cohort 1b-Treatment-naive-8 weeks Daclatasvir 30, 60 or 90 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 8 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Sofosbuvir
Experimental: Arm 3: Cohort 2-Treatment Experineced-12 weeks Daclatasvir 30, 60 or 90 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Sofosbuvir

Eligibility

Ages Eligible for Study:  18 Years and older
Genders Eligible for Study:  Both
Accepts Healthy Volunteers:  No

Criteria

Inclusion Criteria:

• Subjects must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications
• Subjects chronically infected with HCV genotype 1, 2, 3, 4, 5 or 6, as documented by positive HCV RNA at screening
• HCV-Treatment-naive subjects
• HCV treatment-experienced subjects are eligible. All permitted prior anti-HCV therapies must be discontinued or completed at least 12 weeks prior to screening
• Subjects must have an HCV RNA ≥ 10,000 IU/mL at Screening
• Subjects must have HIV-1 infection

Exclusion Criteria:

• Presence of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 weeks prior to study entry (AIDS-defining opportunistic infections as defined by the CDC)
• Subjects infected with HIV-2
• Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair
• 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 screening
• Documented or suspected hepatocellular carcinoma (HCC), as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed)
• Evidence of decompensated liver disease including, but not limited to, radiologic criteria,a history or presence of ascites, bleeding varices, or hepatic encephalopathy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02032888

Sponsors and Collaborators
Bristol-Myers Squibb

Investigators
Study Director:
Bristol-Myers Squibb Bristol-Myers Squibb

More Information

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02032888 History of Changes
Other Study ID Numbers: AI444-216
Study First Received: January 9, 2014
Last Updated: January 9, 2014
Health Authority: United States: Food and Drug Administration

-------------------------------------------

Clinical Trial: Phase III Daclatasvir + Sofosbuvir for Genotype 3 Chronic HCV (ALLY 3)

This study is not yet open for participant recruitment.

Verified January 2014 by Bristol-Myers Squibb

Sponsor: Bristol-Myers Squibb

Information provided by (Responsible Party): Bristol-Myers Squibb

ClinicalTrials.gov Identifier: NCT02032901
First received: January 9, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted

Purpose

To study the combination of Daclatasvir and Sofosbuvir for the treatment of HCV Genotype 3 infection

Condition	Intervention	Phase
Hepatitis C	Drug: Daclatasvir Drug: Sofosbuvir	Phase 3

Study Type:
Interventional

Study Design:
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Official Title:
A Phase 3 Evaluation of Daclatasvir and Sofosbuvir in Treatment Naive and Treatment Experienced Subjects With Genotype 3 Chronic Hepatitis C Infection

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

• Proportion of treatment naive subjects with sustained virologic response 12 (SVR12) [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

  SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12

• Proportion of treatment experienced subjects with SVR12 [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

• Safety measured by frequency of serious adverse events (SAEs), discontinuations due to adverse events (AEs), Grade 3/4 AEs, and Grade 3/4 laboratory abnormalities [ Time Frame: Up to end of treatment (EOT) (Week 12) + 7 days ] [ Designated as safety issue: Yes ]
• The proportion of subjects who achieve HCV RNA < LLOQ-TD/TND [ Time Frame: At Weeks: 1, 2, 4, 6, 8 and 12; EOT; post-treatment Weeks 4 and 24 ] [ Designated as safety issue: No ]
• The proportion of subjects who achieve HCV RNA < LLOQ TND [ Time Frame: At Weeks: 1, 2, 4, 6, 8 and 12; EOT ] [ Designated as safety issue: No ]
• The proportion of subjects who achieve SVR12 by baseline cirrhosis (presence or absence) [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]
• The proportion of subjects with CC or non-CC genotype at the IL28B rs12979860 single nucleotide polymorphisms (SNPs) who achieve SVR12 [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: February 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A1:Daclatasvir + Sofosbuvir in treatment-naive subjects Daclatasvir 60 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Sofosbuvir
Experimental: A2:Daclatasvir + Sofosbuvir in treatment-experienced subjects Daclatasvir 60 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Sofosbuvir

Eligibility

Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers:  No

Criteria

Inclusion Criteria:

• Subjects must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications
• Subjects chronically infected with HCV genotype 3
• Subjects who are HCV-Treatment-naive

• Subjects who are HCV-treatment-experienced

  • Previous exposure to non-structural 5A (NS5A) inhibitors is prohibited
• HCV RNA ≥ 10,000 IU/mL at Screening

Exclusion Criteria:

• HCV Genotypes other than genotype (GT) -3 infection; mixed genotype infections are not permitted
• Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair
• 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 screening
• Documented or suspected hepatocellular carcinoma (HCC), as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed)
• Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02032901

Sponsors and Collaborators
Bristol-Myers Squibb

Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

More Information

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02032901 History of Changes
Other Study ID Numbers: AI444-218
Study First Received: January 9, 2014
Last Updated: January 9, 2014
Health Authority: United States: Food and Drug Administration

-----------------------------------

Clinical Trial: A Phase III Evaluation of Daclatasvir + Sofosbuvir in Genotype 1-6 Chronic HCV Subjects With Cirrhosis Who May Require Future Liver Transplant and Subjects Post-Liver Transplant

This study is not yet open for participant recruitment.

Verified January 2014 by Bristol-Myers Squibb

Sponsor: Bristol-Myers Squibb

Information provided by (Responsible Party): Bristol-Myers Squibb

ClinicalTrials.gov Identifier: NCT02032875
First received: January 9, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted

Purpose

This trial is open to patients with cirrhosis due to chronic HCV, and to patients who have already received a liver transplant for chronic HCV. All subjects will be treated with Daclatasvir and Sofosbuvir for 12 weeks. Under certain conditions, the treatment duration may be extended for cirrhotic subjects. The study will test how well this combination of investigational drugs works to treat chronic HCV.

Condition	Intervention	Phase
Hepatitis C	Drug: Daclatasvir Drug: Sofosbuvir Drug: Ribavirin	Phase 3

Study Type:
Interventional

Study Design:
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Official Title:
A Phase 3 Evaluation of Daclatasvir and Sofosbuvir in Genotype 1-6 Chronic Hepatitis C Infection Subjects With Cirrhosis Who May Require Future Liver Transplant and Subjects Post-Liver Transplant

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cirrhosis Hepatitis Hepatitis A Hepatitis C Liver Transplantation

Drug Information available for: Ribavirin

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

• Proportion of genotype (GT) -1 infected Cirrhotic subjects with sustained virologic response (SVR12) [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

  SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) target detected (TD) or target not detected (TND) 12 weeks after end of treatment (EOT)

• Proportion of GT-1 infected Post-transplant subjects with SVR12 [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

  SVR12 defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) target detected (TD) or target not detected (TND) 12 weeks after end of treatment (EOT)

Secondary Outcome Measures:

• The proportion of subjects who achieve SVR12 rates in all Cirrhotic and Post-transplant subjects, respectively, regardless of infecting HCV genotype, and GT-2-6 independently [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]
• Safety measured by frequency of deaths, serious adverse events (SAEs), discontinuations due to adverse events (AEs), Grade 3/4 AEs, and Grade 3/4 clinical laboratory abnormalities [ Time Frame: Up to end of treatment (Week 12 of the treatment phase) + 7 days ] [ Designated as safety issue: Yes ]
• The proportion of subjects who achieve HCV RNA < LLOQ-TD/TND [ Time Frame: At Weeks: 1, 2, 4, 6, 8, 12 and EOT; post-treatment Weeks 4, 8 and 24 ] [ Designated as safety issue: No ]
• The proportion of subjects who achieve HCV RNA < LLOQ TND [ Time Frame: At Weeks: 1, 2, 4, 6, 8, 12 and EOT ] [ Designated as safety issue: No ]
• The proportion of subjects with CC or non-CC genotype at the IL28B rs12979860 single nucleotide polymorphisms (SNPs) who achieve SVR12 in Cirrhotic and Post-transplant subjects respectively [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: March 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1a: Daclatasvir and Sofosbuvir in Cirrhotic subjects Daclatasvir 60 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Sofosbuvir
Experimental: Arm 1b: Daclatasvir+Sofosbuvir+Ribavirin(Relapse Re-treatment) Cirrhotic subjects who undergo transplant while on study treatment may enter an additional Treatment Extension or Relapse Re-treatment period Daclatasvir 60 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks. Ribavirin tablet daily dose of 1000 - 1200 mg orally in two divided doses for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Sofosbuvir Drug: Ribavirin
Experimental: Arm 1c: Daclatasvir and Sofosbuvir (Treatment Extension) Cirrhotic subjects who undergo transplant while on study treatment may enter an additional Treatment Extension or Relapse Re-treatment period Daclatasvir 60 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Sofosbuvir
Experimental: Arm 2: Daclatasvir and Sofosbuvir in Post-transplant subjects Daclatasvir 60 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Sofosbuvir

Eligibility

Ages Eligible for Study:  18 Years and older
Genders Eligible for Study:  Both
Accepts Healthy Volunteers:  No

Criteria

Inclusion Criteria:

• Subjects must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications
• Subjects chronically infected with HCV Genotype 1, 2, 3, 4, 5, or 6 with HCV RNA viral load of ≥ 10,000 IU/mL at screening
• Subjects may be treatment-naïve or treatment-experienced
• Cirrhotic subjects must have cirrhosis confirmed by biopsy, Fibroscan or fibrotest and Aspartate aminotransferase platelet ratio index (APRI) criteria as outlined in the protocol
• Post-transplant subjects must be at least 3 months post-transplant with no evidence of moderate or severe rejection

Exclusion Criteria:

• History of multi-organ transplant, with the exception of dual transplantation of the liver/kidney, is prohibited
• Current or known history of cancer (with the following exceptions: In situ carcinoma of the cervix, adequately treated basal or squamous cell carcinoma of the skin, or hepatocellular carcinoma within Milan criteria for transplantation) within 5 years prior to screening
• Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, or toxin exposures)
• History of HIV infection or chronic hepatitis B virus (HBV) as documented by HBV serologies (e.g., HBsAg-seropositive). Subjects with resolved HBV infection may participate (e.g., HBcAb-seropositive with concurrent HBsAg-seronegative)
• Active hospitalization for decompensated liver disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02032875

Sponsors and Collaborators
Bristol-Myers Squibb

Investigators
Study Director: Bristol-Myers Squibb  Bristol-Myers Squibb

More Information

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02032875 History of Changes
Other Study ID Numbers: AI444-215
Study First Received: January 9, 2014
Last Updated: January 9, 2014
Health Authority: United States: Food and Drug Administration

-----------------------------------------

Beyond phase 3 registration trials: defining safety for triple therapy with protease inhibitors in cirrhosis

Gut doi:10.1136/gutjnl-2013-306480

Editorial

P Ferenci1, G Dusheiko2

+ Author Affiliations

Correspondence toDr Peter Ferenci, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Wien A 1090, Austria;peter.ferenci@meduniwien.ac.at

Received 22 November 2013
Accepted 26 November 2013
Published Online First 13 December 2013

Clinical trials are the standard method for evaluating a new drug for treatment of disease in humans. The phase 3 trial is designed to evaluate a new agent's clinical benefit and possible side effects; as such, it is considered to be the definitive test of the agent's usefulness. While there is no substitute for well-designed phase 3 trials, one should be aware of their limitations.1 Usually, the protocols use very strict selection criteria, creating ‘ideal’ patients, not necessarily reflecting the patient population seen by treating physicians. Good examples were the phase 3 studies for treatment of chronic hepatitis C by triple therapy with peginterferon/ribavirin (PEGIFN/RBV) and a first-generation protease inhibitor (telaprevir or boceprevir). All studies2–5 showed that this treatment augments cure rates substantially but failed to include sufficient patients with the highest need for an effective antiviral therapy, namely patients with advanced cirrhosis.6 In all studies, histologic grades F3 and F4 (according to the METAVIR classification) were grouped as ‘advanced fibrosis’. It should be stressed that F3 is not yet cirrhosis, and F4 is not the same as clinically symptomatic cirrhosis with portal hypertension. …

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Clinical Trial: A Study to Evaluate the Safety and Antiviral Effect of Multiple Doses of ABT-493 and ABT-530 in Adults With Genotype 1 Hepatitis C Virus (HCV)

This study is not yet open for participant recruitment.

Verified November 2013 by AbbVie

Sponsor: AbbVie

Information provided by (Responsible Party): AbbVie

ClinicalTrials.gov Identifier:
NCT01995071
First received: November 21, 2013
Last updated: NA
Last verified: November 2013
History: No changes posted

Purpose

The purpose of this study is to evaluate the safety and antiviral effect of multiple doses of ABT-493 and ABT-530 in adults with genotype 1 HCV.

Condition	Intervention	Phase
Chronic Hepatitis C Hepatitis C Virus Compensated Cirrhosis	Drug: ABT-493 Drug: ABT-530 Drug: ABT-450/r/ABT-267 Drug: ABT-333 Drug: Ribavirin (RBV)	Phase 2

Study Type: Interventional

Study Design:

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Official Title: A Randomized, Open-Label, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-493 and ABT-530 in Adult Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cirrhosis Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by AbbVie:

Primary Outcome Measures:

• Maximal decrease in log10 hepatitis C virus ribonucleic acid levels from baseline [ Time Frame: 3 days after first dose of study drug ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

• The percentage of subjects with sustained virologic response 12 weeks post-treatment [ Time Frame: 12 weeks after last dose of study drug ] [ Designated as safety issue: No ]

  Hepatitis C virus ribonucleic acid less than the lower limit of quantification

• The percentage of subjects with on-treatment virologic failure during the treatment period [ Time Frame: Up to 87 days ] [ Designated as safety issue: No ]

  Percentage of subjects with quantifiable hepatitis C virus ribonucleic acid throughout the entire treatment period, confirmed quantifiable hepatitis C virus ribonucleic acid after previously having unquantifiable hepatitis C virus ribonucleic acid, or a confirmed increase of at least one log10 in hepatitis C virus ribonucleic acid during treatment

• The percentage of subjects with post-treatment relapse [ Time Frame: Within 12 weeks after the last dose of study drug ] [ Designated as safety issue: No ]

  Percentage of subjects with confirmed quantifiable hepatitis C virus ribonucleic acid among subjects with unquantifiable hepatitis C virus ribonucleic acid at the end of treatment

Estimated Enrollment: 80
Study Start Date: November 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1 ABT-493 Dose A for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-493 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet
Experimental: Arm 2 ABT-493 Dose B for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-493 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet
Experimental: Arm 3 ABT-493 Dose C for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-493 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet
Experimental: Arm 4 ABT-493 Dose D for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-493 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet
Experimental: Arm 5 ABT-493 Dose E for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-493 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet
Experimental: Arm 6 ABT-530 Dose A for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-530 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet
Experimental: Arm 7 ABT-530 Dose B for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-530 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet
Experimental: Arm 8 ABT-530 Dose C for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-530 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet
Experimental: Arm 9 ABT-530 Dose D for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-530 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet
Experimental: Arm 10 ABT-530 Dose E for 3 days, followed by ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks	Drug: ABT-530 tablet Drug: ABT-450/r/ABT-267 tablet Drug: ABT-333 tablet Drug: Ribavirin (RBV) tablet

Eligibility

Ages Eligible for Study: 18 Years to 70 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Chronic HCV infection prior to study enrollment.
• Screening laboratory result indicating HCV genotype 1-infection.
• Subject has plasma HCV RNA level greater than 10,000 IU/mL at Screening.
• Per local standard, subject is considered to be non-cirrhotic or to have compensated cirrhosis.

Exclusion Criteria:

• History of severe, life-threatening or other significant sensitivity to any drug.
• Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency Virus antibody (HIV Ab).
• Prior therapy for the treatment of HCV.
• Any current or past clinical evidence of Child Pugh B or C classification of clinical history of liver decompensation including ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy.
• Any cause of liver disease other than chronic HCV infection.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01995071

Contacts

Contact: Christian Naylor, BS
847-935-2492
christian.naylor@abbvie.com

Contact: Mary Santangelo, BS
847-938-6703
mary.santangelo@abbvie.com

Sponsors and Collaborators AbbVie

Investigators Study Director: Armen Asatryan, MD AbbVie

More Information

No publications provided

Responsible Party: AbbVie

ClinicalTrials.gov Identifier: NCT01995071 History of Changes

Other Study ID Numbers: M13-595

Study First Received: November 21, 2013

Last Updated: November 21, 2013

Health Authority: United States: Food and Drug Administration