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Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01636778
First received: July 5, 2012
Last updated: October 23, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to assess the ability of SB-497115-GR to raise platelet counts in thrombocytopenic patients with hepatitis C virus (HCV) infection (platelet count <80,000 /μL, suggestive of compensated cirrhosis) to a level desirable to initiate antiviral therapy and to assess the ability of SB-497115-GR to maintain platelet counts at a level sufficient to minimise dose reductions of pegylated interferon (Peg-IFN) and ribavirin (RBV) therapy with the expectation that a lower rate of Peg-IFN dose reduction and omission will translate to a higher rate of sustained viral response.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: SB-497115-GR
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Non-randomised, Open Label, Multi-centre Phase II Study to Assess the Efficacy and Safety of SB-497115-GR in Thrombocytopenic Subjects With Chronic Hepatitis C and Compensated Liver Cirrhosis.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Platelet count in Part 1 [ Time Frame: 1 - 9 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with platelet count more than or equal to 100,000 /μL.

  • Platelet count in Part 2 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects whose platelet counts sustained more than or equal to 50,000 /μL throughout Part 2


Secondary Outcome Measures:
  • Changes in platelet counts [ Time Frame: 49 - 57 weeks ] [ Designated as safety issue: No ]
    Changes in platelet counts throughout the study period

  • Compliance to concurrent agents [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    The proportion of subjects who required dose reduction or interruption of Pegylated interferon and ribavirin therapy in Part 2

  • Adherence to concurrent agents [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    The proportion of subjects who had adhered to Pegylated interferon and ribavirin therapy by more than or equal to 80% in Part 2

  • Antiviral effect [ Time Frame: 73 - 81 weeks ] [ Designated as safety issue: No ]
    Proportions of subjects achieving undetectable HCV RNA after 24 weeks of Pegylated interferon and ribavirin therapy

  • Antiviral effect at time points [ Time Frame: 4, 12, 24, 36 and 48 weeks after initiation of Part 2 ] [ Designated as safety issue: No ]
    Antiviral effect at every evaluation points of Pegylated interferon and ribavirin therapy

  • Safety outcomes [ Time Frame: 49 - 57 weeks ] [ Designated as safety issue: Yes ]
    Frequency and grade of adverse events (including abnormal laboratory values) observed

  • Pharmacokinetic parameters [ Time Frame: pre-dose, 1, 2, 4, 6, 8 and 24 hours after dosing on Day 14 of Part 1 ] [ Designated as safety issue: No ]
    Concentration-time data, Cmax, tmax, AUC(0-t) and AUC(0-tau) will be determined

  • Thrombopoietin (TPO) levels [ Time Frame: Baseline, Day 1 of Part 2 and every 24 weeks afterward, 4 weeks after end of treatment ] [ Designated as safety issue: No ]
    Plasma TPO levels


Enrollment: 45
Study Start Date: July 2012
Estimated Study Completion Date: November 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SB-497115-GR
investigational product for thrombocytopenia
Drug: SB-497115-GR
TPO receptor agonist to increase platelet count

  Eligibility

Ages Eligible for Study:   20 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subject is able to understand and comply with protocol requirements and instructions and is likely to complete the study as planned, as well as provided a written consent.

  • A subject age between ≥20 and <75 years at time of informed consent.
  • A subject who applies to one of the following:

Female subject with non-childbearing potential [i.e., physiologically incapable of becoming pregnant, who: has had a hysterectomy, or had a bilateral oophorectomy (ovariectomy), or had a bilateral tubal ligation, or is post-menopausal for greater than one year].

Female subject with childbearing potential, has a negative urine or serum pregnancy test at screening and within the 24-hour period prior to the first dose of SB-497115-GR, and completely abstains from intercourse or agree to use two of the following acceptable methods of contraception for 14 days before exposure to SB-497115-GR, throughout the clinical trial, and for 24 weeks after completion or premature discontinuation from the study.

Intrauterine device or intrauterine system that meets the effectiveness criteria as stated in the product label.

Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject.

Double-barrier contraception (condom with spermicidal jelly, or diaphragm with spermicide).

Male subject with childbearing potential partner completely abstains from intercourse or agree to use condom and diaphragm with spermicide.

  • Subjects who were diagnosed as hepatitis C or compensated liver cirrhosis (Child-Pugh class A) without hepatic encephalopathy, or ascites. If there is a clear cirrhosis, treatment should be given with care as there is a potential of progressing to liver failure.
  • Subjects who, in the opinion of the investigator, are appropriate candidates for Peg-IFN and RBV combination therapy for 48 weeks.
  • HCV positive by TaqMan test at screening.
  • Subject who fulfil all the organ functions below.

Items Values Platelet <80,000 /μL Haemoglobin ≥12.0 g/dL* Absolute neutrophil count (ANC) ≥1500 /μL* Creatinine clearance >50 mL/minute Total bilirubin <2.0 mg/dL Albumin >3.0 g/dL Prothrombin time >60%

*If the investigators consider the values are sufficient to give Peg-IFN/RBV, then a subject can be enrolled upon consulting the Medical Monitor.

Exclusion Criteria:

  • Subject who relapsed or did not respond after 48 weeks of Peg-IFN/RBV therapy had been given with sufficient dose previously.
  • Subject with history of IFN (including Peg-IFN) therapy or Peg-IFN/RBV therapy, but could not been treated with optimal Peg-IFN/RBV therapy due to the reasons other than thrombocytopenia.
  • Subject who received IFN therapy (including Peg-IFN), antiviral therapy (excluding oseltamivir phosphate, etc.), immuno-modulatory treatment, radiotherapy or phlebotomy within 3 months (90 days) prior to the first dose of SB-497115-GR.
  • Treatment with an investigational drug within 30 days prior to the first dose of SB-497115-GR or 5 half-lives of that investigational drug (whichever is longer).
  • Subject with decompensated liver disease.
  • Chronic liver disease other than chronic hepatitis C (e.g., autoimmune hepatitis, alcohol-induced hepatitis, drug-induced hepatitis, etc.).
  • Subject with idiopathic thrombocytopenic purpura or active autoimmune disease.
  • Subject who have had a malignancy diagnosed and/or treated within the past 5 years.
  • Subjects who require endoscopic treatment for varices or documented history of clinically significant bleeding from oesophageal or gastric varices.
  • Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin.
  • Subject with serious cardiac, cerebrovascular, chronic pulmonary disease or interstitial lung disease, or documented history of any of these diseases.
  • Pre-existing cardiac disease (congestive heart failure in New York Heart Association Grade III/IV), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTcF >450 msec or if with bundle brunch block, QTcF >480 msec.
  • Subject with depression, psychiatric disorder requiring treatment or suicidal ideation or suicide attempt history, or history of these.
  • Subject with uncontrolled hypertension (≥160 mmHg systolic or ≥100 mmHg diastolic).
  • Subject with diabetes mellitus that can not be controlled by treatment.
  • Thyroid dysfunction not adequately controlled.
  • Subjects with haemoglobinopathies.
  • History or current condition of seizure disorder.
  • Subject who was positive for Human Immunodeficiency Virus (HIV) antibody or Hepatitis B Virus (HBV) antigen.
  • Subject with arterial or venous thrombosis history or evidence of portal vein thrombosis on abdominal imaging (e.g., by computerized tomography or magnetic resonance imaging) within 3 months.
  • History of alcohol/drug abuse or dependence.
  • History of platelet clumping that prevents reliable measurement of platelet counts.
  • Subjects planning to have cataract surgery.
  • History of major organ transplantation.
  • Known hypersensitivity to SB-497115-GR ingredients, IFN (including Peg-IFN), nucleoside analogues or biological agents (i.e., vaccines).
  • Pregnant or nursing women or a male subject with pregnant partner.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01636778

Locations
Japan
GSK Investigational Site
Aichi, Japan, 467-8602
GSK Investigational Site
Fukui, Japan, 918-8503
GSK Investigational Site
Fukuoka, Japan, 803-8505
GSK Investigational Site
Fukuoka, Japan, 830-0011
GSK Investigational Site
Gunma, Japan, 370-0829
GSK Investigational Site
Hyogo, Japan, 663-8501
GSK Investigational Site
Ibaraki, Japan, 317-0077
GSK Investigational Site
Kagawa, Japan, 760-0017
GSK Investigational Site
Kagawa, Japan, 760-8557
GSK Investigational Site
Kagoshima, Japan, 899-5112
GSK Investigational Site
Kanagawa, Japan, 213-8587
GSK Investigational Site
Nagasaki, Japan, 856-8562
GSK Investigational Site
Oita, Japan, 879-5593
GSK Investigational Site
Osaka, Japan, 540-0006
GSK Investigational Site
Tokyo, Japan, 105-8470
GSK Investigational Site
Wakayama, Japan, 646-8558
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01636778     History of Changes
Other Study ID Numbers: 116101
Study First Received: July 5, 2012
Last Updated: October 23, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
Hepatitis C, chronic
Thrombocytopenia

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 20, 2014