Phase 2
Completed N=45
Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients
Hepatitis C, Chronic
Source: ClinicalTrials.gov NCT01636778 ↗
Enrolled (actual)
45
Serious AEs
5.5%
Results posted
Feb 2015
Primary outcomePrimary: Number of Participants Whose Platelet Count Increased From a Baseline Count of < 80 Gi/L to a Count >=100 Gi/L During Part 1 — 43 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Whose Platelet Count Increased From a Baseline Count of < 80 Gi/L to a Count >=100 Gi/L During Part 1 |
43 | — |
| PRIMARY Number of Participants Whose Platelet Counts Maintained at >=50 Gi/L During Part 2 |
36 | — |
| SECONDARY Median Platelet Count at the Indicated Time Points in Part 1 |
63.0; 74.0; 100.0; 97.0; 104.0; 87.0 | — |
| SECONDARY Time in Weeks to Achieve Platelet Count >= 100 Gi/L |
11; 25; 5; 1; 0; 1 | — |
| SECONDARY Median Platelet Count at the Indicated Time Points in Part 2 |
114.0; 106.5; 118.0; 89.0; 86.0; 79.5 | — |
| SECONDARY Median Platelet Count at the Indicated Time Points During Follow-up Period After Part 2 |
86.5; 82.5; 70.0; 63.0 | — |
| SECONDARY Minimum Platelet Count on Antiviral Therapy |
0; 5; 34; 2; 0; 0 | — |
| SECONDARY Dose of Eltrombopag That Enabled Initiation of Antiviral Therapy |
1; 25; 13; 0; 2; 4 | — |
| SECONDARY Number of Antiviral Therapy Dose Reductions in Part 2 |
8; 9; 10; 3; 2; 1 | — |
| SECONDARY Number of Participants With the Indicated Levels of Peg-IFN Alpha-2a Therapy Dose Reductions in Part 2 |
4; 6; 4; 1; 1 | — |
| SECONDARY Number of Participants With the Indicated Levels of Peg-IFN Alpha-2b Therapy Dose Reductions in Part 2 |
16; 2; 4; 0; 3 | — |
| SECONDARY Number of Participants With the Indicated Levels of RBV Therapy Dose Reductions in Part 2 |
14; 12; 9; 3; 3 | — |
| SECONDARY Time to First Dose Reduction of Antiviral Therapy in Part 2 |
9.44; 6.22; 9.16 | — |
| SECONDARY Number of Participants Who Discontinued Antiviral Therapy in Part 2 |
8 | — |
| SECONDARY Number of Participants Who Discontinued Peg-IFN Alpha-2a Therapy in Part 2 |
1 | — |
| SECONDARY Number of Participants Who Discontinued Peg-IFN Alpha-2b Therapy in Part 2 |
7 | — |
| SECONDARY Number of Participants Achieving Adherence to Antiviral Therapy in Part 2 |
32 | — |
| SECONDARY Number of Participants Achieving Adherence to Peg-IFN Alpha 2a Antiviral Therapy in Part 2 |
14 | — |
| SECONDARY Number of Participants Achieving Adherence to Peg-IFN Alpha-2b Antiviral Therapy in Part 2 |
18 | — |
| SECONDARY Number of Participants With Sustained Virologic Response (SVR) in Part 2 |
9 | — |
| SECONDARY Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) in Part 2 |
6; 5 | — |
| SECONDARY Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) in Part 2 |
28; 18 | — |
| SECONDARY Number of Participants With End of Treatment Response (ETR) for Undetectable HCV RNA at the End of Peg-IFN/RBV Treatment in Part 2 |
19 | — |
| SECONDARY Mean Serum HCV RNA at the Indicated Time Points In Part 2 |
6.41; 6.37; 3.77; 2.52; 2.46; 2.69 | — |
| SECONDARY Mean Serum HCV RNA at the Indicated Time Points During Follow-up Period After Part 2 |
3.10; 5.04; 4.82 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part1 |
13; 0; 0; 4; 0; 0 | — |
| SECONDARY Number of Participants With Any AE and Any SAE in Part 2 |
41; 3; 0; 41; 9; 3 | — |
| SECONDARY Number of Participants With Any AE and Any SAE During Follow-up Period After Part 2 |
25; 4; 0; 6; 0; 0 | — |
| SECONDARY Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 With Follow-up Period |
0.9; -1.7; 2.8; -2.8; -1.0; -4.0 | — |
| SECONDARY Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 2 |
0.2; -5.9; -8.7; -5.2; -3.9; -6.0 | — |
| SECONDARY Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During Follow-up Period After Part 2 |
126.5; 125.4; 126.7; 128.4; 73.8; 74.3 | — |
| SECONDARY Mean Change From Baseline in Heart Rate at the Indicated Time Points in Part 1 With Follow-up Period |
0.1; -0.1; 0.1; 2.8; 0.3; 2.0 | — |
| SECONDARY Mean Change From Antiviral Baseline in Heart Rate at the Indicated Time Points in Part 2 |
0.4; -3.5; 1.0; 3.9; 5.9; 4.7 | — |
| SECONDARY Mean Heart Rate at the Indicated Time Points During Follow-up Period After Part 2 |
78.3; 79.5; 74.0; 74.6 | — |
| SECONDARY Mean Change From Baseline in Weight at the Indicated Time Points in Part 1 With Follow-up Period |
0.09; 0.05; 0.75; 1.15; 1.00; 1.03 | — |
| SECONDARY Mean Change From Baseline in Weight at the Indicated Time Points in Part 2 |
0.04; -0.95; -1.14; -1.04; -1.05; -1.28 | — |
| SECONDARY Mean Weight at the Indicated Time Points During Follow-up Period After Part 2 |
55.77; 56.37; 57.05; 57.84 | — |
| SECONDARY Mean Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 With Follow-up Period |
-0.04; 0.03; 0.06; 0.07; -0.07; -0.10 | — |
| SECONDARY Mean Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 |
0.08; 0.09; 0.17; 0.16; 0.19; 0.22 | — |
| SECONDARY Mean Body Temperature at the Indicated Time Points During Follow-up Period After Part 2 |
36.44; 36.37; 36.29; 36.90 | — |
| SECONDARY Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points in Part 1 With Follow-up Periodc |
0.03; 0.02; 0.26; 0.39; 0.36; 0.36 | — |
| SECONDARY Mean Change From Baseline in BMI at the Indicated Time Points in Part 2 |
0.01; -0.37; -0.44; -0.41; -0.42; -0.51 | — |
| SECONDARY Mean BMI at the Indicated Time Points During Follow-up Period After Part 2 |
21.89; 22.11; 22.37; 22.54 | — |
| SECONDARY Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per Division of Acquired Immunodeficiency Syndrome (DAIDS) in Part 1 |
5; 5; 0; 0; 0; 4 | — |
| SECONDARY Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per DAIDS in Part 2 |
18; 15; 3; 0; 0; 3 | — |
| SECONDARY Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per DAIDS During Follow-up Period After Part 2 |
3; 2; 1; 0; 0; 5 | — |
| SECONDARY Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters Per DAIDS in Part 1 |
1; 1; 0; 0; 0; 4 | — |
| SECONDARY Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters Per DAIDS in Part 2 |
38; 3; 11; 24; 0; 26 | — |
| SECONDARY Number of Participants With the Indicated Shifts From BL in Severity Grades for Hematology Parameters Per DAIDS During Follow-up Period After Part 2 |
2; 2; 0; 0; 0; 2 | — |
| SECONDARY Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part1 With Follow Up Period |
6; 39; 4; 1; 1; 6 | — |
| SECONDARY Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part 2 |
5; 36; 1; 5; 33; 2 | — |
| SECONDARY Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points During Follow-up Period After Part 2 |
3; 34; 1; 1; 3; 32 | — |
| SECONDARY Number of Participants Assessed as Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at the Indicated Time Points |
31; 14; 0; 26; 14; 1 | — |
| SECONDARY Number of Participants Assessed as Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) During Follow-up After Part 2 |
24; 13; 0; 31; 6; 0 | — |
| SECONDARY Number of Participants With Abdominal Ultrasound With Doppler at the Indicated Time Points |
0; 0; 0; 43; 8; 1 | — |
| SECONDARY Number of Participants With Abdominal Ultrasound With Doppler During Follow-up Period After Part 2 |
1; 1; 0; 36; 4 | — |
| SECONDARY Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler in the Study |
11.5; 4.7; 11.5; 4.9; 11.6; 4.5 | — |
| SECONDARY Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler During Follow-up Period After Part 2 |
11.0; 4.4 | — |
Eligibility 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 50 mL/minute Total bilirubin 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.
Data sourced from ClinicalTrials.gov (NCT01636778). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.