Phase 2 N=45 Treatment

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

Hepatitis C, Chronic

Bottom Line

View on ClinicalTrials.gov: NCT01636778 ↗

Enrolled (actual)

Serious AEs

5.5%

Results posted

Feb 2015

Primary outcome: 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 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: SB-497115-GR (Drug)
Age: Adult, Older Adult · 20+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: May 2014

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	—

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.

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.

View full record on ClinicalTrials.gov →

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.