Hepatitis C, Thrombocytopenia
Conditions
Keywords
Thrombocytopenia, Hepatitis, Platelets, Eltrombopag, Liver Disease, Antiviral Treatment
Brief summary
This study will provide chronic hepatitis C patients with low platelets (less than 75x10\^9/L) the opportunity to undergo treatment and possible cure of their virus. The main hepatitis C drugs will be administered as standard of care, with the addition of the study drug eltrombopag. The investigators hypothesize that providing eltrombopag to chronic hepatitis C patients with low platelets (less than 75x10\^9/L) will permit the initiation and completion of antiviral triple therapy with boceprevir, ribavirin, and pegylated-interferon.
Detailed description
SQUELCH-C is an investigator-initiated, single arm, non-blinded pilot study on the use of eltrombopag in combination with ribavirin, pegylated-interferon, and boceprevir, for patients who would not otherwise be treatment candidates because of low platelet counts (less than 75x10\^9/L). Administration of the drugs ribavirin and boceprevir will be standard of care, with one exception for interferon. The total drug treatment period for the study patient will range from 32 - 56 weeks, depending on liver disease stage and viral response. Follow-up will take place at 12 and 24 weeks post treatment to evaluate for sustained viral response. Total study participation may require 1.5 years.
Interventions
DRUGEltrombopag
Study patients will be provided eltrombopag to raise platelet levels before anti-hepatitis C drugs are initiated, and will continue eltrombopag throughout the study.
Sponsors
GlaxoSmithKline
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients at least 18 years of age. * Require a platelet count below 75 x 10\^9 /L at time of screening. * The patients must meet the eligibility criteria for all drugs involved. * Only genotype 1 (a, b, indeterminate, or mixed). * Confirmed history of chronic hepatitis C. * Cirrhotic patients will be included. * Liver imaging within 1 year to exclude hepatocellular carcinoma (HCC) is required in patients with cirrhosis. * Patients without evidence of cirrhosis but meeting platelet criteria will also be admitted to study. * Subjects must be able to provide informed consent, comply with drug administration instructions, and be able to complete each study visit. * Ability to cover costs of ribavirin, interferon, and boceprevir will also be required. * Female subjects are eligible if: Non-pregnant, non-childbearing potential, or of childbearing potential and willing to perform complete abstinence or correctly use a form of birth control during intercourse \[barrier method, intrauterine device, hormonal therapy, or surgical sterilization in females or male partner\]. They must also be willing to have pregnancy tests performed every 4- weeks until 6 months after completion of ribavirin. * Male study participants must agree to use a condom and their female partner must partake in one of the contraceptive methods discussed above until 6 months after completion of ribavirin therapy.
Exclusion criteria
* A history of chronic infection (i.e., HIV or HBV) or a previous organ transplantation. * A history of a platelet disorder. * A poorly controlled underlying medical illness (i.e., diabetes, hypertension, coronary artery disease, congestive heart failure, etc.). * Any contraindication to any study drugs as mentioned in their respective prescribing information. * Patients with decompensated cirrhosis defined as current evidence for ascites, encephalopathy, infection or variceal bleeding. All patients should be considered Child-Pugh Class A. * Patients with aminotransferase levels ≥ 500 IU/L will be excluded on presumption of another active liver disease. * Patients must not be pregnant or nursing. * The study physician maintains the right to exclude a patient for a medical condition not listed above or based off laboratory values indicating chronic disease discovered at screening. * Patients with eye disease may be excluded from this study if the ophthalmologist does not recommend treatment. * Subjects with known hypersensitivity reactions (such as Stevens-Johnson syndrome, toxic, epidermal necrolysis, and erythema multiforme to ribavirin) to study drugs or any component of the products. * Subjects with autoimmune hepatitis, hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), creatinine clearance less than 50 mL/min. * Co-administration of drugs that are highly dependent on CYP3A4/5 for clearance and CYP3A4/5 inducers (See Table 2 in boceprevir prescribing information).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Study Patients Completing Antiviral Therapy, as Per Boceprevir Prescribing Guidelines. | Up to 56 weeks | The length of therapy will depend on several factors: 1. Study patient's liver disease status. 2. Study patient's antiviral response. 3. Study patient's tolerance to treatment. One patient completed therapy and experienced a sustained viral response. A minimum full course of treatment will be 30 weeks, with a maximum of 56 weeks of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Thrombocytopenic (Low Platelet) Patients All study patients will undergo intervention in this study.
The intervention will be a lead-in with eltrombopag and antiviral triple therapy (interferon, ribavirin and boceprevir).
Eltrombopag: Study patients will be provided eltrombopag to raise platelet levels before anti-hepatitis C drugs are initiated, and will continue eltrombopag throughout the study. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Medical contraindication | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Thrombocytopenic (Low Platelet) Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 53 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 3 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Percentage of Study Patients Completing Antiviral Therapy, as Per Boceprevir Prescribing Guidelines.
The length of therapy will depend on several factors: 1. Study patient's liver disease status. 2. Study patient's antiviral response. 3. Study patient's tolerance to treatment. One patient completed therapy and experienced a sustained viral response. A minimum full course of treatment will be 30 weeks, with a maximum of 56 weeks of treatment.
Time frame: Up to 56 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Thrombocytopenic (Low Platelet) Patients | Percentage of Study Patients Completing Antiviral Therapy, as Per Boceprevir Prescribing Guidelines. | 1 Participants |