Clinical trial NCT01821625: Study of Quadruple Therapy With Eltrombopag for Chronic Hepatitis C
Official title: Study of Quadruple Therapy With Eltrombopag for Chronic Hepatitis C
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Thrombocytopenia
Hepatitis C
Keywords: Thrombocytopenia
Hepatitis
Platelets
Eltrombopag
Liver Disease
Antiviral Treatment
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2013-04-01
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Percentage of Study Patients Completing Antiviral Therapy, as Per Boceprevir Prescribing Guidelines.
timeFrame: Up to 56 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: William M Lee, M.D.
role: PRINCIPAL_INVESTIGATOR
References: