SQUELCH-C: Study of Quadruple Therapy with Eltrombopag for Chronic Hepatitis C

Study ID
STU 032013-020

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Paola Piovanetti
214-645-6187
paola.piovanetti@utsouthwestern.edu

Principal Investigator
William Lee

Summary

SQueLCH-C is an investigator-initiated, single arm, non-blinded pilot study on the use of eltrombopag in combination with ribavirin, interferon, and boceprevir, for patients with low platelets who would not otherwise be treatment candidates because of low platelet counts. in order to compute statistical efficacy, the control group will have a theoretical estimation of 5% for completion of therapy, even though in each case therapy would typically be prohibited altogether due to low platelet levels. We choose not to use an experimental control group because it is unethical and contraindicated to treat an advanced thrombocytopenic patient without platelet support.

administration of the drugs ribavirin and boceprevir will be standard of care, with one exception for interferon. The platelet level cut offs for dose reductions will be lowered as described in Table 7-1 in Section 7.1.2 of protocol (page 28).

Study group (minimum n [?] 30): eltrombopag + ribavirin + interferon + boceprevir for up to 56 weeks weeks or eLT + RBV + iFn + SoF for up to 24 weeks. Therapy length will be response guided and may vary between patients for BoC therapy.

only uT Southwestern and Parkland will be used to enroll patients.

approximately 50 subjects will be consented, for a minimum of 30 patients enrolled.

The maximum time a subject is expected to be enrolled in the study will depend upon their response to treatment, and underlying liver disease severity. Screening, treatment, and treatment follow-up will require a maximum of 84 weeks.

Primary endpoint
* SVR rate of 44% at 6 months after completion of therapy.

Secondary endpoints

* Percentage of patients completing therapy as per BoC response-guided therapy guidelines or SoF therapy guidelines, comparing 5% (null hypothesis for spontaneous clearance) and an expected minimum of 25% completion in these advanced liver disease patients.
* other descriptive measurements will include side effects, number of bleeding events and number of iFn and RBV reductions encountered.

Participant Eligibility


* Male and female patients at least 18 years of age.

* Require a platelet count
a. < 75 x 109 /L at time of screening.
b. >75 x 109 /L and < 125 x 109 /L and a history of prior anti-HCV with IFN/RBV with early termination due to decreased platelet counts

* The patients must meet the eligibility criteria for all drugs involved in the study: ELT, RBV, IFN, and BOC or SOF.

* Only genotype 1 (a, b, indeterminate, or mixed) will be included and genotype 4 will be included in the study to received SOF.
o Prior treatment with IFN, RBV, Boceprevir and/ or Telaprevir will not be exclusion criteria.

* Confirmed history of chronic hepatitis C
o This will be confirmed via a positive anti-HCV antibody, positive HCV RNA, or positive HCV genotyping test with evidence of chronic infection, including biopsy, or imaging showing cirrhosis.

* Cirrhotic patients who are not decompensated will be included:
o The presence of cirrhosis will be determined by sonogram or radiologic test of equivalent or greater sensitivity.

* Liver imaging within 1 year to exclude hepatocellular carcinoma (HCC) is required in patients with cirrhosis.
o Subjects with a prior history of HCC that have had extirpative therapy and have no evidence of recurrence upon imaging within 3 months of screening will be considered eligible for study enrollment.
o Subjects listed for liver transplantation are eligible for enrollment if their condition meets other criteria: Child A without evidence of decompensation, HCC treated as above.
o We will also require 4 sonograms (for subjects on boceprevir therapy) for evidence of portal vein thrombosis: one prior to treatment and at 4-6 months[Single Quote] on treatment with quadruple therapy, completion of treatment and completion of follow up. Three or four sonograms will be required for patients on SOF therapy x one prior to treatment, at completion of quadruple therapy and at completion of follow up. A sonogram at Week 12 will be required if SOF subjects receive 24 weeks of antiviral therapy.

* Patients without evidence of cirrhosis but meeting platelet criteria will also be admitted to study.

* Female subjects are eligible if
o Non-pregnant,
o Non-childbearing potential, or
o 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).
o They must also be willing to have pregnancy tests performed every 4-weeks until 6 months after completion of RBV.

* 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 RBV therapy.

* 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 the RBV, IFN, and BOC or SOF will also be required.
o This may be covered by insurance, out of pocket, or other payment plan