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

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01821625
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 7
• Location: 1
• Arm: 1
• Actual Duration (Months): 36
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Thrombocytopenia; Hepatitis C	Drug: Eltrombopag	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of Quadruple Therapy With Eltrombopag for Chronic Hepatitis C
• Actual Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Drug: 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.; Other Names: Promacta

Outcome Measures

Primary Outcome Measures

1. 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: Study patient's liver disease status. Study patient's antiviral response. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT Southwestern Medical Center	Dallas	Texas	United States	75390-8887

Sponsors and Collaborators

• University of Texas Southwestern Medical Center
• GlaxoSmithKline

Investigators

• Principal Investigator: William M Lee, M.D., UT Southwestern Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT01821625
• Other Study ID Numbers: STU 032013-020
• First Posted: Apr 1, 2013
• Last Update Posted: Nov 13, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by University of Texas Southwestern Medical Center: Thrombocytopenia; Hepatitis; Platelets; Eltrombopag; Liver Disease; Antiviral Treatment
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Thrombocytopenia

Study Results

Participant Flow

Arm/Group Title	Thrombocytopenic (Low Platelet) Patients
Arm/Group Description	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.
Period Title: Overall Study
STARTED	7
COMPLETED	1
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Thrombocytopenic (Low Platelet) Patients
Arm/Group Description	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.
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 100%
>=65 years	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	5 71.4%
Male	2 28.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 28.6%
Not Hispanic or Latino	5 71.4%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Study Patients Completing Antiviral Therapy, as Per Boceprevir Prescribing Guidelines.
Description	The length of therapy will depend on several factors: Study patient's liver disease status. Study patient's antiviral response. 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thrombocytopenic (Low Platelet) Patients
Arm/Group Description	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.
Measure Participants	7
Count of Participants [Participants]	1 14.3%

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	No unusual collection of adverse events.
Arm/Group Title	Thrombocytopenic (Low Platelet) Patients
Arm/Group Description	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. One subject completed the study as planned. Four subjects had to drop out of the study early for different reasons. One subject was not able to start the hepatitis C triple therapy medications due to a medical condition, two subjects discontinued due to lack of virologic response and one subject discontinued treatment due to side effects.
All Cause Mortality
	Thrombocytopenic (Low Platelet) Patients
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Thrombocytopenic (Low Platelet) Patients
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Thrombocytopenic (Low Platelet) Patients
	Affected / at Risk (%)	# Events
Total	3/7 (42.9%)
Gastrointestinal disorders
Variceal hemorrhage	1/7 (14.3%)	1
Nervous system disorders
Flu like symptoms	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
Skin ulcer	1/7 (14.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.