A Registry for Participants With Cirrhosis Who Achieve a Sustained Virologic Response Following Treatment With a Sofosbuvir-Based Regimen Without Interferon for Chronic Hepatitis C Infection

A Registry for Subjects With Cirrhosis Who Achieve a Sustained Virologic Response Following Treatment With a Sofosbuvir-Based Regimen Without Interferon for Chronic Hepatitis C Infection

Status

Terminated

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02292706

Enrollment

1609

Registered

2014-11-17

Start date

2014-12-29

Completion date

2021-12-31

Last updated

2023-10-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C Virus Infection

Keywords

HCV Cirrhosis registry, Cirrhosis, Hepatitis C

Brief summary

The primary objective of this registry study is to assess the durability of sustained virologic response (SVR) and clinical progression or regression of liver disease including the incidence of hepatocellular carcinoma following SVR in participants with cirrhosis after treatment with a sofosbuvir-based regimen for HCV infection.

Interventions

DRUGSofosbuvir

Exposure of interest for participants who received sofosbuvir in a previous Gilead study for chronic HCV infection.

DRUGRibavirin

DRUGLDV/SOF

Exposure of interest for participants who received LDV/SOF in a previous Gilead study for chronic HCV infection.

DRUGSOF/VEL

Exposure of interest for participants who received SOF/VEL in a previous Gilead study for chronic HCV infection.

DRUGSOF/VEL/VOX

Exposure of interest for participants who received SOF/VEL/VOX in a previous Gilead study for chronic HCV infection.

DRUGOther SOF-Based Regimen

The other SOF-based regimens may have included the following: * BMS-790052 (Daclatasvir) + GS-7977 (SOF) with or without RBV * LDV/SOF + GS-9669, GS-7977 (SOF) + with or without RBV + TMC-435 (Simeprevir) * LDV/SOF + Vedroprevir (VDV), LDV/SOF + GS-9669 (250 mg and 500 mg) * LDV/SOF + VDV + RBV * Simeprevir + SOF * TMC-435 (Simeprevir) + VEL/SOF

OTHERIneligible parent treatment

Participants were enrolled from ineligible parent treatment group.

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Willing and able to provide written informed consent * Have either previously participated in a Gilead-sponsored HCV study and received a sofosbuvir-containing regimen without interferon OR at pre-selected sites only, have received an all-oral SOF-based regimen outside a clinical study. These individuals must have documentation of the regimen, start and end of treatment dates (month and year), and of having achieved SVR12. * Have achieved SVR either in a Gilead-sponsored study, as defined in the treatment protocol OR for individuals who enroll after receiving an all-oral SOF-based regimen outside a clinical study, SVR will be defined as HCV RNA \< lower limit of quantification (LLOQ) approximately 12 weeks following last dose of treatment. * Have liver cirrhosis, as defined in the treatment protocol, and have not had a liver transplant after receiving a SOF-containing regimen OR individuals who enroll after receiving an all-oral SOF-based regimen outside a clinical study, will have had cirrhosis confirmed prior to initiation of HCV treatment. Key

Exclusion criteria

* Individuals planning to initiate a new course of HCV therapy, including approved products and any investigational agents, during the course of this Registry * History of clinically-significant illness or any other major medical disorder that may interfere with the follow-up, assessments, or compliance with the protocol Note: Other protocol defined Inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240	Week 240	SVR at Week 240 was defined as HCV RNA\< lower limit of quantification (LLOQ i.e., 15 or 25 international units per milliliter \[IU/mL\]) or last available HCV RNA\< LLOQ with no subsequent follow-up values at Week 240 after enrollment in this registry study. Percentage of participants who maintained SVR status by Week 240 was estimated using a Kaplan-Meier model.
Percentage of Participants With Any Liver-Associated Events	Enrollment up to 240 weeks	The percentage of participants with any liver-associated events since registry start (enrollment) through Week 240 was estimated using a Kaplan-Meier model.
Percentage of Participants Who Developed Hepatocellular Carcinoma (HCC) Through Week 240	Enrollment up to 240 weeks	Participants with de novo HCC since registry start were defined as participants who had not been identified with HCC prior to registry start and only had HCC since registry start. The percentage of participants who developed de novo HCC through Week 240 was estimated using a Kaplan-Meier model.

Secondary

Measure	Time frame	Description
Number of Participants With Detectable HCV RNA Due to Re-emergence of Pre-existing Virus Through Week 240	Enrollment up to 240 weeks	—
Number of Participants With Detectable HCV Resistance Mutations Through Week 240	Enrollment up to 240 weeks	—
Number of Participants With Detectable HCV RNA Due to Re-infection Through Week 240	Enrollment up to 240 weeks	Reinfection was defined as HCV RNA \> LLOQ on 2 samples collected at least 1 week apart with a different virus than that present prior to treatment baseline in the parent study.

Countries

Australia, Canada, France, Germany, Italy, New Zealand, Puerto Rico, Spain, United Kingdom, United States

Participant flow

Recruitment details

Participants were enrolled at study sites in Australia, Canada, France, Germany, Italy, New Zealand, Spain, the United Kingdom, and the United States.

Pre-assignment details

1609 participants were enrolled in the registry. 36 participants who were enrolled but did not meet the eligibility criteria (including 19 participants in the 'Enrolled from Ineligible Parent Treatment Group') were not included in the Full Analysis Set and Safety Analysis Set, and thus, are not included in the Baseline Characteristics, Outcome Measures and Serious and Other Adverse Event modules.

Participants by arm

Arm	Count
SOF+RBV Participants who were previously treated with SOF along with RBV were followed up to 5 years.	94
LDV/SOF Participants who were previously treated with SOF/LDV were followed up to 5 years.	275
LDV/SOF+RBV Participants who were previously treated with SOF/LDV along with RBV were followed up to 5 years.	263
SOF/VEL Participants who were previously treated with SOF/VEL were followed up to 5 years.	372
SOF/VEL+RBV Participants who were previously treated with SOF/VEL along with RBV were followed up to 5 years.	98
SOF/VEL/VOX Participants who were previously treated with SOF/VEL/VOX with or without RBV were followed up to 5 years.	332
Other SOF-Based Participants who previously received other SOF based regimen were followed up to 5 years.	139
Total	1,573

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007
Overall Study	Death	3	11	16	22	8	17	3	0
Overall Study	Enrolled but not met eligibility criteria	1	2	2	2	2	6	2	19
Overall Study	Investigator's discretion	4	9	7	11	4	10	1	0
Overall Study	Liver transplant	1	1	11	16	5	6	5	0
Overall Study	Lost to Follow-up	20	44	24	61	21	52	25	0
Overall Study	Missing	0	0	1	1	0	1	0	0
Overall Study	Study terminated by sponsor	0	9	4	21	11	13	3	0
Overall Study	Subject terminated by sponsor	1	0	0	2	1	0	0	0
Overall Study	Virologic relapse or reinfection	1	0	0	1	0	1	0	0
Overall Study	Withdrew consent	15	56	43	36	13	51	20	0

Baseline characteristics

Characteristic	Other SOF-Based	SOF/VEL/VOX	SOF/VEL+RBV	SOF/VEL	LDV/SOF+RBV	LDV/SOF	SOF+RBV	Total
Age, Continuous	59 years STANDARD_DEVIATION 8.1	59 years STANDARD_DEVIATION 7.6	58 years STANDARD_DEVIATION 6.9	58 years STANDARD_DEVIATION 7.3	60 years STANDARD_DEVIATION 7.2	60 years STANDARD_DEVIATION 7.8	56 years STANDARD_DEVIATION 7.4	59 years STANDARD_DEVIATION 7.6
Ethnicity (NIH/OMB) Hispanic or Latino	117 Participants	281 Participants	90 Participants	331 Participants	219 Participants	239 Participants	87 Participants	1364 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants	49 Participants	8 Participants	35 Participants	41 Participants	34 Participants	7 Participants	196 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	0 Participants	6 Participants	3 Participants	2 Participants	0 Participants	13 Participants
Race/Ethnicity, Customized Race American Indian or Alaska Native	1 Participants	1 Participants	0 Participants	4 Participants	2 Participants	0 Participants	1 Participants	9 Participants
Race/Ethnicity, Customized Race Asian	0 Participants	8 Participants	5 Participants	17 Participants	4 Participants	3 Participants	7 Participants	44 Participants
Race/Ethnicity, Customized Race Black	20 Participants	26 Participants	5 Participants	25 Participants	19 Participants	40 Participants	3 Participants	138 Participants
Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	5 Participants
Race/Ethnicity, Customized Race Other	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	3 Participants
Race/Ethnicity, Customized Race Unknown or Not Reported	1 Participants	2 Participants	0 Participants	2 Participants	2 Participants	2 Participants	0 Participants	9 Participants
Race/Ethnicity, Customized Race White	117 Participants	292 Participants	86 Participants	324 Participants	234 Participants	230 Participants	82 Participants	1365 Participants
Region of Enrollment Australia	0 Participants	13 Participants	2 Participants	24 Participants	12 Participants	0 Participants	14 Participants	65 Participants
Region of Enrollment Canada	0 Participants	16 Participants	0 Participants	24 Participants	5 Participants	0 Participants	5 Participants	50 Participants
Region of Enrollment France	0 Participants	24 Participants	0 Participants	20 Participants	32 Participants	46 Participants	0 Participants	122 Participants
Region of Enrollment Germany	0 Participants	12 Participants	0 Participants	7 Participants	3 Participants	3 Participants	1 Participants	26 Participants
Region of Enrollment Italy	0 Participants	0 Participants	0 Participants	10 Participants	13 Participants	2 Participants	1 Participants	26 Participants
Region of Enrollment New Zealand	3 Participants	30 Participants	4 Participants	9 Participants	13 Participants	3 Participants	4 Participants	66 Participants
Region of Enrollment Spain	0 Participants	0 Participants	16 Participants	15 Participants	15 Participants	0 Participants	5 Participants	51 Participants
Region of Enrollment United Kingdom	0 Participants	9 Participants	0 Participants	22 Participants	4 Participants	0 Participants	14 Participants	49 Participants
Region of Enrollment United States	136 Participants	228 Participants	76 Participants	241 Participants	166 Participants	221 Participants	50 Participants	1118 Participants
Sex: Female, Male Female	55 Participants	87 Participants	28 Participants	115 Participants	83 Participants	94 Participants	35 Participants	497 Participants
Sex: Female, Male Male	84 Participants	245 Participants	70 Participants	257 Participants	180 Participants	181 Participants	59 Participants	1076 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	3 / 95	11 / 277	16 / 265	22 / 374	8 / 100	17 / 338	3 / 141	0 / 19
other Total, other adverse events	0 / 94	4 / 275	1 / 263	1 / 372	0 / 98	1 / 332	1 / 139	0 / 0
serious Total, serious adverse events	0 / 94	0 / 275	0 / 263	0 / 372	0 / 98	0 / 332	0 / 139	0 / 0

Outcome results

Primary

Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240

SVR at Week 240 was defined as HCV RNA\< lower limit of quantification (LLOQ i.e., 15 or 25 international units per milliliter \[IU/mL\]) or last available HCV RNA\< LLOQ with no subsequent follow-up values at Week 240 after enrollment in this registry study. Percentage of participants who maintained SVR status by Week 240 was estimated using a Kaplan-Meier model.

Time frame: Week 240

Population: Full Analysis Set included all participants who met all inclusion criteria and did not meet any of the exclusion criteria, and with at least one post-enrollment visit measurement available.

Arm	Measure	Value (NUMBER)
SOF+RBV	Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240	98.9 percentage of participants
LDV/SOF	Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240	100 percentage of participants
LDV/SOF+RBV	Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240	99.6 percentage of participants
SOF/VEL	Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240	99.7 percentage of participants
SOF/VEL+RBV	Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240	100 percentage of participants
SOF/VEL/VOX	Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240	99.6 percentage of participants
Other SOF-Based	Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240	100 percentage of participants

Primary

Percentage of Participants Who Developed Hepatocellular Carcinoma (HCC) Through Week 240

Participants with de novo HCC since registry start were defined as participants who had not been identified with HCC prior to registry start and only had HCC since registry start. The percentage of participants who developed de novo HCC through Week 240 was estimated using a Kaplan-Meier model.