Sofosbuvir (GS-7977) in Combination With PEG and Ribavirin for 12 Weeks in Treatment Experienced Subjects With Chronic HCV Infection Genotype 2 or 3

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01808248
• Collaborator: (none)
• Enrollment: 47
• Location: 1
• Arm: 1
• Duration (Months): 10
• Patients Per Site Per Month: 4.7

Study Details

Study Description

Brief Summary

This study is to evaluate the safety, tolerability, and antiviral efficacy of sofosbuvir (SOF) in combination with peginterferon alfa 2a (PEG) and ribavirin (RBV) administered for 12 weeks in participants with chronic genotype 2 or 3 hepatitis C virus (HCV) infection who have previously failed prior treatment with an interferon-based regimen.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: SOF; Drug: PEG; Drug: RBV	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label Study of Sofosbuvir in Combination With PEG and Ribavirin for 12 Weeks in Treatment Experienced Subjects With Chronic HCV Infection Genotype 2 or 3
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SOF+PEG+RBV Participants will receive SOF+PEG+RBV for 12 weeks.	Drug: SOF; Sofosbuvir (SOF) 400 mg tablet administered orally once daily; Other Names: Sovaldi® GS-7977 PSI-7977 ; Drug: PEG; Peginterferon alfa 2a (PEG) 180 μg administered once weekly by subcutaneous injection; Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) [Posttreatment Week 12]

   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 15 IU/mL) at 12 weeks after stopping study treatment.

2. Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [Up to 12 weeks]

   The percentage of participants discontinuing any study drug due to an adverse event was summarized.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [Posttreatment Weeks 4 and 24]

   SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.

2. Percentage of Participants Experiencing On-treatment Virologic Failure [Up to 12 weeks]

   On-treatment virologic failure was defined as: Viral breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or Viral rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment

3. Percentage of Participants Experiencing Viral Relapse [Up to Posttreatment Week 24]

   Viral relapse was defined as having HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at the end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Infection with genotype 2 or 3 HCV infection

• Cirrhosis determination

• Individual is treatment-experienced

• Screening laboratory values within defined thresholds

• Individual has not been treated with any investigational drug or device within 30 days of the Screening visit

• Use of highly effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

• Prior exposure to a direct-acting antiviral drug targeting the HCV NS5B polymerase

• Pregnant or nursing female or male with pregnant female partner

• Current or prior history of clinical hepatic decompensation

• History of clinically-significant illness or any other major medical disorder that may interfere with treatment, assessment, or compliance with the study protocol

• Excessive alcohol ingestion or significant drug abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alamo Medical Research	San Antonio	Texas	United States	78215

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Rob Hyland, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Medicine Plus
• Hepatitis
• Hepatitis A
• Hepatitis C
• Drug Information available for:
• Ribavirin
• PEGINTERFERON ALFA-2A
• U.S. FDA Resources

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01808248
• Other Study ID Numbers: GS-US-334-0151
• First Posted: Mar 11, 2013
• Last Update Posted: Sep 12, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Gilead Sciences: HCV genotype 2 (GT-2); HCV genotype 3 (GT-3); HCV; Sustained Virologic Response; Direct Acting Antiviral; Combination Therapy; Treatment-Naïve; GS-7977; Ribavirin; RBV; Peginterferon Alfa 2a; PEG; Additional relevant MeSH terms:; Hepatitis; Hepatitis A; Hepatitis, Chronic; Hepatitis C; Hepatitis C, Chronic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Flaviviridae Infections; Peginterferon alfa-2a; Interferon-alpha; Antiviral Agents; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Physiological Effects of Drugs
• Additional relevant MeSH terms: Infections; Hepatitis C; Hepatitis; Sofosbuvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a single site in the United States. The first participant was screened on 18 February 2013. The last participant observation occurred on 06 December 2013.
Pre-assignment Detail	56 participants were screened; 47 participants were enrolled and treated, and comprise the Safety Analysis Set and the Full Analysis Set.

Arm/Group Title	SOF+PEG+RBV
Arm/Group Description	Sofosbuvir (SOF) 400 mg tablet once daily + peginterferon alfa 2a (PEG) 180 μg subcutaneous injection once weekly + weight-based ribavirin (RBV; 1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks.
Period Title: Overall Study
STARTED	47
Completed Posttreatment Week 12 Visit	45
COMPLETED	42
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Genotype 2	Genotype 3	Total
Arm/Group Description	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 hepatitis C virus (HCV) infection.	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.	Total of all reporting groups
Overall Participants	23	24	47
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (6.1)	54 (6.9)	56 (6.9)
Sex: Female, Male (Count of Participants)
Female	9 39.1%	6 25%	15 31.9%
Male	14 60.9%	18 75%	32 68.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 47.8%	10 41.7%	21 44.7%
Not Hispanic or Latino	12 52.2%	14 58.3%	26 55.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	0 0%	1 4.2%	1 2.1%
White	22 95.7%	23 95.8%	45 95.7%
Asian	1 4.3%	0 0%	1 2.1%
Liver Cirrhosis (participants) [Number]
No	9 39.1%	12 50%	21 44.7%
Yes	14 60.9%	12 50%	26 55.3%
IL28b Status (participants) [Number]
CC	10 43.5%	7 29.2%	17 36.2%
CT	10 43.5%	15 62.5%	25 53.2%
TT	3 13%	2 8.3%	5 10.6%
HCV RNA (log10 IU/mL) (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.4 (0.66)	6.0 (0.62)	6.2 (0.66)
HCV RNA Category (participants) [Number]
< 6 log10 IU/mL	4 17.4%	13 54.2%	17 36.2%
≥ 6 log10 IU/mL	19 82.6%	11 45.8%	30 63.8%
Response to prior HCV treatment (participants) [Number]
Nonresponse	2 8.7%	5 20.8%	7 14.9%
Relapse/Breakthrough	21 91.3%	19 79.2%	40 85.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 15 IU/mL) at 12 weeks after stopping study treatment.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants with genotype 2 or 3 HCV infection who were enrolled and received at least 1 dose of study drug

Arm/Group Title	Genotype 2	Genotype 3
Arm/Group Description	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
Measure Participants	23	24
Number [percentage of participants]	95.7 416.1%	83.3 347.1%

2. Primary Outcome

Title	Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
Description	The percentage of participants discontinuing any study drug due to an adverse event was summarized.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants enrolled and received at least 1 dose of study drug

Arm/Group Title	SOF+PEG+RBV
Arm/Group Description	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks.
Measure Participants	47
Number [percentage of participants]	8.5 37%

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description	SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Time Frame	Posttreatment Weeks 4 and 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Genotype 2	Genotype 3
Arm/Group Description	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
Measure Participants	23	24
SVR4	95.7 416.1%	87.5 364.6%
SVR24	95.7 416.1%	83.3 347.1%

4. Secondary Outcome

Title	Percentage of Participants Experiencing On-treatment Virologic Failure
Description	On-treatment virologic failure was defined as: Viral breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or Viral rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Genotype 2	Genotype 3
Arm/Group Description	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
Measure Participants	23	24
Number [percentage of participants]	0 0%	0 0%

5. Secondary Outcome

Title	Percentage of Participants Experiencing Viral Relapse
Description	Viral relapse was defined as having HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at the end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.
Time Frame	Up to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	Genotype 2	Genotype 3
Arm/Group Description	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
Measure Participants	22	23
Number [percentage of participants]	0 0%	8.7 36.3%

Adverse Events

Time Frame	Up to 12 weeks plus 30 days
Arm/Group Title	SOF+PEG+RBV
Arm/Group Description	SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks.
All Cause Mortality
	SOF+PEG+RBV
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SOF+PEG+RBV
	Affected / at Risk (%)	# Events
Total	4/47 (8.5%)
Blood and lymphatic system disorders
Anaemia	1/47 (2.1%)
Gastrointestinal disorders
Oesophageal varices haemorrhage	1/47 (2.1%)
Hepatobiliary disorders
Cholecystitis	1/47 (2.1%)
Hepatic cirrhosis	1/47 (2.1%)
Infections and infestations
Sepsis	1/47 (2.1%)
Other (Not Including Serious) Adverse Events
	SOF+PEG+RBV
	Affected / at Risk (%)	# Events
Total	45/47 (95.7%)
Blood and lymphatic system disorders
Anaemia	14/47 (29.8%)
Neutropenia	11/47 (23.4%)
Thrombocytopenia	7/47 (14.9%)
Gastrointestinal disorders
Nausea	8/47 (17%)
Diarrhoea	5/47 (10.6%)
Aphthous stomatitis	3/47 (6.4%)
General disorders
Influenza like illness	26/47 (55.3%)
Fatigue	15/47 (31.9%)
Infections and infestations
Upper respiratory tract infection	4/47 (8.5%)
Sinusitis	3/47 (6.4%)
Metabolism and nutrition disorders
Decreased appetitie	4/47 (8.5%)
Musculoskeletal and connective tissue disorders
Myalgia	3/47 (6.4%)
Nervous system disorders
Headache	7/47 (14.9%)
Dizziness	4/47 (8.5%)
Psychiatric disorders
Insomnia	6/47 (12.8%)
Respiratory, thoracic and mediastinal disorders
Cough	4/47 (8.5%)
Skin and subcutaneous tissue disorders
Rash	7/47 (14.9%)
Pruritis	3/47 (6.4%)
Vascular disorders
Hypertension	5/47 (10.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years