Sofosbuvir Plus Ribavirin in Treatment-Naive and Treatment-Experienced Egyptian Adults With Chronic Genotype 4 Hepatitis C Virus (HCV) Infection

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01713283
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

This study is to evaluate the safety, tolerability, and antiviral activity of sofosbuvir (SOF) with ribavirin (RBV) in Egyptian adults with chronic genotype 4 hepatitis C virus (HCV) infection.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Sofosbuvir Plus Ribavirin Administered for Either 12 or 24 Weeks in Treatment-Naive and Treatment-Experienced Egyptian Adults With Chronic Genotype 4 HCV Infection
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SOF+RBV 12 Weeks Treatment-naive and treatment-experienced participants will receive SOF+RBV for 12 weeks.	Drug: SOF; Sofosbuvir (SOF) 400 mg tablet administered orally once daily; Other Names: GS-7977 PSI-7977 Sovaldi® ; 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)
Experimental: SOF+RBV 24 Weeks Treatment-naive and treatment-experienced participants will receive SOF+RBV for 24 weeks.	Drug: SOF; Sofosbuvir (SOF) 400 mg tablet administered orally once daily; Other Names: GS-7977 PSI-7977 Sovaldi® ; 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, 25 IU/mL) at 12 weeks after stopping study treatment.

2. Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [Up to 24 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 24 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 achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• First generation Egyptian; must have been born in Egypt and can trace both maternal and paternal Egyptian ancestry

• Treatment-experienced or treatment-naive

• Chronic genotype 4 HCV infection

• Not co-infected with HIV

• Screening laboratory values within defined thresholds

• Use of highly effective contraception methods

• Must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments

Exclusion Criteria:

• History of any other clinically significant chronic liver disease

• Pregnant or nursing female or male with pregnant female partner

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

• Excessive alcohol ingestion or significant drug abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Kathryn Kersey, MSc, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01713283
• Other Study ID Numbers: GS-US-334-0114
• First Posted: Oct 24, 2012
• Last Update Posted: Nov 25, 2014
• Last Verified: Nov 1, 2014

• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Sofosbuvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at one study site in the United States. The first participant was screened on 01 October 2012. The last participant observation occurred on 12 February 2014.
Pre-assignment Detail	76 participants were screened.

Arm/Group Title	SOF+RBV 12 Wk	SOF+RBV 24 Wk
Arm/Group Description	Sofosbuvir (SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000-1200 mg daily based on weight) for 12 weeks	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Period Title: Overall Study
STARTED	31	29
COMPLETED	20	26
NOT COMPLETED	11	3

Baseline Characteristics

Arm/Group Title	SOF+RBV 12 Wk TN	SOF+RBV 12 Wk TE	SOF+RBV 24 Wk TN	SOF+RBV 24 Wk TE	Total
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment naive (TN))	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment experienced (TE))	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment experienced)	Total of all reporting groups
Overall Participants	14	17	14	15	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (12.4)	54 (11.5)	52 (15.6)	57 (9.9)	54 (12.2)
Sex: Female, Male (Count of Participants)
Female	6 42.9%	3 17.6%	9 64.3%	1 6.7%	19 31.7%
Male	8 57.1%	14 82.4%	5 35.7%	14 93.3%	41 68.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	14 100%	17 100%	14 100%	15 100%	60 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	14 100%	17 100%	14 100%	15 100%	60 100%
Liver Cirrhosis (participants) [Number]
No	11 78.6%	13 76.5%	11 78.6%	11 73.3%	46 76.7%
Yes	3 21.4%	4 23.5%	3 21.4%	4 26.7%	14 23.3%
IL28b Status (participants) [Number]
CC	3 21.4%	1 5.9%	6 42.9%	0 0%	10 16.7%
CT	9 64.3%	11 64.7%	7 50%	12 80%	39 65%
TT	2 14.3%	5 29.4%	1 7.1%	3 20%	11 18.3%
HCV RNA (log10 IU/mL) (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	5.7 (0.59)	6.2 (0.58)	5.9 (0.74)	6.1 (0.45)	6.0 (0.61)
HCV RNA Category (participants) [Number]
< 800,000 IU/mL	7 50%	4 23.5%	8 57.1%	7 46.7%	26 43.3%
≥ 800,000 IU/mL	7 50%	13 76.5%	6 42.9%	8 53.3%	34 56.7%

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, 25 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 4 HCV infection who were randomized into the study and received at least 1 dose of study drug

Arm/Group Title	SOF+RBV 12 Wk TN	SOF+RBV 12 Wk TE	SOF+RBV 24 Wk TN	SOF+RBV 24 Wk TE
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment experienced)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment experienced)
Measure Participants	14	17	14	15
Number [percentage of participants]	78.6 561.4%	58.8 345.9%	100.0 714.3%	86.7 578%

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 24 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug

Arm/Group Title	SOF+RBV 12 Wk	SOF+RBV 24 Wk
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	31	29
Number [percentage of participants]	0 0%	3.4 20%

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	SOF+RBV 12 Wk TN	SOF+RBV 12 Wk TE	SOF+RBV 24 Wk TN	SOF+RBV 24 Wk TE
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment experienced)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment experienced)
Measure Participants	14	17	14	15
SVR4	78.6 561.4%	58.8 345.9%	100.0 714.3%	93.3 622%
SVR24	78.6 561.4%	58.8 345.9%	100.0 714.3%	86.7 578%

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 24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF+RBV 12 Wk TN	SOF+RBV 12 Wk TE	SOF+RBV 24 Wk TN	SOF+RBV 24 Wk TE
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment experienced)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment experienced)
Measure Participants	14	17	14	15
Number [percentage of participants]	7.1 50.7%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Percentage of Participants Experiencing Viral Relapse
Description	Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.
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	SOF+RBV 12 Wk TN	SOF+RBV 12 Wk TE	SOF+RBV 24 Wk TN	SOF+RBV 24 Wk TE
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment experienced)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment experienced)
Measure Participants	13	17	14	15
Number [percentage of participants]	15.4 110%	41.2 242.4%	0 0%	13.3 88.7%

Adverse Events

Time Frame	Up to 24 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set
Arm/Group Title	SOF+RBV 12 Wk		SOF+RBV 24 Wk
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks		SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
All Cause Mortality
	SOF+RBV 12 Wk		SOF+RBV 24 Wk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	SOF+RBV 12 Wk		SOF+RBV 24 Wk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		3/29 (10.3%)
Gastrointestinal disorders
Abdominal pain	0/31 (0%)		1/29 (3.4%)
General disorders
Non-cardiac chest pain	0/31 (0%)		1/29 (3.4%)
Nervous system disorders
Loss of consciousness	0/31 (0%)		1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	SOF+RBV 12 Wk		SOF+RBV 24 Wk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/31 (90.3%)		29/29 (100%)
Blood and lymphatic system disorders
Anaemia	0/31 (0%)		3/29 (10.3%)
Cardiac disorders
Palpitations	2/31 (6.5%)		6/29 (20.7%)
Ear and labyrinth disorders
Tinnitus	0/31 (0%)		2/29 (6.9%)
Gastrointestinal disorders
Abdominal distension	4/31 (12.9%)		6/29 (20.7%)
Nausea	2/31 (6.5%)		6/29 (20.7%)
Diarrhoea	1/31 (3.2%)		6/29 (20.7%)
Abdominal pain	2/31 (6.5%)		4/29 (13.8%)
Abdominal pain upper	3/31 (9.7%)		3/29 (10.3%)
Dyspepsia	2/31 (6.5%)		4/29 (13.8%)
Vomiting	1/31 (3.2%)		4/29 (13.8%)
Constipation	1/31 (3.2%)		2/29 (6.9%)
Dry mouth	0/31 (0%)		2/29 (6.9%)
Fatigue	14/31 (45.2%)		15/29 (51.7%)
Irritability	6/31 (19.4%)		10/29 (34.5%)
Pain	4/31 (12.9%)		6/29 (20.7%)
Pyrexia	1/31 (3.2%)		5/29 (17.2%)
Malaise	0/31 (0%)		2/29 (6.9%)
Infections and infestations
Bronchitis	0/31 (0%)		4/29 (13.8%)
Nasopharyngitis	0/31 (0%)		2/29 (6.9%)
Urinary tract infection	0/31 (0%)		2/29 (6.9%)
Metabolism and nutrition disorders
Decreased appetite	3/31 (9.7%)		2/29 (6.9%)
Hypokalaemia	2/31 (6.5%)		1/29 (3.4%)
Musculoskeletal and connective tissue disorders
Myalgia	2/31 (6.5%)		6/29 (20.7%)
Back pain	2/31 (6.5%)		5/29 (17.2%)
Pain in extremity	1/31 (3.2%)		5/29 (17.2%)
Arthralgia	1/31 (3.2%)		2/29 (6.9%)
Flank pain	0/31 (0%)		3/29 (10.3%)
Musculoskeletal pain	2/31 (6.5%)		1/29 (3.4%)
Nervous system disorders
Headache	18/31 (58.1%)		19/29 (65.5%)
Dizziness	5/31 (16.1%)		9/29 (31%)
Memory impairment	2/31 (6.5%)		3/29 (10.3%)
Disturbance in attention	0/31 (0%)		2/29 (6.9%)
Hypersomnia	0/31 (0%)		2/29 (6.9%)
Psychiatric disorders
Insomnia	16/31 (51.6%)		14/29 (48.3%)
Depression	3/31 (9.7%)		2/29 (6.9%)
Anxiety	2/31 (6.5%)		1/29 (3.4%)
Renal and urinary disorders
Pollakiuria	0/31 (0%)		4/29 (13.8%)
Dysuria	0/31 (0%)		2/29 (6.9%)
Nephrolithiasis	0/31 (0%)		2/29 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough	6/31 (19.4%)		13/29 (44.8%)
Oropharyngeal pain	5/31 (16.1%)		8/29 (27.6%)
Dyspnoea	5/31 (16.1%)		7/29 (24.1%)
Rhinorrhoea	3/31 (9.7%)		5/29 (17.2%)
Dyspnoea exertional	0/31 (0%)		2/29 (6.9%)
Epistaxis	0/31 (0%)		2/29 (6.9%)
Skin and subcutaneous tissue disorders
Pruritus	7/31 (22.6%)		7/29 (24.1%)
Rash	1/31 (3.2%)		9/29 (31%)
Skin hyperpigmentation	1/31 (3.2%)		2/29 (6.9%)
Dry skin	0/31 (0%)		2/29 (6.9%)

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