Sofosbuvir Plus Ribavirin Administered for Either 12 or 24 Weeks 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: NCT01838590
• Collaborator: (none)
• Enrollment: 103
• Locations: 2
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 51.5
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus	Drug: SOF; Drug: RBV	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of Sofosbuvir Plus Ribavirin Administered for Either 12 or 24 Weeks in Treatment-Naïve and Treatment-Experienced Egyptian Adults With Chronic Genotype 4 HCV Infection.
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SOF+RBV 12 Weeks Participants will receive SOF+RBV for 12 weeks.	Drug: SOF; Sofosbuvir (SOF) 400 mg tablet administered orally once daily; Other Names: Sovaldi® GS-7977 ; Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: SOF+RBV 24 Weeks Participants will receive SOF+RBV for 24 weeks.	Drug: SOF; Sofosbuvir (SOF) 400 mg tablet administered orally once daily; Other Names: Sovaldi® GS-7977 ; Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose (< 75 kg = 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. Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [Up to 24 weeks]

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 SVR 24 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 Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)

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

   Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Treatment experienced and naïve subjects

• Chronic genotype 4 HCV-infection

• Not co-infected with HIV

• Screening laboratory values within defined thresholds

• Use of highly effective contraception methods

• Subject 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 subject 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		Cairo		Egypt
2		Mansoura		Egypt

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Kathryn Kersey, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01838590
• Other Study ID Numbers: GS-US-334-0138
• First Posted: Apr 24, 2013
• Last Update Posted: May 22, 2015
• Last Verified: May 1, 2015

• Keywords provided by Gilead Sciences: Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Flaviviridae Infections; Antiviral Agents; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Antimetabolites; Molecular Mechanisms of Pharmacological Action; HCV genotype 4 (GT-4); HCV; Sustained Virologic Response; Direct Acting Antiviral; Combination Therapy; GS-7977; Ribavirin; Open Label; Sofosbuvir; Additional relevant MeSH terms:; Hepatitis; Hepatitis, Chronic; Hepatitis C; Hepatitis C, Chronic
• Additional relevant MeSH terms: Infections; Hepatitis A; Hepatitis C; Hepatitis; Sofosbuvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a total of 3 study sites in Egypt. The first participant was screened on 30 March 2013. The last study visit occurred on 04 August 2014.
Pre-assignment Detail	141 participants were screened.

Arm/Group Title	SOF+RBV 12 Weeks	SOF+RBV 24 Weeks
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	52	51
COMPLETED	40	46
NOT COMPLETED	12	5

Baseline Characteristics

Arm/Group Title	SOF+RBV 12 Weeks, TN	SOF+RBV 12 Weeks, TE	SOF+RBV 24 Weeks, TN	SOF+RBV 24 Weeks, 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	25	27	24	27	103
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43 (12.3)	46 (11.5)	46 (14.5)	51 (8.3)	47 (11.9)
Sex: Female, Male (Count of Participants)
Female	7 28%	8 29.6%	11 45.8%	8 29.6%	34 33%
Male	18 72%	19 70.4%	13 54.2%	19 70.4%	69 67%
Race/Ethnicity, Customized (participants) [Number]
White	25 100%	27 100%	24 100%	27 100%	103 100%
Race/Ethnicity, Customized (participants) [Number]
Not Hispanic or Latino	25 100%	27 100%	24 100%	27 100%	103 100%
Cirrhosis Status (participants) [Number]
No	22 88%	22 81.5%	21 87.5%	21 77.8%	86 83.5%
Yes	3 12%	5 18.5%	3 12.5%	6 22.2%	17 16.5%
IL28b Status (participants) [Number]
CC	8 32%	1 3.7%	6 25%	5 18.5%	20 19.4%
CT	12 48%	18 66.7%	12 50%	21 77.8%	63 61.2%
TT	5 20%	8 29.6%	6 25%	1 3.7%	20 19.4%
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	5.6 (0.73)	5.9 (0.57)	5.5 (0.75)	6.2 (0.49)	5.8 (0.70)
HCV RNA Category (participants) [Number]
< 800,000 IU/mL	15 60%	11 40.7%	15 62.5%	8 29.6%	49 47.6%
≥ 800,000 IU/mL	10 40%	16 59.3%	9 37.5%	19 70.4%	54 52.4%

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 and received at least one dose of study drug

Arm/Group Title	SOF+RBV 12 Weeks, TN	SOF+RBV 12 Weeks, TE	SOF+RBV 24 Weeks, TN	SOF+RBV 24 Weeks, 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	25	27	24	27
Number [percentage of participants]	84.0 336%	70.4 260.7%	91.7 382.1%	88.9 329.3%

2. Primary Outcome

Title	Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
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 Weeks	SOF+RBV 24 Weeks
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	52	51
Number [percentage of participants]	0 0%	0 0%

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 SVR 24 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 Weeks, TN	SOF+RBV 12 Weeks, TE	SOF+RBV 24 Weeks, TN	SOF+RBV 24 Weeks, 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	25	27	24	27
SVR4	88.0 352%	74.1 274.4%	91.7 382.1%	88.9 329.3%
SVR24	84.0 336%	70.4 260.7%	91.7 382.1%	88.9 329.3%

4. Secondary Outcome

Title	Percentage of Participants Experiencing On-treatment Virologic Failure
Description	On-treatment virologic failure was defined as Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (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 Weeks, TN	SOF+RBV 12 Weeks, TE	SOF+RBV 24 Weeks, TN	SOF+RBV 24 Weeks, 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	25	27	24	27
Number [percentage of participants]	0 0%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Percentage of Participants Experiencing Virologic Relapse
Description	Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
Time Frame	Up to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF+RBV 12 Weeks, TN	SOF+RBV 12 Weeks, TE	SOF+RBV 24 Weeks, TN	SOF+RBV 24 Weeks, 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	25	27	24	27
Number [percentage of participants]	16.0 64%	29.6 109.6%	4.2 17.5%	11.1 41.1%

Adverse Events

Time Frame	Up to 24 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set
Arm/Group Title	SOF+RBV 12 Weeks		SOF+RBV 24 Weeks
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 Weeks		SOF+RBV 24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	SOF+RBV 12 Weeks		SOF+RBV 24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		2/51 (3.9%)
Nervous system disorders
Cerebral Ischaemia	0/52 (0%)		1/51 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/52 (0%)		1/51 (2%)
Other (Not Including Serious) Adverse Events
	SOF+RBV 12 Weeks		SOF+RBV 24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/52 (65.4%)		38/51 (74.5%)
Blood and lymphatic system disorders
Anaemia	6/52 (11.5%)		10/51 (19.6%)
Gastrointestinal disorders
Dyspepsia	4/52 (7.7%)		8/51 (15.7%)
Abdominal pain upper	6/52 (11.5%)		3/51 (5.9%)
Gastrooesophageal reflux disease	2/52 (3.8%)		5/51 (9.8%)
Abdominal pain	2/52 (3.8%)		3/51 (5.9%)
Diarrhoea	1/52 (1.9%)		4/51 (7.8%)
Nausea	1/52 (1.9%)		4/51 (7.8%)
Constipation	4/52 (7.7%)		0/51 (0%)
Vomiting	1/52 (1.9%)		3/51 (5.9%)
General disorders
Fatigue	7/52 (13.5%)		14/51 (27.5%)
Pyrexia	2/52 (3.8%)		3/51 (5.9%)
Infections and infestations
Nasopharyngitis	1/52 (1.9%)		3/51 (5.9%)
Musculoskeletal and connective tissue disorders
Bone pain	4/52 (7.7%)		4/51 (7.8%)
Back pain	1/52 (1.9%)		3/51 (5.9%)
Muscle spasms	1/52 (1.9%)		3/51 (5.9%)
Arthralgia	0/52 (0%)		3/51 (5.9%)
Nervous system disorders
Headache	6/52 (11.5%)		11/51 (21.6%)
Somnolence	2/52 (3.8%)		3/51 (5.9%)
Psychiatric disorders
Insomnia	7/52 (13.5%)		10/51 (19.6%)
Renal and urinary disorders
Renal colic	0/52 (0%)		3/51 (5.9%)
Respiratory, thoracic and mediastinal disorders
Cough	4/52 (7.7%)		5/51 (9.8%)
Oropharyngeal pain	3/52 (5.8%)		6/51 (11.8%)
Dyspnoea	1/52 (1.9%)		3/51 (5.9%)
Skin and subcutaneous tissue disorders
Pruritus	2/52 (3.8%)		9/51 (17.6%)

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