Safety and Efficacy Study of Sofosbuvir Plus Ribavirin in Treatment-Naive Adults With Genotype 1 and 3 Chronic HCV Infection
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT01896193
Collaborator
(none)
127
16
2
12
7.9
0.7
Study Details
Study Description
Brief Summary
This study will evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir plus ribavirin administered for 16 weeks and 24 weeks in participants with chronic genotype 1 (GT1) or genotype 3 (GT3) hepatitis C virus (HCV) infection.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
127 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3b, Multicenter, Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of Sofosbuvir Plus Ribavirin in Treatment-Naïve Adults With Genotype 1 and 3 Chronic HCV Infection.
Study Start Date
:
Jun 1, 2013
Actual Primary Completion Date
:
Apr 1, 2014
Actual Study Completion Date
:
Jun 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SOF+RBV 16 Weeks SOF+RBV for 16 weeks |
Drug: SOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
Other Names:
Drug: RBV
Ribavirin (RBV) tablets administered orally in a divided daily dose using weight-based dosing (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
|
| Experimental: SOF+RBV 24 Weeks SOF+RBV for 24 weeks |
Drug: SOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
Other Names:
Drug: RBV
Ribavirin (RBV) tablets administered orally in a divided daily dose using weight-based dosing (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
|
Outcome Measures
Primary Outcome Measures
- 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.
- Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [Up to 24 weeks]
The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized.
Secondary Outcome Measures
- 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.
- 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)
- Percentage of Participants Experiencing Virologic Relapse [Up to Posttreatment Week 12]
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:
-
Confirmed chronic genotype 1 or 3 HCV infection
-
HCV treatment-naive
-
Individuals will have cirrhosis status assessment; liver biopsy may be required.
-
Screening laboratory values within predefined thresholds
-
Use of two effective contraception methods if female of childbearing potential or sexually active male
Exclusion Criteria:
-
Pregnant or nursing female or male with pregnant female partner
-
Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
-
Contraindication to ribavirin therapy
-
Excessive alcohol ingestion as defined by protocol
-
History of solid organ transplantation
-
Current or prior history of clinical hepatic decompensation
-
History of clinically significant illness or any other medical disorder that may interfere with the individual's treatment, assessment, or compliance with the protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Central Clinical Hospital of the Russian Academy of Sciences | Moscow | Russian Federation | ||
| 2 | Central Scientific and Research Institute of Epidemiology of Rospotrebnadzor | Moscow | Russian Federation | ||
| 3 | Central Scientific Research Institution of Gastroenterology of Moscow Healthcare Department | Moscow | Russian Federation | ||
| 4 | City Clinical Hospital 24 | Moscow | Russian Federation | ||
| 5 | Clinical Diagnostics and Research Center of Federal Bedgetary Institution | Moscow | Russian Federation | ||
| 6 | Infectious Clinical Hospital No. 1 | Moscow | Russian Federation | ||
| 7 | Institute of Nutrition of Academy of Sciences | Moscow | Russian Federation | ||
| 8 | Institution of Healthcare of Sverdlovsk Region | Moscow | Russian Federation | ||
| 9 | Institution of High Professional Education First Moscow State Medical University | Moscow | Russian Federation | ||
| 10 | Institution of Tumen Region | Moscow | Russian Federation | ||
| 11 | Krasnoyarsk Regional Center for Prevention and Control of AIDS and Infectious Diseases | Moscow | Russian Federation | ||
| 12 | Scientific Research Institution of Emergency Care n.a. N.V. Sclifosovskiy of Moscow | Moscow | Russian Federation | ||
| 13 | Stavropol State Medical University of Ministry of Healthcare | Moscow | Russian Federation | ||
| 14 | Medical Military Academy n.a. S.M. Kirov | Saint-Petersburg | Russian Federation | ||
| 15 | Saint-Petersburg Center for Prevention and Control of AIDS and Infectious Diseases | Saint-Petersburg | Russian Federation | ||
| 16 | Medical Company Hepatolog | Samara | Russian Federation |
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:
NCT01896193
Other Study ID Numbers:
- GS-US-334-0119
First Posted:
Jul 11, 2013
Last Update Posted:
May 29, 2015
Last Verified:
May 1, 2015
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at a total of 16 study sites in Russia. The first participant was screened on 06 June 2013. The last study visit occurred on 27 July 2014. |
|---|---|
| Pre-assignment Detail | 139 participants were screened. |
| Arm/Group Title | SOF+RBV 16 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 16 weeks | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks |
| Period Title: Overall Study | ||
| STARTED | 62 | 65 |
| COMPLETED | 41 | 53 |
| NOT COMPLETED | 21 | 12 |
Baseline Characteristics
| Arm/Group Title | SOF+RBV 16 Weeks, GT1 | SOF+RBV 24 Weeks, GT1 | SOF+RBV 16 Weeks, GT3 | SOF+RBV 24 Weeks, GT3 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 3) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 3) | Total of all reporting groups |
| Overall Participants | 32 | 34 | 30 | 31 | 127 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
41
(12.8)
|
42
(9.8)
|
38
(8.2)
|
40
(9.6)
|
40
(10.3)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
19
59.4%
|
18
52.9%
|
11
36.7%
|
12
38.7%
|
60
47.2%
|
| Male |
13
40.6%
|
16
47.1%
|
19
63.3%
|
19
61.3%
|
67
52.8%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||
| White |
32
100%
|
34
100%
|
30
100%
|
31
100%
|
127
100%
|
| Cirrhosis Status (participants) [Number] | |||||
| No |
28
87.5%
|
28
82.4%
|
23
76.7%
|
26
83.9%
|
105
82.7%
|
| Yes |
4
12.5%
|
6
17.6%
|
6
20%
|
5
16.1%
|
21
16.5%
|
| Missing |
0
0%
|
0
0%
|
1
3.3%
|
0
0%
|
1
0.8%
|
| IL28b Status (participants) [Number] | |||||
| CC |
10
31.3%
|
6
17.6%
|
12
40%
|
15
48.4%
|
43
33.9%
|
| CT |
19
59.4%
|
23
67.6%
|
16
53.3%
|
15
48.4%
|
73
57.5%
|
| TT |
3
9.4%
|
5
14.7%
|
2
6.7%
|
1
3.2%
|
11
8.7%
|
| HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [log10 IU/mL] |
6.2
(0.60)
|
6.1
(0.60)
|
6.2
(0.81)
|
6.2
(0.77)
|
6.2
(0.69)
|
| HCV RNA Category (participants) [Number] | |||||
| < 800,000 IU/mL |
12
37.5%
|
11
32.4%
|
10
33.3%
|
10
32.3%
|
43
33.9%
|
| ≥ 800,000 IU/mL |
20
62.5%
|
23
67.6%
|
20
66.7%
|
21
67.7%
|
84
66.1%
|
Outcome Measures
| 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 1 or 3 HCV infection who were randomized and received at least one dose of study drug |
| Arm/Group Title | SOF+RBV 16 Weeks, GT1 | SOF+RBV 24 Weeks, GT1 | SOF+RBV 16 Weeks, GT3 | SOF+RBV 24 Weeks, GT3 |
|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 3) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 3) |
| Measure Participants | 32 | 34 | 30 | 31 |
| Number [percentage of participants] |
50.0
156.3%
|
76.5
225%
|
86.7
289%
|
90.3
291.3%
|
| Title | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) |
|---|---|
| Description | The percentage of participants permanently 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 16 Weeks, GT1 | SOF+RBV 24 Weeks, GT1 | SOF+RBV 16 Weeks, GT3 | SOF+RBV 24 Weeks, GT3 |
|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 3) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 3) |
| Measure Participants | 32 | 34 | 30 | 31 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 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 16 Weeks, GT1 | SOF+RBV 24 Weeks, GT1 | SOF+RBV 16 Weeks, GT3 | SOF+RBV 24 Weeks, GT3 |
|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 3) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 3) |
| Measure Participants | 32 | 34 | 30 | 31 |
| SVR4 |
53.1
165.9%
|
76.5
225%
|
90.0
300%
|
90.3
291.3%
|
| SVR24 |
46.9
146.6%
|
76.5
225%
|
86.7
289%
|
90.3
291.3%
|
| 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 16 Weeks, GT1 | SOF+RBV 24 Weeks, GT1 | SOF+RBV 16 Weeks, GT3 | SOF+RBV 24 Weeks, GT3 |
|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 3) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 3) |
| Measure Participants | 32 | 34 | 30 | 31 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 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 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | SOF+RBV 16 Weeks, GT1 | SOF+RBV 24 Weeks, GT1 | SOF+RBV 16 Weeks, GT3 | SOF+RBV 24 Weeks, GT3 |
|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 1) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 3) | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 3) |
| Measure Participants | 32 | 34 | 30 | 31 |
| Number [percentage of participants] |
50.0
156.3%
|
23.5
69.1%
|
13.3
44.3%
|
9.7
31.3%
|
Adverse Events
| Time Frame | Up to 24 weeks plus 30 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Analysis Set | |||
| Arm/Group Title | SOF+RBV 16 Weeks | SOF+RBV 24 Weeks | ||
| Arm/Group Description | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks | SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks | ||
All Cause Mortality |
||||
| SOF+RBV 16 Weeks | SOF+RBV 24 Weeks | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| SOF+RBV 16 Weeks | SOF+RBV 24 Weeks | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/62 (1.6%) | 1/65 (1.5%) | ||
| Infections and infestations | ||||
| Pneumonia | 1/62 (1.6%) | 0/65 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Foot fracture | 0/62 (0%) | 1/65 (1.5%) | ||
Other (Not Including Serious) Adverse Events |
||||
| SOF+RBV 16 Weeks | SOF+RBV 24 Weeks | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/62 (25.8%) | 21/65 (32.3%) | ||
| General disorders | ||||
| Asthenia | 7/62 (11.3%) | 4/65 (6.2%) | ||
| Fatigue | 2/62 (3.2%) | 4/65 (6.2%) | ||
| Infections and infestations | ||||
| Respiratory tract infection viral | 3/62 (4.8%) | 5/65 (7.7%) | ||
| Nervous system disorders | ||||
| Headache | 5/62 (8.1%) | 10/65 (15.4%) | ||
| Psychiatric disorders | ||||
| Insomnia | 1/62 (1.6%) | 4/65 (6.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 1/62 (1.6%) | 4/65 (6.2%) | ||
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
Results Point of Contact
| Name/Title | Clinical Trial Disclosures |
|---|---|
| Organization | Gilead Sciences |
| Phone | |
| ClinicalTrialDisclosures@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01896193
Other Study ID Numbers:
- GS-US-334-0119
First Posted:
Jul 11, 2013
Last Update Posted:
May 29, 2015
Last Verified:
May 1, 2015