Hepatitis CPhase 2NCT01054729
Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients
A Phase 2 study testing Sofosbuvir, PEG and RBV in people with Hepatitis C, run by Gilead Sciences at 7 sites in 2 countries.
Trial summary
Participants with genotype 1 HCV infection were randomized to 1 of 3 sofosbuvir doses (100 mg, 200 mg, or 400 mg) or matching placebo once daily based upon stratification for IL28B status (CC or CT/TT). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Sofosbuvir, PEG and RBV
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Jan 2010to Aug 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Treatment-naive males and females, 18-65 years of age
- Genotype 1 HCV infection
- Negative pregnancy test for females of childbearing age
- Females of childbearing age and males with female partners of childbearing age must use two forms of contraception during treatment and following the last dose of ribavirin in accordance with locally approved label for ribavirin
Who cannot join
- Hepatitis B or HIV infection
- Pregnant or breast feeding females or male partners of pregnant females
- Previous interferon or ribavirin-based therapy or investigational anti-HCV agent
- History or evidence of medical condition associated with chronic liver disease other than HCV
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Duke University
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32610
Orlando Immunology Center
Orlando, Florida, 32803
Alamo Medical Research Center
San Antonio, Texas, 78215
Quest Clinical Research
San Francisco, California, 94115
Virginia Mason Medical Center
Seattle, Washington, 98101
Puerto Rico1 site
Fundacion de Investigacion de Diego
Santurce, Puerto Rico, 00909
About this study
Official title: A Multi-center, Double-Blind, Parallel Group, Randomized, Placebo-Controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Standard of Care (Pegylated Interferon and Ribavirin) in Treatment-Naïve Patients With Chronic HCV Infection Genotype 1
Participants with genotype 1 HCV infection were randomized to 1 of 3 sofosbuvir doses (100 mg, 200 mg, or 400 mg) or matching placebo once daily based upon stratification for IL28B status (CC or CT/TT). Placebo tablets were administered to participants receiving 100 mg active sofosbuvir (3 placebo tablets) and 200 mg active sofosbuvir (2 placebo tablets) in order to maintain the study blind. Participants received sofosbuvir/matching placebo from Day 0 to 27. Participants also received treatment with PEG+RBV starting on Day 0 of the study which continued for 48 weeks. Participants were evaluated for sustained virologic response (SVR) for an additional 24 weeks following completion of study treatment.
- Conditions
- Hepatitis C
- Being tested
- Sofosbuvir, Placebo, PEG, RBV
- Keywords
- Chronic Hepatitis C infection Genotype 1, HCV, GT1, GT 1
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SofosbuvirDrug
Also called Sovaldi®, GS-7977, PSI-7977
Sofosbuvir tablet(s) administered orally once daily
PlaceboDrug
Placebo to match sofosbuvir administered orally once daily
PEGDrug
Also called Pegasys®
Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.
RBVDrug
Also called Copegus®
Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).
| Study group | Role | What they receive |
|---|---|---|
| Sofosbuvir 100 mg+PEG+RBV | Experimental | Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Receives: Drug: Sofosbuvir; Drug: PEG; Drug: RBV |
| Sofosbuvir 200 mg+PEG+RBV | Experimental | Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Receives: Drug: Sofosbuvir; Drug: PEG; Drug: RBV |
| Sofosbuvir 400 mg+PEG+RBV | Experimental | Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Receives: Drug: Sofosbuvir; Drug: PEG; Drug: RBV |
| Placebo+PEG+RBV | Active comparator | Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) Receives: Drug: Placebo; Drug: PEG; Drug: RBV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period
Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.
Measured: Baseline to Week 4
Secondary outcomes (16)
Change in Circulating HCV RNA at Week 4
Measured: Baseline to Week 4
Percentage of Participants With Rapid Virologic Response at Week 4
Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD [15 IU/mL]) at Week 4.
Measured: Week 4
Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment
SVR at 12 weeks (SVR12) and 24 weeks (SVR24) was defined as HCV RNA < LOD 12 and 24 weeks after last dose of PEG+RBV, respectively, following completion of 48 weeks of treatment (4 weeks of sofosbuvir or matching placebo and PEG+RBV, followed by an additional 44 weeks of PEG+RBV).
Measured: Post-treatment Weeks 12 and 24
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0
The Cmax of sofosbuvir was measured at Day 0 following a single dose of sofosbuvir.
Cmax is defined as the maximum concentration of drug.
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27
The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0
The AUCinf of sofosbuvir was analyzed at Day 0 (following a single dose of sofosbuvir).
AUCinf is defined as the concentration of drug (area under the plasma concentration versus time curve) extrapolated to infinite time.
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27
The AUCtau of sofosbuvir was analyzed at Day 27 (following continuous dosing of sofosbuvir).
AUCtau is defined as the concentration of drug (area under the plasma concentration versus time curve) over the dosing interval.
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-331007: Cmax at Day 0
The Cmax of GS-331007 was measured at Day 0 following a single dose of sofosbuvir. GS-331007 is the predominant circulating metabolite of sofosbuvir.
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-331007: Cmax at Day 27
The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0
The AUCinf of GS-331007 was analyzed at Day 0 (following a single dose of sofosbuvir).
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27
The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-566500: Cmax at Day 0
The Cmax of GS-566500 was measured at Day 0 following a single dose of sofosbuvir. GS-566500 is one of the major metabolites of sofosbuvir.
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-566500: Cmax at Day 27
The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0
The AUCinf of GS-566500 was analyzed at Day 0 (following a single dose of sofosbuvir).
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27
The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Measured: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Percentage of Participants Who Developed Resistance to Sofosbuvir
Measured: Baseline to Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2010 (estimated)
- Study startJan 2010
- Primary completionApr 2010
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert H. Hyland, DPhil, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01054729
- Sponsor's protocol ID
- P7977-0221
- Status last verified
- Mar 2014
- First submitted
- 21 Jan 2010
- Last updated
- 17 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Double-Blind, Parallel Group, Randomized, Placebo-Controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Standard of Care (Pegylated Interferon and Ribavirin) in Treatment-Naïve Patients With Chronic HCV Infection Genotype 1
- ClinicalTrials.gov ID
- NCT01054729
- Acronym / sponsor ID
- P7977-0221
- Conditions
- Hepatitis C
- Keywords
- Chronic Hepatitis C infection Genotype 1, HCV, GT1, GT 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Jan 2010
- Primary completion
- Apr 2010 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 22 Jan 2010 (estimated)
- Results
- Posted 19 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Participants with genotype 1 HCV infection were randomized to 1 of 3 sofosbuvir doses (100 mg, 200 mg, or 400 mg) or matching placebo once daily based upon stratification for IL28B status (CC or CT/TT). Placebo tablets were administered to participants receiving 100 mg active sofosbuvir (3 placebo tablets) and 200 mg active sofosbuvir (2 placebo tablets) in order to maintain the study blind. Participants received sofosbuvir/matching placebo from Day 0 to 27. Participants also received treatment with PEG+RBV starting on Day 0 of the study which continued for 48 weeks. Participants were evaluated for sustained virologic response (SVR) for an additional 24 weeks following completion of study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sofosbuvir 100 mg+PEG+RBV | Experimental | Drug: Sofosbuvir, Drug: PEG, Drug: RBVParticipants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) |
| Sofosbuvir 200 mg+PEG+RBV | Experimental | Drug: Sofosbuvir, Drug: PEG, Drug: RBVParticipants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) |
| Sofosbuvir 400 mg+PEG+RBV | Experimental | Drug: Sofosbuvir, Drug: PEG, Drug: RBVParticipants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) |
| Placebo+PEG+RBV | Active comparator | Drug: Placebo, Drug: PEG, Drug: RBVParticipants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Treatment-naive males and females, 18-65 years of age
- Genotype 1 HCV infection
- Negative pregnancy test for females of childbearing age
- Females of childbearing age and males with female partners of childbearing age must use two forms of contraception during treatment and following the last dose of ribavirin in accordance with locally approved label for ribavirin
Key exclusion criteria (4 listed)
- Hepatitis B or HIV infection
- Pregnant or breast feeding females or male partners of pregnant females
- Previous interferon or ribavirin-based therapy or investigational anti-HCV agent
- History or evidence of medical condition associated with chronic liver disease other than HCV
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SofosbuvirAlso: Sovaldi®, GS-7977, PSI-7977Sofosbuvir tablet(s) administered orally once daily | Drug | Sofosbuvir 100 mg+PEG+RBV, Sofosbuvir 200 mg+PEG+RBV, Sofosbuvir 400 mg+PEG+RBV |
| PlaceboPlacebo to match sofosbuvir administered orally once daily | Drug | Placebo+PEG+RBV |
| PEGAlso: Pegasys®Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection. | Drug | Placebo+PEG+RBV, Sofosbuvir 100 mg+PEG+RBV, Sofosbuvir 200 mg+PEG+RBV, Sofosbuvir 400 mg+PEG+RBV |
| RBVAlso: Copegus®Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg). | Drug | Placebo+PEG+RBV, Sofosbuvir 100 mg+PEG+RBV, Sofosbuvir 200 mg+PEG+RBV, Sofosbuvir 400 mg+PEG+RBV |
Primary outcome
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period
Time frame: Baseline to Week 4
Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.
16 secondary outcomes
Change in Circulating HCV RNA at Week 4
Time frame: Baseline to Week 4
Percentage of Participants With Rapid Virologic Response at Week 4
Time frame: Week 4
Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment
Time frame: Post-treatment Weeks 12 and 24
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-331007: Cmax at Day 0
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-331007: Cmax at Day 27
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-566500: Cmax at Day 0
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-566500: Cmax at Day 27
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose
Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27
Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)
Percentage of Participants Who Developed Resistance to Sofosbuvir
Time frame: Baseline to Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert H. Hyland, DPhil study director
Gilead Sciences
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sofosbuvir, PEG and RBV in people with Hepatitis C, run by Gilead Sciences at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period (time frame: Baseline to Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2014.