Chronic Hepatitis C VirusPhase 3NCT01701401
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV
A Phase 3 study testing LDV/SOF and RBV in people with Chronic Hepatitis C Virus, run by Gilead Sciences at 88 sites in 7 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed-dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis C Virus
- What is being tested?
- LDV/SOF and RBV
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 870 participants
- Where
- 88 sitesin 7 countries
- Study dates
- Sep 2012to Apr 2014
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18, with chronic genotype 1 HCV infection
- HCV treatment-naive
- HCV RNA > 10,000 IU/mL at screening
- Cirrhosis determination; a liver biopsy may be required
- Screening laboratory values within defined thresholds
- Use of two effective contraception methods if female of childbearing potential or sexually active male
Who cannot join
- Pregnant or nursing female or male with pregnant female partner
- Co-infection with HIV or hepatitis B virus (HBV)
- Current or prior history of clinical hepatic decompensation
- Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)
- Chronic use of systemic immunosuppressive agents
- History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
Trial locations and contacts
88 sites in 7 countries.
88 sites in 7 countries
United States53 sites
Study site
Albuquerque, New Mexico
Study site
Arlington, Texas
Study site
Asheville, North Carolina
Study site
Atlanta, Georgia
Study site
Aurora, Colorado
Study site
Baltimore, Maryland
Study site
Birmingham, Alabama
Study site
Boston, Massachusetts
Study site
Chapel Hill, North Carolina
Study site
Chicago, Illinois
Study site
Cincinnati, Ohio
Study site
Dallas, Texas
Study site
Decatur, Georgia
Study site
Detroit, Michigan
Study site
Durham, North Carolina
Study site
Englewood, Colorado
Study site
Fairfax, Virginia
Study site
Falls Church, Virginia
Study site
Fayetteville, North Carolina
Study site
Gainesville, Florida
Study site
Germantown, Tennessee
Study site
Hillsborough, New Jersey
Study site
Houston, Texas
Study site
Indianapolis, Indiana
Study site
Kansas City, Missouri
Study site
La Jolla, California
Study site
Long Beach, California
Study site
Los Angeles, California
Study site
Lutherville, Maryland
Study site
Manhasset, New York
Study site
Marietta, Georgia
Study site
Miami, Florida
Study site
Nashville, Tennessee
Study site
New York, New York
Study site
Norfolk, Virginia
Study site
Orlando, Florida
Study site
Palo Alto, California
Study site
Philadelphia, Pennsylvania
Study site
Richmond, Virginia
Study site
Rochester, Minnesota
Study site
Sacramento, California
Study site
Saint Paul, Minnesota
Study site
San Antonio, Texas
Study site
San Diego, California
Study site
Santa Fe, New Mexico
Study site
Seattle, Washington
Study site
St Louis, Missouri
Study site
Statesville, North Carolina
Study site
Tampa, Florida
Study site
The Bronx, New York
Study site
Washington D.C., District of Columbia
Study site
Wellington, Florida
Study site
Winston-Salem, North Carolina
Germany9 sites
Study site
Berlin
Study site
Cologne
Study site
Düsseldorf
Study site
Essen
Study site
Frankfurt
Study site
Freiburg im Breisgau
Study site
Hamburg
Study site
Hanover
Study site
Mainz
France8 sites
Study site
CHRU Lille
Study site
Clichy
Study site
Créteil
Study site
La Tronche
Study site
Lyon
Study site
Marseille
Study site
Nice
Study site
Paris
Italy8 sites
Study site
Bologna
Study site
Brescia
Study site
Milan
Study site
Padova
Study site
Palermo
Study site
Roma
Study site
San Giovanni Rotondo
Study site
Torino
Spain5 sites
Study site
Barcelona
Study site
Madrid
Study site
Málaga
Study site
Santander
Study site
Seville
United Kingdom4 sites
Study site
Birmingham, Wstmid
Study site
London
Study site
Manchester
Study site
Plymouth
About this study
Official title: A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination (FDC) +/- Ribavirin for 12 and 24 Weeks in Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection.
The purpose of this study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed-dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection.
- Conditions
- Chronic Hepatitis C Virus
- Being tested
- LDV/SOF, RBV
- Keywords
- HCV genotype 1 (GT-1), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin, Open Label, Sofosbuvir, Additional relevant MeSH terms:, Hepatitis, Hepatitis, Chronic, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Enterovirus Infections
- Medical subject headings
- Hepatitis C, Chronic, Hepatitis, Hepatitis, Chronic, Hepatitis C, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDV/SOFDrug
Also called Harvoni®, GS-5885/GS-7977
LDV/SOF 90/400 mg FDC tablet administered orally once daily
RBVDrug
RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
| Study group | Role | What they receive |
|---|---|---|
| LDV/SOF 12 weeks | Experimental | LDV/SOF administered for 12 weeks Receives: Drug: LDV/SOF |
| LDV/SOF+RBV 12 weeks | Experimental | LDV/SOF+RBV administered for 12 weeks. Receives: Drug: LDV/SOF; Drug: RBV |
| LDV/SOF 24 weeks | Experimental | LDV/SOF administered for 24 weeks Receives: Drug: LDV/SOF |
| LDV/SOF+RBV 24 weeks | Experimental | LDV/SOF+RBV administered for 24 weeks. Receives: Drug: LDV/SOF; Drug: RBV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Study Drug (SVR12)
SVR12 was defined as HCV RNA level < the lower limit of quantification (LLOQ, ie, < 25 copies/mL) 12 weeks after last dose of study drug.
Measured: Posttreatment Week 12
Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug
The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.
Measured: Up to 24 weeks
Secondary outcomes (8)
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Study Drug
SVR4 and SVR24 were defined as HCV RNA level < LLOQ at 4 and 24 weeks after discontinuation of study drug, respectively.
Measured: Posttreatment Weeks 4 and 24
Percentage of Participants With HCV RNA < LLOQ at Week 2
Measured: Week 2
Percentage of Participants With HCV RNA < LLOQ at Week 4
Measured: Week 4
Percentage of Participants With HCV RNA < LLOQ at Week 8
Measured: Week 8
Change From Baseline in HCV RNA at Week 2
Measured: Baseline; Week 2
Change From Baseline in HCV RNA at Week 4
Measured: Baseline; Week 4
Change From Baseline in HCV RNA at Week 8
Measured: Baseline; Week 8
Percentage of Participants With Virologic Failure
On-treatment virologic failure was defined as:
- Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow- up values, OR
- Rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow-up values, OR
- Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment
Virologic relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Measured: Baseline to posttreatment Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2012 (estimated)
- Study startSep 2012
- Primary completionMar 2014
- Study completionApr 2014
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis C VirusStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 870 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jenny Yang, Pharm D, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01701401
- Sponsor's protocol ID
- GS-US-337-0102
- Other IDs
- 2012-003387-43
- Status last verified
- Mar 2015
- First submitted
- 2 Oct 2012
- Last updated
- 16 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
Publications
Grebely J, Mauss S, Brown A, Bronowicki JP, Puoti M, Wyles D, Natha M, Zhu Y, Yang J, Kreter B, Brainard DM, Yun C, Carr V, Dore GJ. Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials. Clin Infect Dis. 2016 Dec 1;63(11):1405-1411. doi: 10.1093/cid/ciw580. Epub 2016 Aug 23.
PubMed 27553375Younossi ZM, Elsheikh E, Stepanova M, Gerber L, Nader F, Stamm LM, Brainard DM, McHutchinson JG. Ledipasvir/sofosbuvir treatment of hepatitis C virus is associated with reduction in serum apolipoprotein levels. J Viral Hepat. 2015 Dec;22(12):977-82. doi: 10.1111/jvh.12448. Epub 2015 Aug 17.
PubMed 26280786Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Brau N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98. doi: 10.1056/NEJMoa1402454. Epub 2014 Apr 11.
PubMed 24725239
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination (FDC) +/- Ribavirin for 12 and 24 Weeks in Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection.
- ClinicalTrials.gov ID
- NCT01701401
- Acronym / sponsor ID
- GS-US-337-0102
- Conditions
- Chronic Hepatitis C Virus
- Keywords
- HCV genotype 1 (GT-1), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 870 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Sep 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 5 Oct 2012 (estimated)
- Results
- Posted 27 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed-dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| LDV/SOF 12 weeks | Experimental | Drug: LDV/SOFLDV/SOF administered for 12 weeks |
| LDV/SOF+RBV 12 weeks | Experimental | Drug: LDV/SOF, Drug: RBVLDV/SOF+RBV administered for 12 weeks. |
| LDV/SOF 24 weeks | Experimental | Drug: LDV/SOFLDV/SOF administered for 24 weeks |
| LDV/SOF+RBV 24 weeks | Experimental | Drug: LDV/SOF, Drug: RBVLDV/SOF+RBV administered for 24 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18, with chronic genotype 1 HCV infection
- HCV treatment-naive
- HCV RNA > 10,000 IU/mL at screening
- Cirrhosis determination; a liver biopsy may be required
- Screening laboratory values within defined thresholds
Key exclusion criteria (6 listed)
- Pregnant or nursing female or male with pregnant female partner
- Co-infection with HIV or hepatitis B virus (HBV)
- Current or prior history of clinical hepatic decompensation
- Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)
- Chronic use of systemic immunosuppressive agents
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 |
|---|---|---|
| LDV/SOFAlso: Harvoni®, GS-5885/GS-7977LDV/SOF 90/400 mg FDC tablet administered orally once daily | Drug | LDV/SOF 12 weeks, LDV/SOF 24 weeks, LDV/SOF+RBV 12 weeks, LDV/SOF+RBV 24 weeks |
| RBVRBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg) | Drug | LDV/SOF+RBV 12 weeks, LDV/SOF+RBV 24 weeks |
Primary outcome
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Study Drug (SVR12)
Time frame: Posttreatment Week 12
SVR12 was defined as HCV RNA level < the lower limit of quantification (LLOQ, ie, < 25 copies/mL) 12 weeks after last dose of study drug.
Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug
Time frame: Up to 24 weeks
The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.
8 secondary outcomes
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Study Drug
Time frame: Posttreatment Weeks 4 and 24
Percentage of Participants With HCV RNA < LLOQ at Week 2
Time frame: Week 2
Percentage of Participants With HCV RNA < LLOQ at Week 4
Time frame: Week 4
Percentage of Participants With HCV RNA < LLOQ at Week 8
Time frame: Week 8
Change From Baseline in HCV RNA at Week 2
Time frame: Baseline; Week 2
Change From Baseline in HCV RNA at Week 4
Time frame: Baseline; Week 4
Change From Baseline in HCV RNA at Week 8
Time frame: Baseline; Week 8
Percentage of Participants With Virologic Failure
Time frame: Baseline to posttreatment Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27553375Grebely J, Mauss S, Brown A, Bronowicki JP, Puoti M, Wyles D, Natha M, Zhu Y, Yang J, Kreter B, Brainard DM, Yun C, Carr V, Dore GJ. Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials. Clin Infect Dis. 2016 Dec 1;63(11):1405-1411. doi: 10.1093/cid/ciw580. Epub 2016 Aug 23.
- Derived from this study: PubMed 26280786Younossi ZM, Elsheikh E, Stepanova M, Gerber L, Nader F, Stamm LM, Brainard DM, McHutchinson JG. Ledipasvir/sofosbuvir treatment of hepatitis C virus is associated with reduction in serum apolipoprotein levels. J Viral Hepat. 2015 Dec;22(12):977-82. doi: 10.1111/jvh.12448. Epub 2015 Aug 17.
- Derived from this study: PubMed 24725239Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Brau N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98. doi: 10.1056/NEJMoa1402454. Epub 2014 Apr 11.
- Individual participant dataSharing planned: Yes. Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
Related trials for Chronic Hepatitis C Virus
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic
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.
Jenny Yang, Pharm D study director
Gilead Sciences
88 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LDV/SOF and RBV in people with Chronic Hepatitis C Virus, run by Gilead Sciences at 88 sites in 7 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 6 inclusion and 6 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 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 88 sites in United States, Germany, France, Italy, Spain and 2 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 27 Mar 2015). 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 With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Study Drug (SVR12) (time frame: Posttreatment Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01701401, which also lists 3 linked publications.
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 16 Nov 2018.