Chronic Hepatitis CPhase 2NCT00537407
A Study of Debio 025 in Combination With PegIFN Alpha-2a and Ribavirin in Chronic HCV Patients Non-responders to Standard Treatment
A Phase 2 study testing Debio 025, Peg-IFNα2a and Ribavirin in people with Chronic Hepatitis C, run by Debiopharm International SA at 7 sites in United States.
Trial summary
Debio 025 (alisporivir) is an oral cyclophilin inhibitor with a new mechanism of action demonstrating potent anti-hepatitis C virus (HCV) activity in pre-clinical models and patients. The current standard of care (SOC) in HCV patients consists of a combination of peg-IFN alpha and ribavirin. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Debio 025, Peg-IFNα2a and Ribavirin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 7 sitesUnited States
- Study dates
- Sep 2007to Apr 2010
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and female patients between 18 and 60 years of age.
- Hepatitis B negative and human immunodeficiency virus (HIV) negative.
- Diagnosed with hepatitis C genotype I and not responsive to treatments such as peginterferon alpha-2a or 2b and ribavirin for at least 12 weeks.
- Adequate liver function (Child-Pugh-Turcotte score A) and other laboratory parameters within acceptable range.
- Females may participate only if they cannot become pregnant, i.e., are surgically sterile, post-menopausal, or using 2 reliable contraceptive methods.
- Male patients must be surgically sterile or utilizing a barrier contraceptive method.
- For female patients of child bearing potential, negative pregnancy test within 1 week of first investigational product administration.
Who cannot join
- Treatment with any investigational drug within 6 months prior to the start of the study.
- Ongoing or recent use of antiviral medication within 1 month before the start of the study.
- A known bad reaction or intolerance to Debio 025, peginterferon alpha-2a, and/or ribavirin.
- Presence or history of any severe related disease.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
The Johns Hopkins University School of Medicine
Baltimore, Maryland, 21205
Methodist Transplant Physicians
Dallas, Texas, 75203
Metropolitan Research
Fairfax, Virginia, 22031
University of Florida
Gainesville, Florida, 32610
Scripps Clinic Liver Disease Research Center
La Jolla, California, 92037
University of Miami Center for Liver Diseases
Miami, Florida, 33136
Virginia Mason Medical Center
Seattle, Washington, 98101
About this study
Official title: An Open-label, Randomized, 5-arm, Parallel-group Study of the Effects on Viral Kinetics, Safety and Pharmacokinetics of Different Dosing Regimens of Debio 025 in Combination With Peginterferon Alpha-2a and Ribavirin in Chronic HCV Genotype 1 Patients Who Are Non Responders to Standard Peginterferon Alpha and Ribavirin Treatment
Debio 025 (alisporivir) is an oral cyclophilin inhibitor with a new mechanism of action demonstrating potent anti-hepatitis C virus (HCV) activity in pre-clinical models and patients.
The current standard of care (SOC) in HCV patients consists of a combination of peg-IFN alpha and ribavirin. Treatment duration and ribavirin dose depend on the genotype treated. Only 40-50% of patients with genotype 1 achieve a sustained viral response (SVR). This study assesses whether Debio 025 administered in combination with peg-IFN alpha 2a and ribavirin can improve the outcome of treatment in this group of patients.
Read the detailed description
This is a multicentre, open-label, randomized, 5 arm parallel-group, multiple dose study in 50 chronic hepatitis C virus (HCV) genotype 1 non-responders to standard treatment with peg-IFN alpha (2a or 2b) and ribavirin. The entire study lasts a maximum of 96 weeks and consists of a 48- or 72-week treatment period (according to response). A follow-up visit to assess the sustained viral response (SVR) takes place 24 weeks after treatment cessation, i.e., at study Week 72 or 96, or earlier for discontinued study participants.
There were 2 parts in the treatment period. Part 1 lasted from Day 1 to Day 29 (Weeks 1 to 4); Part 2 lasted from Week 5 to Week 48 or 72.
During Part 1 of treatment (Weeks 1 to 4), participants are randomized to 1 of 5 treatment arms and receive 4 weeks of Debio 025 (alisporivir) monotherapy, Debio 025 combined with standard dose peg-IFNα2a, or 1 of 3 triple therapies combining different doses of Debio 025 with peg-IFNα2a and ribavirin at standard doses.
During Part 2 of treatment (Weeks 5 to 48 or 72), participants receive standard doses of peg-IFNα2a/ribavirin dual therapy for 44 or 68 weeks, depending on their response to treatment. At Week 12, participants who do not achieve ≥ 2 log10 decrease in HCV RNA are withdrawn and considered treatment failures. Participants who have undetectable HCV RNA levels and/or ≥ 2 log10 decrease in HCV RNA continue treatment until Week 24. At Week 24, participants who still have detectable HCV RNA levels are withdrawn and considered treatment failures. Participants with undetectable HCV RNA levels at Weeks 12 and 24 continue treatment until Week 48. At Week 24, "slow responders" (defined as participants with a detectable, but > 2 log10 decrease in HCV RNA levels at Week 12 and undetectable levels at Week 24) are eligible to continue treatment until Week 72.
- Conditions
- Chronic Hepatitis C
- Being tested
- Debio 025, Peg-IFNα2a, Ribavirin
- Keywords
- Hepatitis, Hepatitis C
- Medical subject headings
- Hepatitis C, Chronic, Hepatitis, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Debio 025Drug
Also called Alisporivir
Debio 025 supplied as a 100 mg/mL oral solution
Peg-IFNα2aDrug
Also called PEGASYS
Peg-IFNa2a supplied in 180 μg/0.5 mL prefilled syringes
RibavirinDrug
Also called Copegus
Ribavirin supplied as 200 mg tablets
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm A | Experimental | Debio 025 (alisporivir) 400 mg orally once daily + peg-IFNα2a 180 μg subcutaneously (sc) once weekly + ribavirin 1000 or 1200 mg/day orally for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response Receives: Drug: Debio 025; Drug: Peg-IFNα2a; Drug: Ribavirin |
| Treatment Arm B | Experimental | Debio 025 (alisporivir) 400 mg orally once daily for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response Receives: Drug: Debio 025; Drug: Peg-IFNα2a; Drug: Ribavirin |
| Treatment Arm C | Experimental | Debio 025 (alisporivir) 400 mg orally once daily + peg-IFNα2a 180 μg sc once weekly for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response Receives: Drug: Debio 025; Drug: Peg-IFNα2a; Drug: Ribavirin |
| Treatment Arm D | Experimental | Debio 025 (alisporivir) 800 mg orally once daily + peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response Receives: Drug: Debio 025; Drug: Peg-IFNα2a; Drug: Ribavirin |
| Treatment Arm E | Experimental | Debio 025 (alisporivir) orally at a loading dose of 400 mg twice daily for 7 days followed by 400 mg/day for 22 days + peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response Receives: Drug: Debio 025; Drug: Peg-IFNα2a; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in log10 Hepatitis C Virus RNA at Day 29 in the Debio 025 Triple Therapy Treatment Arms (A, D, and E)
Hepatitis C virus RNA was quantified in plasma samples using real time polymerase chain reaction.
Measured: Baseline to Day 29
Secondary outcomes (6)
Change From Baseline in log10 Hepatitis C Virus RNA at Day 29 in the Debio 025 Monotherapy and Dual Therapy Treatment Arms (B and C)
Hepatitis C virus RNA was quantified in plasma samples using real time polymerase chain reaction.
Measured: Baseline to Day 29
log10 Hepatitis C Virus RNA at Day 29
Hepatitis C virus RNA was quantified in plasma samples using real time polymerase chain reaction.
Measured: Day 29
Percentage of Participants With a Rapid Viral Response at Day 29
A participant had a rapid viral response if their viral RNA was undetectable (< 10 IU/mL).
Measured: Day 29
Percentage of Participants With an Early Viral Response at Week 12
A participant had an early viral response if their viral RNA had decreased ≥ 2 log10 at Week 12 compared to Baseline.
Measured: Baseline to Week 12
Percentage of Participants With an End-of-treatment Response at the End of Treatment (Week 48 or 72)
A participant had an end-of-treatment response if their viral RNA was undetectable (< 10 IU/mL).
Measured: End of treatment (Week 48 or 72)
Percentage of Participants With a Sustained Viral Response 24 Weeks After the End of Treatment (Week 72 or 96)
A participant had a sustained viral response if their viral RNA was undetectable (< 10 IU/mL).
Measured: 24 weeks after the end of treatment (Week 72 or 96)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2007 (estimated)
- Study startSep 2007
- Primary completionApr 2010
- Study completionApr 2010
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 Chronic Hepatitis CStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Debiopharm International SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Raf Crabbé, MD, Study director, Debiopharm International S.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00537407
- Sponsor's protocol ID
- Debio 025-HCV-207
- Other IDs
- DEB025A2207
- Status last verified
- Feb 2016
- First submitted
- 28 Sep 2007
- Last updated
- 17 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomized, 5-arm, Parallel-group Study of the Effects on Viral Kinetics, Safety and Pharmacokinetics of Different Dosing Regimens of Debio 025 in Combination With Peginterferon Alpha-2a and Ribavirin in Chronic HCV Genotype 1 Patients Who Are Non Responders to Standard Peginterferon Alpha and Ribavirin Treatment
- ClinicalTrials.gov ID
- NCT00537407
- Acronym / sponsor ID
- Debio 025-HCV-207
- Conditions
- Chronic Hepatitis C
- Keywords
- Hepatitis, Hepatitis C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Debiopharm International SAIndustry (pharma, biotech, devices)
- Study start
- Sep 2007
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 1 Oct 2007 (estimated)
- Results
- Posted 7 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Debio 025 (alisporivir) is an oral cyclophilin inhibitor with a new mechanism of action demonstrating potent anti-hepatitis C virus (HCV) activity in pre-clinical models and patients.
The current standard of care (SOC) in HCV patients consists of a combination of peg-IFN alpha and ribavirin. Treatment duration and ribavirin dose depend on the genotype treated. Only 40-50% of patients with genotype 1 achieve a sustained viral response (SVR). This study assesses whether Debio 025 administered in combination with peg-IFN alpha 2a and ribavirin can improve the outcome of treatment in this group of patients.
Detailed description
This is a multicentre, open-label, randomized, 5 arm parallel-group, multiple dose study in 50 chronic hepatitis C virus (HCV) genotype 1 non-responders to standard treatment with peg-IFN alpha (2a or 2b) and ribavirin. The entire study lasts a maximum of 96 weeks and consists of a 48- or 72-week treatment period (according to response). A follow-up visit to assess the sustained viral response (SVR) takes place 24 weeks after treatment cessation, i.e., at study Week 72 or 96, or earlier for discontinued study participants.
There were 2 parts in the treatment period. Part 1 lasted from Day 1 to Day 29 (Weeks 1 to 4); Part 2 lasted from Week 5 to Week 48 or 72.
During Part 1 of treatment (Weeks 1 to 4), participants are randomized to 1 of 5 treatment arms and receive 4 weeks of Debio 025 (alisporivir) monotherapy, Debio 025 combined with standard dose peg-IFNα2a, or 1 of 3 triple therapies combining different doses of Debio 025 with peg-IFNα2a and ribavirin at standard doses.
During Part 2 of treatment (Weeks 5 to 48 or 72), participants receive standard doses of peg-IFNα2a/ribavirin dual therapy for 44 or 68 weeks, depending on their response to treatment. At Week 12, participants who do not achieve ≥ 2 log10 decrease in HCV RNA are withdrawn and considered treatment failures. Participants who have undetectable HCV RNA levels and/or ≥ 2 log10 decrease in HCV RNA continue treatment until Week 24. At Week 24, participants who still have detectable HCV RNA levels are withdrawn and considered treatment failures. Participants with undetectable HCV RNA levels at Weeks 12 and 24 continue treatment until Week 48. At Week 24, "slow responders" (defined as participants with a detectable, but > 2 log10 decrease in HCV RNA levels at Week 12 and undetectable levels at Week 24) are eligible to continue treatment until Week 72.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm A | Experimental | Drug: Debio 025, Drug: Peg-IFNα2a, Drug: RibavirinDebio 025 (alisporivir) 400 mg orally once daily + peg-IFNα2a 180 μg subcutaneously (sc) once weekly + ribavirin 1000 or 1200 mg/day orally for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response |
| Treatment Arm B | Experimental | Drug: Debio 025, Drug: Peg-IFNα2a, Drug: RibavirinDebio 025 (alisporivir) 400 mg orally once daily for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response |
| Treatment Arm C | Experimental | Drug: Debio 025, Drug: Peg-IFNα2a, Drug: RibavirinDebio 025 (alisporivir) 400 mg orally once daily + peg-IFNα2a 180 μg sc once weekly for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response |
| Treatment Arm D | Experimental | Drug: Debio 025, Drug: Peg-IFNα2a, Drug: RibavirinDebio 025 (alisporivir) 800 mg orally once daily + peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response |
| Treatment Arm E | Experimental | Drug: Debio 025, Drug: Peg-IFNα2a, Drug: RibavirinDebio 025 (alisporivir) orally at a loading dose of 400 mg twice daily for 7 days followed by 400 mg/day for 22 days + peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male and female patients between 18 and 60 years of age.
- Hepatitis B negative and human immunodeficiency virus (HIV) negative.
- Diagnosed with hepatitis C genotype I and not responsive to treatments such as peginterferon alpha-2a or 2b and ribavirin for at least 12 weeks.
- Adequate liver function (Child-Pugh-Turcotte score A) and other laboratory parameters within acceptable range.
- Females may participate only if they cannot become pregnant, i.e., are surgically sterile, post-menopausal, or using 2 reliable contraceptive methods.
Key exclusion criteria (4 listed)
- Treatment with any investigational drug within 6 months prior to the start of the study.
- Ongoing or recent use of antiviral medication within 1 month before the start of the study.
- A known bad reaction or intolerance to Debio 025, peginterferon alpha-2a, and/or ribavirin.
- Presence or history of any severe related disease.
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 |
|---|---|---|
| Debio 025Also: AlisporivirDebio 025 supplied as a 100 mg/mL oral solution | Drug | Treatment Arm A, Treatment Arm B, Treatment Arm C, Treatment Arm D, Treatment Arm E |
| Peg-IFNα2aAlso: PEGASYSPeg-IFNa2a supplied in 180 μg/0.5 mL prefilled syringes | Drug | Treatment Arm A, Treatment Arm B, Treatment Arm C, Treatment Arm D, Treatment Arm E |
| RibavirinAlso: CopegusRibavirin supplied as 200 mg tablets | Drug | Treatment Arm A, Treatment Arm B, Treatment Arm C, Treatment Arm D, Treatment Arm E |
Primary outcome
Change From Baseline in log10 Hepatitis C Virus RNA at Day 29 in the Debio 025 Triple Therapy Treatment Arms (A, D, and E)
Time frame: Baseline to Day 29
Hepatitis C virus RNA was quantified in plasma samples using real time polymerase chain reaction.
6 secondary outcomes
Change From Baseline in log10 Hepatitis C Virus RNA at Day 29 in the Debio 025 Monotherapy and Dual Therapy Treatment Arms (B and C)
Time frame: Baseline to Day 29
log10 Hepatitis C Virus RNA at Day 29
Time frame: Day 29
Percentage of Participants With a Rapid Viral Response at Day 29
Time frame: Day 29
Percentage of Participants With an Early Viral Response at Week 12
Time frame: Baseline to Week 12
Percentage of Participants With an End-of-treatment Response at the End of Treatment (Week 48 or 72)
Time frame: End of treatment (Week 48 or 72)
Percentage of Participants With a Sustained Viral Response 24 Weeks After the End of Treatment (Week 72 or 96)
Time frame: 24 weeks after the end of treatment (Week 72 or 96)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
- 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.
Raf Crabbé, MD study director
Debiopharm International S.A.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Debio 025, Peg-IFNα2a and Ribavirin in people with Chronic Hepatitis C, run by Debiopharm International SA at 7 sites in United States.
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 7 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 Feb 2016. 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. 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 7 May 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?
Change From Baseline in log10 Hepatitis C Virus RNA at Day 29 in the Debio 025 Triple Therapy Treatment Arms (A, D, and E) (time frame: Baseline to Day 29). 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 Feb 2016.