Hepatitis CPhase 2CTS-1027-04NCT01051921
Study of CTS-1027 in Combination With Pegylated Interferon and Ribavirin in Hepatitis C Virus (HCV) Null-Responders
A Phase 2 study testing CTS-1027, Pegylated interferon and Ribavirin in people with Hepatitis C, run by Conatus Pharmaceuticals Inc. at 15 sites in 2 countries.
Trial summary
The purpose of this study is to determine if the combination treatment of CTS-1027, pegylated interferon and ribavirin can improve the response rates in HCV patients who did not previously respond to pegylated interferon and ribavirin therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C
- What is being tested?
- CTS-1027, Pegylated interferon 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
- 67 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Jan 2010to Dec 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and understand and comply with the requirements of the trial
- HCV genotype 1 infected null responders to prior therapy comprised of pegylated interferon and ribavirin (standard of care, SOC) defined as:
- Failure to achieve an early virologic response (< 2 log decline in HCV-RNA by Week 12), or
- If Week 12 HCV-RNA was not obtained but Week 24 was obtained, Week 24 response was < 2 log decline
- Alpha-fetoprotein (AFP) <= 50 ng/mL
- Hemoglobin ≥ 12 g/dL, platelet count ≥ 125 x 10^9/L, and white blood cell count ≥ 1.5 x 10^9/L
- In the opinion of the Principal Investigator, the patient met the 80%/80%/80% rule during the previous pegylated interferon and ribavirin therapy (i.e., received at least 80% of the pegylated interferon and ribavirin doses, at least 80% of the dose size, for at least 80% of the treatment duration)
- Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from screening to at least six months after the completion of the trial.
Who cannot join
- < 2 log decline in HCV-RNA at Week 12 but > 2 log decline at any time from Week 12 to Week 24 during prior therapy with pegylated interferon and ribavirin (prior standard of care therapy)
- Decompensated or severe liver disease defined by one or more of the following criteria:
- Prothrombin time 3 seconds > control
- Direct bilirubin ≥ 1.5 x ULN
- Serum albumin below normal limits
- AST or ALT > 7 x ULN at screening
Show all 30Show fewer
- Evidence of portal hypertension including:
- Varices on esophagogastroduodenoscopy (EGD) with or without a history of gastrointestinal bleeding; or
- Ascites
- Cirrhosis defined by one or both of the following criteria:
- Liver biopsy showing cirrhosis
- Other clinical signs and symptoms suggestive of cirrhosis
- Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or other imaging techniques)
- Clinically significant ocular findings such as retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or other abnormality
- Known history or presence of human immunodeficiency virus (HIV) infection
- Co-infection with hepatitis B virus (HBV)
- If female: pregnant, lactating, or positive serum or urine pregnancy test
- Male partners of women who are currently pregnant
- Renal impairment (creatinine > 1.5 x ULN), creatinine clearance < 50 mL/min, or hepatorenal syndrome with ascites
- Hospitalization for liver disease within 60 days of screening
- History of alcohol abuse (> 50 g per day) within the past year
- History of severe psychiatric disease, especially depression, characterized by:
- Suicide attempt
- Hospitalization for psychiatric disease
- Period of disability as a result of psychiatric disease
- Prior exposure to CTS-1027
- Prior triple treatment comprised of pegylated interferon, ribavirin, and protease and/or polymerase inhibitors
- History or presence of clinically concerning cardiac arrhythmias or prolongation of pre-dose QTc interval of > 450 milliseconds
- Other concomitant disease or condition likely to significantly decrease life expectancy (e.g., moderate to severe congestive heart failure) or any malignancy other than curatively treated skin cancer (basal cell or squamous cell carcinomas), unless adequately treated or in complete remission for ten or more years
- Any patient who has received any investigational drug or device within 30 days of dosing, or who is scheduled to receive another investigational drug or device during the course of this trial.
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
United States14 sites
Digestive Healthcare of Georgia
Atlanta, Georgia, 30309
Consultants of Clinical Research, Ohio GI and Liver Institute
Cincinnati, Ohio, 45219
University of Colorado Health Science Center
Denver, Colorado, 80262
South Denver Gastroenterology
Englewood, Colorado, 80113
Advanced Liver Therapies - Baylor College of Medicine
Houston, Texas, 77030
VA Medical Center, Houston
Houston, Texas, 77030
Scripps Clinic
La Jolla, California, 92037
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
Liver Institute of Virginia
Newport News, Virginia, 23602
Henry Ford Medical Center-Columbus
Novi, Michigan, 48377
MN Clinical Research Center
Plymouth, Minnesota, 55446
University of Utah Health Science Center
Salt Lake City, Utah, 84132
VA Medical Center, San Diego
San Diego, California, 92161
St. Louis University
St Louis, Missouri, 63104
About this study
Official title: An Open-Label Trial of Pegylated Interferon Plus Ribavirin in Combination With CTS-1027 in HCV Null-Responders
The purpose of this study is to determine if the combination treatment of CTS-1027, pegylated interferon and ribavirin can improve the response rates in HCV patients who did not previously respond to pegylated interferon and ribavirin therapy.
Read the detailed description
A subset of non-responders to standard of care treatments (pegylated interferon and ribavrin) is termed null responders. Null responders are the most treatment refractory population. Treatment for null responders is currently limited: retreatment with SOC results in approximately 5% sustained virologic response (SVR).
CTS-1027 may facilitate the activity of interferon by preventing MMP-induced cleavage and deactivation in both phases of clinical response to therapy. In addition, CTS-1027, like ribavirin, alone does not significantly affect viral replication, but both CTS-1027 and ribavirin are likely to impact response to therapy during the second and slower phase of the clinical response.
The potential of MMP inhibition to facilitate the action of interferon, together with ribavirin-driven up-regulation of interferon stimulated genes, has the potential to yield a potent host immune response in this highly resistant null-responder patient population. Again, since MMP inhibition is thought to target the second slower phase kinetics, the initial treatment duration in this trial will be 24 weeks.
This trial will evaluate the safety and efficacy of CTS-1027 combined with SOC in patients who did not previously respond to SOC therapy.
- Conditions
- Hepatitis C
- Being tested
- CTS-1027, Pegylated interferon, Ribavirin
- Keywords
- HCV, Null Responder
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTS-1027Drug
CTS-1027 supplied in 5 and 10 mg tablets, 15 mg taken twice daily, for up to 48 weeks
Pegylated interferonDrug
Also called Pegasys
Pegylated interferon, 180 micrograms in 0.5 ml of solution injected subcutaneously (SQ) once per week, for up to 48 weeks. Packaged in single use syringes.
RibavirinDrug
Also called Copegus
Ribavirin, 200 mg capsules taken in two divided daily doses totaling 1000 mg (5 capsules) for patients weighing 75 kg or less, or 1200 mg (6 capsules) for patients weighing more than 75 kg for up to 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| CTS-1027, Peg IFN, Ribavirin | Experimental | Study drug (CTS-1027) plus Standard of Care treatment (pegylated interferon and ribavirin).
CTS-1027, 15 mg taken twice daily. Pegylated interferon, 180 μg injected once a week. Ribavirin, 1000 mg or 1200 mg daily (depending on patient weight), taken in two divided doses. Receives: Drug: CTS-1027; Drug: Pegylated interferon; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Virologic Response (EVR)
Early Virologic Response (EVR) is defined as the percent of patients who experienced a drop in HCV-RNA (Hepatitis C Ribonucleic acid, also known as "viral load") levels of more that 2 log from before treatment (baseline) through 12 Weeks of treatment.
Measured: Baseline and Study week 12
Secondary outcomes (1)
> 2 Log Decline in Hepatitis C Virus Ribonucleic Acid (HCV-RNA) at 24 Weeks
Percent of patients experiencing a drop in HCV-RNA Hepatitis C virus ribonucleic acid, also known as "viral load") levels in the blood equal to, or greater than, 2 log from before treatment (baseline) through 24 weeks of treatment.
Measured: Baseline and Study week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2010 (estimated)
- Study startJan 2010
- Primary completionNov 2011
- Study completionDec 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.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Conatus Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Erin Castelloe, MD, Study chair, Conatus Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01051921
- Sponsor's protocol ID
- CTS-1027-04
- Acronym
- CTS-1027-04
- Status last verified
- Apr 2012
- First submitted
- 18 Jan 2010
- Last updated
- 16 Apr 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Trial of Pegylated Interferon Plus Ribavirin in Combination With CTS-1027 in HCV Null-Responders
- ClinicalTrials.gov ID
- NCT01051921
- Acronym / sponsor ID
- CTS-1027-04 / CTS-1027-04
- Conditions
- Hepatitis C
- Keywords
- HCV, Null Responder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Conatus Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2010
- Primary completion
- Nov 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 20 Jan 2010 (estimated)
- Results
- Posted 10 Apr 2012
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 determine if the combination treatment of CTS-1027, pegylated interferon and ribavirin can improve the response rates in HCV patients who did not previously respond to pegylated interferon and ribavirin therapy.
Detailed description
A subset of non-responders to standard of care treatments (pegylated interferon and ribavrin) is termed null responders. Null responders are the most treatment refractory population. Treatment for null responders is currently limited: retreatment with SOC results in approximately 5% sustained virologic response (SVR).
CTS-1027 may facilitate the activity of interferon by preventing MMP-induced cleavage and deactivation in both phases of clinical response to therapy. In addition, CTS-1027, like ribavirin, alone does not significantly affect viral replication, but both CTS-1027 and ribavirin are likely to impact response to therapy during the second and slower phase of the clinical response.
The potential of MMP inhibition to facilitate the action of interferon, together with ribavirin-driven up-regulation of interferon stimulated genes, has the potential to yield a potent host immune response in this highly resistant null-responder patient population. Again, since MMP inhibition is thought to target the second slower phase kinetics, the initial treatment duration in this trial will be 24 weeks.
This trial will evaluate the safety and efficacy of CTS-1027 combined with SOC in patients who did not previously respond to SOC therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CTS-1027, Peg IFN, Ribavirin | Experimental | Drug: CTS-1027, Drug: Pegylated interferon, Drug: RibavirinStudy drug (CTS-1027) plus Standard of Care treatment (pegylated interferon and ribavirin). CTS-1027, 15 mg taken twice daily. Pegylated interferon, 180 μg injected once a week. Ribavirin, 1000 mg or 1200 mg daily (depending on patient weight), taken in two divided doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female patients of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and understand and comply with the requirements of the trial
- HCV genotype 1 infected null responders to prior therapy comprised of pegylated interferon and ribavirin (standard of care, SOC) defined as:
- Alpha-fetoprotein (AFP) <= 50 ng/mL
- Hemoglobin ≥ 12 g/dL, platelet count ≥ 125 x 10^9/L, and white blood cell count ≥ 1.5 x 10^9/L
- In the opinion of the Principal Investigator, the patient met the 80%/80%/80% rule during the previous pegylated interferon and ribavirin therapy (i.e., received at least 80% of the pegylated interferon and ribavirin doses, at least 80% of the dose size, for at least 80% of the treatment duration)
Key exclusion criteria (30 listed)
- < 2 log decline in HCV-RNA at Week 12 but > 2 log decline at any time from Week 12 to Week 24 during prior therapy with pegylated interferon and ribavirin (prior standard of care therapy)
- Decompensated or severe liver disease defined by one or more of the following criteria:
- Evidence of portal hypertension including:
- Cirrhosis defined by one or both of the following criteria:
- Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or other imaging techniques)
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 |
|---|---|---|
| CTS-1027CTS-1027 supplied in 5 and 10 mg tablets, 15 mg taken twice daily, for up to 48 weeks | Drug | CTS-1027, Peg IFN, Ribavirin |
| Pegylated interferonAlso: PegasysPegylated interferon, 180 micrograms in 0.5 ml of solution injected subcutaneously (SQ) once per week, for up to 48 weeks. Packaged in single use syringes. | Drug | CTS-1027, Peg IFN, Ribavirin |
| RibavirinAlso: CopegusRibavirin, 200 mg capsules taken in two divided daily doses totaling 1000 mg (5 capsules) for patients weighing 75 kg or less, or 1200 mg (6 capsules) for patients weighing more than 75 kg for up to 48 weeks. | Drug | CTS-1027, Peg IFN, Ribavirin |
Primary outcome
Early Virologic Response (EVR)
Time frame: Baseline and Study week 12
Early Virologic Response (EVR) is defined as the percent of patients who experienced a drop in HCV-RNA (Hepatitis C Ribonucleic acid, also known as "viral load") levels of more that 2 log from before treatment (baseline) through 12 Weeks of treatment.
1 secondary outcome
> 2 Log Decline in Hepatitis C Virus Ribonucleic Acid (HCV-RNA) at 24 Weeks
Time frame: Baseline and Study week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2012.
- 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.
Erin Castelloe, MD study chair
Conatus Pharmaceuticals Inc.
15 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 CTS-1027, Pegylated interferon and Ribavirin in people with Hepatitis C, run by Conatus Pharmaceuticals Inc. at 15 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 8 inclusion and 30 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 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 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 10 Apr 2012). 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?
Early Virologic Response (EVR) (time frame: Baseline and Study week 12). 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 16 Apr 2012.