Friday, April 15, 2011

Hepatitis C; Highlighting Conatus' Drug CTS-1027

 Today on the blog Conatus' drug CTS-1027 will be highlighted, with media updates, EASL 24-week interim results, which consisted of Conatus' drug CTS-1027 in combination with Pegasys® and ribavirin (Copegus®) in HCV genotype 1 null-responder patient population. It's unusual for an early phase trial to be composed around null responders. A possible bonus is the anti-inflammatory and anti-fibrotic effects the company claims that CTS-1027 has, which is exciting. Right now there are a number of companies involved in hepatitis C drug development , you can view them here.

 Included in this entry is a link to the companies Phase 2b trial, which as you may know is currently recruiting approximately 260 patients, at up to fifty medical centers in the U.S. (locations are listed below). Also included is additional information on the drug from Conatus' web site.

On this blogs web site is a Summary of  investigational Hepatitis C drugs presented at this months EASL and a comprehensive list of Hepatitis Clinical Trials.

Conatus Pharmaceuticals recently announced funding is in place to advance the development of CTS-1027.
See Link;
Conatus Adds $7.5M, Closes Series B Round
April 14
San Diego’s Conatus Pharmaceuticals says it has closed the Series B round of funding that began in February with a $7.5 million investment by MPM Capital of South San Francisco, CA. In a statement yesterday, the company says it has raised a total of $32.5 million in this round. Conatus plans to use the proceeds to advance development of CTS-1027, a new drug candidate for treating hepatitis C that the company licensed from F. Hoffman-La Roche, and to evaluate compounds acquired from Idun Pharmaceuticals last year. The hepatitis C compound is currently in multiple mid-stage clinical trials.

CTS-1027 for Liver Disease

CTS-1027 is a novel and proprietary oral small molecule that inhibits the activity of key members of a class of proteases, the matrix metalloproteases or MMPs. Excessive MMP activity has been demonstrated to occur in the liver in response to HCV infection. Data from our laboratory taken together with data in the literature suggest that MMP activity in HCV-infected patients could play multiple roles in shifting the balance toward sustained virus replication and away from host-mediated viral clearance. Conatus believes that HCV regulates MMP levels and activity in order to efficiently infect hepatocytes and to interfere with the host interferon response. MMP inhibitors can be effective counter-measures against HCV directly, by inhibiting new infections, and indirectly, by amplifying the antiviral effects of interferon. This intervention would impact both the clearance of HCV-infected cells and the appearance of newly infected cells that over time could lead to reduction or elimination of circulating virus and ultimately all virus-infected cells. CTS-1027 has unique potential to impact HCV survival strategies and provide significant benefit to the HCV-infected patient population.

CTS-1027 Preclinical Summary
CTS-1027 is a potent small molecule inhibitor of MMPs. It inhibits individual members of the MMP family that are believed to be important in inflammation and tissue damage. CTS-1027 was specifically designed, however, not to inhibit MMP 1, as inhibition of MMP 1 was believed to be associated with musculoskeletal side effects.

Results of studies conducted in preclinical models of hepatitis and fibrogenesis provide support for the potential usefulness of CTS-1027 in patients with chronic hepatitis C virus infection. Although there are no non-primate comprehensive models of HCV infection, various aspects of the pathogenesis in man can be studied preclinically, and CTS-1027 has effects that could lead to benefit in patients. CTS-1027 inhibits HCV infection in primary human hepatocytes when added before or after HCV infection.

In the murine bile-duct ligation model of liver fibrosis, CTS-1027 significantly reduced collagen deposition, number of bile infarcts, apoptotic hepatocytes, and hepatocytes positive for activated caspases 3/7. Biomarkers of fibrogenesis and activation of stellate cells were also reduced. CTS-1027 also prevented elevations of plasma alanine aminotransferase (ALT) levels in acute hepatitis induced by tumor necrosis factor alpha (TNF-α)/D-galactosamine (Gln), activating Fas antibody, Concanavalin A (Con A), or lipopolysaccharride (LPS)/Gln.

Overall, the results of these different preclinical models of hepatitis suggest that CTS-1027 is hepatoprotective, blocks HCV replication, reduces inflammatory and fibrogenic responses associated with a variety of hepatic injuries, and may provide benefit to patients with chronic hepatitis C virus infection. The table below summarizes the preclinical experiments that have been conducted with CTS-1027 in liver disease.

CTS-1027 Clinical Summary

More than 700 subjects (including healthy volunteers, patients with osteoarthritis and HCV patients) have been exposed to one or more doses of CTS-1027. Single dose exposures were as high as 700 mg, while multiple dose exposures have included up to 315 mg once a day for 28 days, and 150 mg once a day for 24 weeks in osteoarthritis patients.

A number of investigational trials have been conducted to test the tolerability of CTS-1027 in the hepatitis C patient population and to explore potential efficacy. Initial efficacy measures were surrogate markers presuming an anti-inflammatory and anti-fibrogenic mechanism of action. Based on additional preclinical data, antiviral endpoints are now also being explored. The therapeutic trials are summarized briefly in the table below and described in more detail in the paragraphs that follow.

CTS-1027-01 (completed)CTS-1027-03 (completed)CTS-1027-04 (in progress)CTS-1027-05 (in progress)
Drug(s)CTS-1027 monotherapyCTS-1027 +/- RibavirinIFN/Ribavirin + CTS-1027IFN/Ribavirin + CTS-1027 or Placebo
DurationVariable24 WeeksUp to 48 WeeksUp to 48 Weeks
Patient PopulationHCV infected patientsIFN treatment naïveIFN/Ribavirin null respondersIFN/Ribavirin null responders
Population MixHeterogeneous, but enriched for poor IFN respondersBroadest patient groupPurest IFN refractory populationPurest IFN refractory population
(Expected) OutcomeIdentify dose for future trials, observed some evidence of antiviral responseSignificant viral load decrease coupled with decrease in ALT/AST≥ 2 log reduction @ week 24, viral clearance @ wk 48, SVR @ wk 72SVR @ wk 72, viral clearance @ wk 48

CTS 1027 as Monotherapy (Trials CTS-1027-01 and CTS-1027-03)

CTS-1027 has been studied in patients with chronic hepatitis C infection, both in treatment naïve patients for whom interferon is not appropriate, and in those who previously failed to respond to SOC (treatment failures). Various doses and dosing regimens were tested initially to confirm the tolerability of twice daily dosing. It was determined that 15 mg BID (twice a day) is a well-tolerated dose for chronic administration in HCV patients. A subset of patients experienced a transient elevation in aminotransferases, followed by a transient fall in HCV-RNA. This was not a safety signal as ALT levels declined with continued exposure to drug. While these observations are anecdotal, they are consistent with CTS-1027 playing a role in overcoming immune tolerance in chronically-infected patients. Sentinel aminotransferase spikes have been reported in acutely infected HCV human patients who clear the virus spontaneously. It is also a phenomenon that precedes viral clearance in human hepatitis B infection (see figure below).

Pattern of ALT flares and HCV-RNA reductions: spontaneous clearance (adapted from Hoofnagle, Hepatology; 2002, 35, S21).

CTS-1027 with Ribavirin (Clinical Trial CTS-1027-03)

A significant proportion of HCV patients are either deemed unsuitable or decline to be treated with IFN-containing therapies. CTS-1027 was studied in this unserved patient population alone and in combination with ribavirin. Ribavirin is well established as a critical component of current and future therapies for HCV. Although understanding its mechanisms remains an area of active research, it is believed that ribavirin integrates into the HCV genome to generate mutations and reduces the overall infectivity of the virus. Ribavirin is known to stimulate IFN responsive genes in HCV patients, but has little to no effect on viral load when administered as a monotherapy. The potential stabilization and facilitation of the action of endogenously produced IFN via MMP inhibition, in concert with ribavirin driven up-regulation of interferon stimulated genes, may yield a potent antiviral response. Therefore, the clinical impact of the combined activities of CTS-1027 and ribavirin, neither of which alone significantly affects viral replication, is likely to occur during the second, slower phase of the clinical response. Trial CTS-1027-03 was designed to test whether CTS-1027 alone or in combination with ribavirin (also a second phase blocker) has an antiviral effect in interferon naïve patients with 24 weeks of treatment.

This study began in June 2009. Patients were randomized to receive 15 mg CTS-1027 BID + placebo, or 15 mg CTS-1027 BID + ribavirin for 24 weeks (30 patients per arm). While the primary endpoint was measurement of serum HCV RNA (viral load), CTS-1027, alone or in combination with ribavirin, was also evaluated for its potential anti-fibrogenic effects (normalization of aminotransferase enzymes).
Topline data from this trial show improvement in key markers for liver damage in both arms, coupled with significant reductions in HCV viral load over the course of the 24 weeks in patients treated with CTS-1027 plus ribavirin. These data support the potential use of CTS-1027 in combination with ribavirin as a long term anti-fibrotic therapy to treat liver damage in this patient population and set the stage for inclusion of CTS-1027 in future all-oral cocktails containing Direct Antiviral Agents (DAAs). Final data analysis from this trial is expected to be completed later this year.

CTS-1027 with IFN + Ribavirin (Clinical Trial CTS-1027-04)

Collective clinical experience in the treatment of patients with chronic HCV has demonstrated that patients who fail to achieve a 2 log reduction at 12 weeks have an especially low likelihood of achieving an SVR. A significant subset of treatment failure patients fall into this category. These patients, classified as "null" responders in the figure below, have few treatment options.

Graph of responses to SOC treatment with table showing success rate of retreatment of the null responder population.

The preclinical experiments in the replicon assay showing a synergistic effect of CTS-1027 with interferon, taken together with patient data from Trials CTS-1027-01 and -03, suggest that CTS-1027 might enhance the response to endogenous or exogenous interferon.

 In Trial CTS-1027-04, initiated in January 2010, Conatus is studying the effects of CTS-1027 in combination with SOC in patients who are null responders (patients who fail to achieve a 2 log reduction at 12 weeks) to SOC.

 It is a single-arm pilot study in 60 patients, using historical controls (described in the table below), and is designed to explore the interferon amplifying activity of CTS-1027. Viral load after 4, 12 and 24 weeks of dosing CTS-1027 (15 mg BID) combined with SOC will be compared to historical response to repeat SOC therapy. Patients with reductions in HCV RNA of at least 2 log units at week 24 will continue treatment for an additional 24 weeks with additional follow-up to determine SVR. IL-28B screening data will be obtained at week 24, which will allow determination of potential differences in responses to CTS-1027 + SOC due to polymorphisms at this locus.

SOC null responder retreatment (data adapted from Rustgi et al. Hepatology 2009; 50: 1719).

4 Weeks
12 Weeks
24 Weeks
48 Weeks
72 Weeks
SOC Historical Responses0%5%

HCV RNA below quantifiable limit for RVR, cEVR, CVR, EOT and SVR
HCV RNA > 2 logs reduced for EVR

Given it is likely that one or more protease or polymerase inhibitors (DAA) will become part of SOC in the near future, it is possible that Phase 3 trials in combination with this new SOC may be necessary. It is important to note that null responder patients are not necessarily good candidates for DAA therapy, as recent data from trials with telaprevir have shown that a significant proportion of these patients have viral breakthrough or relapse during triple therapy.

If the CTS-1027-04 data show a significant antiviral effect of SOC plus CTS-1027 in the null responder population, CTS-1027 may be a useful addition to the soon to be approved triple therapies of SOC plus DAAs.

The Data  CTS-1027-04/ The 24-week interim results

Published: Thursday, Mar. 31, 2011 - 12:08 pm

Full Press Release
CTS-1027 Plus Pegasys/Riba geno 1 null-responder 24-week interim results in hepatitis C patients

CTS 1027 in combination with Peginterferon Alpha-2a (Pegasys®) and ribavirin (Copegus®)-
Trial CTS-1027-04

CTS 1027 in combination with Peginterferon Alpha-2a (Pegasys®) and ribavirin (Copegus®) in a treatment experienced, hepatitis C virus (HCV) null-responder patient population. Null-responder patients are the most difficult to treat patient population and are clinically defined as those patients failing to achieve an early virologic response (EVR) when undergoing treatment with the current standard of care (SOC; pegylated interferon and ribavirin). EVR is defined as at least a 2 log decline in HCV-RNA by week 12 of SOC treatment.

The CTS-1027-04 clinical trial enrolled 67 HCV genotype 1 null-responder patients.

The clinical trial is a single arm and open label design with sustained viral response (SVR; no detectable virus 24 weeks after the end of treatment) as its primary end point.

At week 12, 51% (31/61) of patients receiving 15 mg twice a day of CTS-1027 in addition to standard doses of Pegasys® and Copegus® achieved an EVR on a per protocol (PP) basis. HCV-RNA was below quantifiable limit (BQL) in 5 patients (8.2%, PP) at week 12 and increased to 17 patients (34%, 17/50, PP) at week 24.

This clinical trial is ongoing and final SVR results are expected in 2011.

Data from the CTS-1027-04 clinical trial were presented at the 46th annual meeting of the European Association for the Study of the Liver (EASL) held in Berlin, Germany.

Posters Presented at EASL 2011:

24-Week Treatment With CTS-1027 in Combination With Ribavirin Reduces HCV-RNA in Treatment Naive Genotype-1 Patients. M. Chojkier, G. Everson, A. Muir, B. Bacon, M. Rodriguez-Torres, M. Bennett, M. Fried, S. Gordon, J. Gross, D. Nelson, L. Balart11, M. Jonas, G. Szabo, J. Bloomer, A. McCullough, L. Nyberg, C. Smith, O. Boehm, E. Castelloe, M. Huyghe, S. Mento, P. Contreras, A. Fox, R. Cross, A. Spada

Unique Pattern of Virologic Response in Patients With Genotype-1 HCV: A Phase II Study of CTS-1027 in Combination With Peginteferon Alpha-2A and Ribavirin in Null Responders. M. Rodriguez-Torres, B. Bacon, S. Gordon, R. Rubin, T. Box, M. Kugelmas, J. Vierling, B. Yoffe, P. Pockros, G. Everson, M. Jonas, L. Balart, O. Boehm, E. Castelloe, M. Huyghe, S. Mento, A. Spada, AW. Fox, M. Chojkier

From Clinical

(CTS-1027-05) Trial Recruiting Participants

CTS-1027 is an oral, small molecule compound that inhibits the activity of key members of a class of protease enzymes, the matrix metalloproteinases (MMPs).

The trial will evaluate the safety, tolerability, and antiviral activity of the triple combination after up to 48 weeks of therapy.

The Phase 2b clinical trial (CTS-1027-05) will test CTS-1027 at higher doses in combination with Pegasys® and Copegus® in the null-responder genotype 1 patient population

The placebo-controlled, multicentre, double-blind, randomised trial will enroll approximately 260 patients who will receive Peginterferon Alfa-2a (Pegasys) and ribavirin (Copegus) with or without CTS-1027.

See Link For Full Information;
Standard of Care (SOC) With or Without CTS-1027 in Hepatitis C (HCV) Null-Responders

This study is currently recruiting participants.

Verified on April 2011 by Conatus Pharmaceuticals Inc.


United States, Alabama

University of Alabama at Birmingham Recruiting

Birmingham, Alabama, United States, 35294

Contact: Olivia Hogue, RN, BSN 205-934-1224

Principal Investigator: Omar Massoud, MD

United States, California

Southern California Liver Centers Recruiting

Coronado, California, United States, 92118

Contact: Ileana Rubio 619-522-0330

Principal Investigator: Tarek Hassanein, MD

Scripps Clinic Recruiting

La Jolla, California, United States, 92037

Contact: Shari Gilbert, RN, BSN, MA 858-652-5421

Principal Investigator: Paul Pockros, MD

Loma Linda University MC Recruiting

Loma Linda, California, United States, 92354

Contact: Delia Lujan, LVN, CCRP 909-558-3656

Principal Investigator: Mohamd El Kabany, MD

Huntington Medical Research Institute Recruiting

Pasadena, California, United States, 91105

Contact: Roberta Fitzgerald 626-397-5820

Principal Investigator: Myron Tong, MD

UCSD Recruiting

San Diego, California, United States, 92161

Contact: Monique Gagnon 858-552-8585 ext 7216

Principal Investigator: Mario Chojkier, MD

Medical Associates Research Group Recruiting

San Diego, California, United States, 92123

Contact: Dianne Tuohy 858-277-5678

Principal Investigator: Michael Bennett, MD

United States, Colorado

University of Colorado Denver Recruiting

Aurora, Colorado, United States, 80045

Contact: Jennifer DeSanto, RN 303-724-1861

Principal Investigator: Greg Everson, MD

United States, Connecticut

Yale University School of Medicine Recruiting

New Haven, Connecticut, United States, 06520

Contact: Danielle Jacques 203-785-7031

Principal Investigator: Michael Schilsky, MD

United States, Florida

University of Miami Not yet recruiting

Miami, Florida, United States, 33136

Contact: Dimitri Duvilaire 305-243-6939

Principal Investigator: Eugene R. Schiff, MD

United States, Georgia

Atlanta Medical Center, Inc. Recruiting

Atlanta, Georgia, United States, 30309

Contact: Alona Waldrop-Kelly 404-428-2970

Principal Investigator: Brian Pearlman, MD

Liver Center of Atlanta Recruiting

Atlanta, Georgia, United States, 30309

Contact: Julie Costello, CCRP 404-355-3200 ext 166

Principal Investigator: Raymond Rubin, MD

United States, Illinois

Rush University Medical Center Recruiting

Chicago, Illinois, United States, 60612

Contact: Bridget Galetti, RN, BSN, CCRC 312-563-3919

Principal Investigator: Nikunj Shah, MD

Loyola University Recruiting

Maywood, Illinois, United States, 60153

Contact: Cathy Kalnicky, RN, BSN, CCRP 708-216-2027

Principal Investigator: Marty Cohen, MD

United States, Indiana

Indiana University School of Medicine Recruiting

Indianapolis, Indiana, United States, 46201

Contact: Virginia Blevins 317-278-1872

Principal Investigator: Paul Y. Kwo, MD

United States, Kansas

University of Kansas Medical Center Recruiting

Kansas City, Kansas, United States, 66160

Contact: Scott Stanley 913-588-0296

Principal Investigator: Richard Gilroy, MD

United States, Kentucky

University of Louisville Not yet recruiting

Louisville, Kentucky, United States, 40202

Contact: Mary R Salem, MA, RN 502-852-5547

Principal Investigator: Luis Marsano, MD

United States, Louisiana

Ochsner Clinic Foundation Not yet recruiting

New Orleans, Louisiana, United States, 70121

Contact: Christine Maier, BA, CCRC 504-842-2709

Principal Investigator: Shobha Joshi, MD

Tulane University Health Sciences Center Recruiting

New Orleans, Louisiana, United States, 70112

Contact: Melissa Spedale 504-988-1346

Principal Investigator: Luis Balart, MD

United States, Massachusetts

Beth Israel Deaconess Medical Center Recruiting

Boston, Massachusetts, United States, 02215

Contact: Sheila A Wilson 617-632-1086

Principal Investigator: Nezam H. Afdhal, MD

University of Massachusetts Memorial Medical Center Recruiting

Worcester, Massachusetts, United States, 01655

Contact: Donna Giansiracusa, RN, CCRC 774-441-7648

Principal Investigator: Nadeem Anwar, MD

United States, Michigan

Henry Ford Hospital Recruiting

Detroit, Michigan, United States, 48202-2689

Contact: Diana Thornbury, RN, BSN 248-344-2355

Principal Investigator: Stuart C. Gordon, MD

United States, Minnesota

Mayo Clinic Recruiting

Rochester, Minnesota, United States, 55905

Contact: Linda M. Stadheim, RN 507-284-0141

Principal Investigator: John B. Gross Jr., MD

United States, Missouri

St. Louis University Recruiting

St. Louis, Missouri, United States, 63104

Contact: Doreen Garabedian, RN, CCRC 314-977-9394

Principal Investigator: Bruce Bacon, MD

United States, New York

Einstein College of Medicine (Jacobi Medical Center) Recruiting

Bronx, New York, United States, 10461

Contact: Claudia Calderon, RN 718-918-3577

Principal Investigator: Douglas Simon, MD

Columbia Presbyterian Medical Center Recruiting

New York, New York, United States, 10032

Contact: Sumerah Bakhsh 212-304-5684

Principal Investigator: Robert Brown, MD

Weill Medical College of Cornell Recruiting

New York, New York, United States, 10021

Contact: Christine Cervini 212-746-9822

Principal Investigator: Maya Gambarin-Gelwan, MD

New York University Recruiting

New York, New York, United States, 10016

Contact: Tom Hahambis 212-263-3643

Principal Investigator: Samuel Sigal, MD

Concorde Medical Group Recruiting

New York, New York, United States, 10016

Contact: Maureen Haskins 212-889-5544 ext 152

Principal Investigator: Hillel Tobias, MD

New York Medical College Recruiting

Valhalla, New York, United States, 10595

Contact: Ana R. Casellas, RN 914-594-3439  

Principal Investigator: Edward Lebovics, MD

United States, North Carolina

Duke University Medical Center Recruiting

Durham, North Carolina, United States, 27710

Contact: April Seward, RN 919-681-8852

Principal Investigator: Andrew J. Muir, MD

United States, Ohio

Consultants for Clinical Research Recruiting

Cincinnati, Ohio, United States, 45219

Contact: Andrea Neff, RN 513-872-4549

Principal Investigator: Mark Jonas, MD

Cleveland Clinic Not yet recruiting

Cleveland, Ohio, United States, 44195

Contact: Ruth Sargent, RN 216-444-3126

Principal Investigator: Arthur J. McCullough, MD

United States, Pennsylvania

Albert Einstein Medical Center Recruiting

Philadelphia, Pennsylvania, United States, 19141

Contact: Stacey Carmody, CCRP 215-456-7534

Principal Investigator: Victor Araya, MD

United States, Texas

Baylor All Saints Medical Center Recruiting

Fort Worth, Texas, United States, 76104

Contact: Erin Fassett, RN, MSN, MBA 817-922-7667

Principal Investigator: Stevan Gonzalez, MD

University of Texas Medical Branch at Galveston Recruiting

Galveston, Texas, United States, 77555

Contact: Betty Shipp, RN 409-772-4896

Principal Investigator: Andrea Duchini, MD

University of Texas HSC at Houston Recruiting

Houston, Texas, United States, 77030

Contact: Stacy Burk 713-500-5232

Principal Investigator: Michael B. Fallon, MD

Research Specialists of Texas Recruiting

Houston, Texas, United States, 77030

Contact: Herman Ortiz, LVN, CCRC 713-634-5114

Principal Investigator: Joseph Galati, MD

St. Luke's Episcopal Hospital Recruiting

Houston, Texas, United States, 77030

Contact: Jessica Wilson, MA 832-355-8966

Principal Investigator: John Vierling, MD

VAMC Houston Recruiting

Houston, Texas, United States, 77030

Contact: Kethy Garza-Gasitashvili 713-791-1414 ext 561

Principal Investigator: Boris Yoffe, MD

United States, Utah

University of Utah Recruiting

Salt Lake City, Utah, United States, 84132

Contact: Lindsey Waddoups 801-587-9050

Principal Investigator: Terry Box, MD

United States, Virginia

Metropolitan Research Group Washington DC Recruiting

Fairfax, Virginia, United States, 22031

Contact: Becky Dawson, BS 703-698-9254 ext 20

Principal Investigator: Vinod K. Rustgi, MD

INOVA Health Care Services Washington DC Recruiting

Falls Church, Virginia, United States, 22042

Contact: Mir Heshaam, MD 703-776-4171

Principal Investigator: Zobair Younossi, MD

Liver Institute of Virginia Recruiting

Newport News, Virginia, United States, 23602

Contact: Diane M Hutson 757-947-3190

Principal Investigator: Mitchell L. Shiffman, MD

Virginia Commonwealth University (VCU) Recruiting

Richmond, Virginia, United States, 23298

Contact: Kimberly Williams 804-675-6848

Principal Investigator: Velimir Luketic, MD

United States, Washington

Benaroya Research Institute at Virginia Mason Recruiting

Seattle, Washington, United States, 98101

Contact: Cheryl Shaw, MPH, CCRC 206-341-1786

Principal Investigator: Kris Kowdley, MD


Inclusion Criteria:

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 study

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, post Week 12 HCV-RNA response was < 2 log decline

Screening HCV-RNA viral load of > 5.0 log (i.e., >100,000 IU/mL)

alpha-fetoprotein (AFP) less than or equal to 100 ng/mL

Hemoglobin greater than or equal to 12 g/dL for women and greater than or equal to 13 g/dL for men, hemoglobin A1c less than or equal to 7.5 %, platelet count greater than or equal to 90 x 109/L, and white blood cell count greater than or equal to 1.5 x 109/L

Thyroid Stimulating Hormone (TSH) within normal limits

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 study.

Exclusion Criteria:

< 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 4 seconds > control or INR > 1.2

Total bilirubin ≥ 1.5 mg/dL or direct bilirubin ≥ 1 mg/dL

Serum albumin below normal limits

AST or ALT > 5 x ULN at screening

Presence of ascites

Hepatic encephalopathy

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 10 Renal impairment (creatinine > 1.2 x ULN), serum 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

Patients who qualify as a null-responder based on treatment(s) other than pegylated interferon and ribavirin

History or presence of clinically concerning cardiac arrhythmias or prolongation of pre-dose QTc interval of > 450 milliseconds

History of or current autoimmune disease

Diagnosis of or symptoms suggestive of fibromyalgia

Currently on liver transplantation waiting list or recipient of any organ transplant

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 five or more years

Exposure to any other investigational treatment for any aspect of disease associated with HCV during the past 6 months

Exposure to any investigational drug or device within 30 days of dosing, or scheduled receipt of another investigational drug or device during the course of this study.

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