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.
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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 monotherapy | CTS-1027 +/- Ribavirin | IFN/Ribavirin + CTS-1027 | IFN/Ribavirin + CTS-1027 or Placebo |
| Duration | Variable | 24 Weeks | Up to 48 Weeks | Up to 48 Weeks |
| Patient Population | HCV infected patients | IFN treatment naïve | IFN/Ribavirin null responders | IFN/Ribavirin null responders |
| Population Mix | Heterogeneous, but enriched for poor IFN responders | Broadest patient group | Purest IFN refractory population | Purest IFN refractory population |
| (Expected) Outcome | Identify dose for future trials, observed some evidence of antiviral response | Significant viral load decrease coupled with decrease in ALT/AST | ≥ 2 log reduction @ week 24, viral clearance @ wk 48, SVR @ wk 72 | SVR @ 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.
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)
Graph of responses to SOC treatment with table showing success rate of retreatment of the null responder population.
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 (RVR) | 12 Weeks (cEVR) (EVR) | 24 Weeks (CVR) | 48 Weeks (EOT) | 72 Weeks (SVR) | |
|---|---|---|---|---|---|
| SOC Historical Responses | 0% | 5% 15% | ≤15% | 15% | 5% |
HCV RNA below quantifiable limit for RVR, cEVR, CVR, EOT and SVR
HCV RNA > 2 logs reduced for EVR
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®)-
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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 Trials.gov
(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.
Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Olivia Hogue, RN, BSN 205-934-1224 ohogue@uab.edu
Principal Investigator: Omar Massoud, MD
United States, California
Southern California Liver Centers Recruiting
Coronado, California, United States, 92118
Contact: Ileana Rubio 619-522-0330 irubio@livercenters.com
Principal Investigator: Tarek Hassanein, MD
Scripps Clinic Recruiting
La Jolla, California, United States, 92037
Contact: Shari Gilbert, RN, BSN, MA 858-652-5421 gilbert.shari@scrippshealth.org
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 robertaf@hmri.org
Principal Investigator: Myron Tong, MD
UCSD Recruiting
San Diego, California, United States, 92161
Contact: Monique Gagnon 858-552-8585 ext 7216 Monique.Gagnon@va.gov
Principal Investigator: Mario Chojkier, MD
Medical Associates Research Group Recruiting
San Diego, California, United States, 92123
Contact: Dianne Tuohy 858-277-5678 dianne.tuohy@marginc.com
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 Jennifer.DeSanto@ucdenver.edu
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 danielle.lettieri@yale.edu
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 dduvilaire@med.miami.edu
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 waldrop-kelly@comcast.net
Principal Investigator: Brian Pearlman, MD
Liver Center of Atlanta Recruiting
Atlanta, Georgia, United States, 30309
Contact: Julie Costello, CCRP 404-355-3200 ext 166 julie.costello2@piedmont.org
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 Bridget_Galetti@rush.edu
Principal Investigator: Nikunj Shah, MD
Loyola University Recruiting
Maywood, Illinois, United States, 60153
Contact: Cathy Kalnicky, RN, BSN, CCRP 708-216-2027 ckalnic@lumc.edu
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 vblevins@iupui.edu
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 sstanley@kumc.edu
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 mary.salem@louisville.edu
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 cmaier@ochsner.org
Principal Investigator: Shobha Joshi, MD
Tulane University Health Sciences Center Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Melissa Spedale 504-988-1346 mspedale@tulane.edu
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 sawilson@bidmc.harvard.edu
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 giansd01@ummhc.org
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 dthornb1@hfhs.org
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 stadheim.linda@mayo.edu
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 dgarabed@slu.edu
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 cmc9003@med.cornell.edu
Principal Investigator: Maya Gambarin-Gelwan, MD
New York University Recruiting
New York, New York, United States, 10016
Contact: Tom Hahambis 212-263-3643 sagapao04@gmail.com
Principal Investigator: Samuel Sigal, MD
Concorde Medical Group Recruiting
New York, New York, United States, 10016
Contact: Maureen Haskins 212-889-5544 ext 152 mhaskins@concordmed.com
Principal Investigator: Hillel Tobias, MD
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Ana R. Casellas, RN 914-594-3439 ana_casellas@nymc.edu
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 april.seward@duke.edu
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 aneff@ccrstudy.com
Principal Investigator: Mark Jonas, MD
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Ruth Sargent, RN 216-444-3126 sargenr@ccf.org
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 carmodys@einstein.edu
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 erinf@baylorhealth.edu
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 bjshipp@utmb.edu
Principal Investigator: Andrea Duchini, MD
University of Texas HSC at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Stacy Burk 713-500-5232 Stacy.Burk@uth.tmc.edu
Principal Investigator: Michael B. Fallon, MD
Research Specialists of Texas Recruiting
Houston, Texas, United States, 77030
Contact: Herman Ortiz, LVN, CCRC 713-634-5114 hortiz@texasliver.com
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 garzagas@bcm.tmc.edu
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 lindsey.waddoups@hsc.utah.edu
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 bdawson@metrohepgi.com
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 heshaam.mir@inova.org
Principal Investigator: Zobair Younossi, MD
Liver Institute of Virginia Recruiting
Newport News, Virginia, United States, 23602
Contact: Diane M Hutson 757-947-3190 Diane_Hutson@bshsi.org
Principal Investigator: Mitchell L. Shiffman, MD
Virginia Commonwealth University (VCU) Recruiting
Richmond, Virginia, United States, 23298
Contact: Kimberly Williams 804-675-6848 kimberly.williams1@va.gov
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 cheryl.shaw@vmmc.org
Principal Investigator: Kris Kowdley, MD
Criteria
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.
http://www.clinicaltrials.gov/ct2/show/NCT01273064?term=cts-1027&rank=3
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