Study of SCY-635, Pegasys and Copegus in Hepatitis C

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Scynexis Incorporated
ClinicalTrials.gov Identifier:
NCT01265511
First received: November 23, 2010
Last updated: May 29, 2012
Last verified: May 2012
  Purpose

This study will examine the effectiveness of 28 days of triple combination therapy including SCY-635 with peginterferon alfa 2a and ribavirin in reducing serum HCV RNA levels. An additional 20 weeks of treatment with the currently approved standard of care will be offered to all participants. The Week 24 visit will be the last on-study visit. After the Week 24 visit, all subjects with undetectable HCV RNA will be given the option to continue treatment with standard of care for an additional 24 weeks (out to Week 48) under the care of their Principal Investigator.


Condition Intervention Phase
Hepatitis C Infection
Drug: Placebo
Drug: SCY-635
Drug: peginterferon alfa 2a
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2a Study of SCY-635 in Combination With Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naive Subjects With Genotype 1 Hepatitis C Infection

Resource links provided by NLM:


Further study details as provided by Scynexis Incorporated:

Primary Outcome Measures:
  • Undetectable HCV RNA [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Undetectable HCV RNA [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Partial early virologic response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Proportion of subjects with detectable HCV RNA that achieve a > or = 2 log reduction in HCV RNA from baseline to Week 12

  • Undetectable HCV RNA [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Incidence and severity of treatment emergent adverse events and changes in laboratory values as measures of Safety and tolerability [ Time Frame: through Week 24 of the study ] [ Designated as safety issue: Yes ]
    Assessed by determining incidence and severity of adverse events, changes in physical examinations, vital signs, 12 lead electrocardiograms (ECGs), and laboratory assessments (serum chemistry, hematology, and urinalysis)

  • Pharmacokinetic assessment of SCY-635 [ Time Frame: throughout first 8 weeks of treatment ] [ Designated as safety issue: No ]
    On Day 1 and Day 28, serial blood samples for assessing the pharmacokinetics of SCY 635 will be collected prior to the morning dose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Primary PK parameters include AUC(0-12), Cmax, Tmax, and Cavg. Trough concentrations of SCY-635 will be measured on Days 7, 14, and 21 and at Week 8.

  • Pharmacokinetics of peginterferon alfa 2a and Ribavirin (trough concentrations) [ Time Frame: throughout first 8 weeks of treatment ] [ Designated as safety issue: No ]
    Trough concentrations of PegIFN alfa 2a and RBV will be measured on Days 7, 14, 21 and 28 and at Week 8. No other pharmacokinetic parameters will be determined.


Enrollment: 11
Study Start Date: November 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
Drug: Placebo
Oral tablets given bid for 28 days
Drug: peginterferon alfa 2a
180 ug prefilled syringe given once per week for up to 48 weeks
Other Name: Pegasys, PegIFN
Drug: Ribavirin
tablets given bid for up to 48 weeks
Other Name: Copegus, RBV
Active Comparator: SCY-635 600 mg
SCY-635 600 mg + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
Drug: SCY-635
SCY-635 tablets, 300 mg bid for 28 days
Drug: peginterferon alfa 2a
180 ug prefilled syringe given once per week for up to 48 weeks
Other Name: Pegasys, PegIFN
Drug: Ribavirin
tablets given bid for up to 48 weeks
Other Name: Copegus, RBV

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Quantifiable serum levels of HCV-specific RNA in excess of 100,000 IU/mL
  • Chronic HCV status
  • HCV genotype 1 infection and IL28B genotype of C/T or T/T
  • Liver biopsy results within 3 years prior to screening indicating the absence of cirrhosis

    *If no previous biopsy is available, a biopsy must be performed during the screening period to qualify for randomization

  • Body mass index (BMI) between 18 and 38 kg/m2
  • Laboratory variables within acceptable ranges:

    • ALT/AST < 3 × ULN;
    • HgB > 12g/dL for females, > 13 g/dL for males;
    • total WBC count > 3000/mm3 and ANC > 1500/mm3;
    • platelets > 100,000/mm3;
    • prothrombin time (or INR) ≤ 1.2 × ULN;
    • serum albumin ≥ 3.4 g/dL;
    • total bilirubin WNL;
    • serum creatinine WNL; if serum creatinine is > ULN, then calculated creatinine clearance must be > 100 mL/min (by Cockcroft-Gault formula) for subject to be eligible
  • Subjects of childbearing potential (i.e., not surgically sterile or postmenopausal) must agree to use 2 forms of contraception from Screening until 24 weeks after completion of treatment with RBV
  • Negative urine testing for amphetamines and cocaine at Screening.
  • If female, the subject has a negative pregnancy test at Screening and on study Day 1

Exclusion Criteria:

  • History of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease
  • Females who are pregnant or breastfeeding
  • Males with partners who are pregnant or are planning to become pregnant
  • HCV genotype other than genotype 1 and an IL28B genotype of C/C
  • Seropositive for HIV-1 or HIV-2 or hepatitis B virus (HBV) surface antigen (HBsAg)
  • Use of any investigational agent within 3 months prior to dosing
  • Received any prior FDA-approved or investigational drug or drug regimen for the treatment of hepatitis C
  • Evidence of cirrhosis on a previous liver biopsy
  • Evidence of decompensated liver disease
  • Recipient of an organ transplant
  • Evidence of hepatocellular carcinoma
  • Evidence of ongoing alcohol or substance abuse
  • Poorly-controlled diabetes mellitus
  • Congestive heart failure or unstable cardiopulmonary condition, renal disease, or hemoglobinopathy (sickle cell anemia or thalassemia
  • History of seizure disorder
  • History of severe psychiatric illness, including severe depression, history of suicidal ideation, suicidal attempts, related hospitalizations, bipolar disorder, or psychosis requiring medication
  • Concurrent medical condition or laboratory abnormality that would constitute a contra-indication for interferon use
  • History of unstable thyroid disease that would preclude administration of interferon-based therapy
  • Medical condition that requires use of systemic corticosteroids
  • Received warfarin or other anticoagulants during the 21 days immediately prior to Screening, or is expected to require warfarin or other anticoagulants during the study.
  • One or more additional known primary or secondary causes of liver disease, other than hepatitis C
  • Any other concurrent medical condition likely to preclude compliance with the schedule of evaluations, or likely to confound the efficacy or safety observations
  • 12-lead ECG showing the following:

    • Corrected QTc interval ≥ 450 msec (Bazett's correction);
    • QRS > 120 msec;
    • Clinically significant abnormalities;
  • Severe retinopathy or other significant ophthalmological disorder
  • Use of any herbal supplements within 28 days prior to dosing.
  • The use of CYP3A inducers or inhibitors for at least 2 weeks prior to initiation of treatment through Week 6
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01265511

Locations
United States, California
Quest Clinical Research
San Francisco, California, United States, 94115
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Texas
Alamo Medical Research
San Antonio, Texas, United States, 78215
Puerto Rico
Fundacion de Investigation de Diego
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Scynexis Incorporated
Investigators
Principal Investigator: Andrew J Muir, MD Duke Clinical Research Institute
Principal Investigator: Keyur Patel, MD Duke Clinical Ressearch Institute
  More Information

No publications provided

Responsible Party: Scynexis Incorporated
ClinicalTrials.gov Identifier: NCT01265511     History of Changes
Other Study ID Numbers: SCY-635-201
Study First Received: November 23, 2010
Last Updated: May 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Scynexis Incorporated:
Hepatitis C
SCY-635
Ribavirin
Interferon

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 20, 2014