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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Infection
• Intervention / Treatment: Drug: Placebo; Drug: Pegasys; Drug: Copegus; Drug: SCY-635

Detailed Description

Objectives:

The primary objective of this Phase 2a study was to assess the effect of treatment with SCY-635, used in combination with peginterferon alfa-2a (PegIFN α-2a) and ribavirin (RBV), on hepatitis C viral replication (as measured by quantitative serum HCV RNA) in treatment-naive subjects with chronic genotype 1 infection who have an IL28B genotype of C/T or T/T.

The secondary objective of the study was to evaluate the safety and pharmacokinetics (PK) of SCY-635 when given in combination with PegIFN α-2a and RBV.

Primary Endpoints:

Proportion of subjects in each cohort with an undetectable serum HCV RNA level at Week 4 of treatment

Secondary Endpoints:

Adverse events and clinical laboratory assessments, including tests of liver function Proportion of subjects achieving complete early virologic response (cEVR, defined as an undetectable serum HCV RNA level at Week 12) Proportion of subjects achieving partial early virologic response (pEVR, defined as a detectable serum HCV RNA level with ≥ 2 log10 reduction in serum HCV RNA from Baseline to Week 12) Proportion of subjects achieving an undetectable serum HCV RNA level at Week 24 Pharmacokinetic assessments of SCY-635 when given in combination with PegIFN α-2a and RBV; trough concentrations of PegIFN α-2a and RB

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion de Investigation de Diego
• United States
  • California
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Texas
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Other Names: Batch # BMR/10/731; Drug: Pegasys; 180 ug prefilled syringe given once per week for up to 48 weeks; Drug: Copegus; tablets given bid for up to 48 weeks
Active Comparator: SCY-635 600 mg; SCY-635 600 mg + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks	Drug: Pegasys; 180 ug prefilled syringe given once per week for up to 48 weeks; Drug: Copegus; tablets given bid for up to 48 weeks; Drug: SCY-635; SCY-635 tablets, 300 mg bid for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Undetectable HCV RNA	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Undetectable HCV RNA		Week 24
Undetectable HCV RNA		Week 12
Partial Early Virologic Response	Proportion of subjects with detectable HCV RNA that achieve a > or = 2 log reduction in HCV RNA from baseline to Week 12	Week 12

Collaborators and Investigators

• Sponsor: Scynexis, Inc.
• Investigators: Principal Investigator: Andrew J Muir, MD, Duke Clinical Research Institute; Principal Investigator: Keyur Patel, MD, Duke Clinical Ressearch Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: November 23, 2010
• First Submitted That Met QC Criteria: December 22, 2010
• First Posted (Estimate): December 23, 2010

Study Record Updates

• Last Update Posted (Actual): August 18, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Hepatitis C; Interferon; Ribavirin; SCY-635
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Infections; Hepatitis; Hepatitis A; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2a
• Other Study ID Numbers: SCY-635-201