Hepatitis C Infection
Conditions
Keywords
Hepatitis C, SCY-635, Ribavirin, Interferon
Brief summary
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.
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
Interventions
Sponsors
Scynexis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Undetectable HCV RNA | Week 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Undetectable HCV RNA | Week 12 | — |
| Partial Early Virologic Response | Week 12 | Proportion of subjects with detectable HCV RNA that achieve a \> or = 2 log reduction in HCV RNA from baseline to Week 12 |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
Placebo: Oral tablets given bid for 28 days
peginterferon alfa 2a: 180 ug prefilled syringe given once per week for up to 48 weeks
Ribavirin: tablets given bid for up to 48 weeks | 2 |
| SCY-635 600 mg SCY-635 600 mg + PegIFN + RBV for 4 weeks followed by PegIFN + RBV for 20 weeks
SCY-635: SCY-635 tablets, 300 mg bid for 28 days
peginterferon alfa 2a: 180 ug prefilled syringe given once per week for up to 48 weeks
Ribavirin: tablets given bid for up to 48 weeks | 8 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Met stopping rules | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | SCY-635 600 mg |
|---|---|---|---|
| Age, Continuous | 47.0 years STANDARD_DEVIATION 15.56 | 45.1 years STANDARD_DEVIATION 9.29 | 44.6 years STANDARD_DEVIATION 8.67 |
| HCV genotype HCV_1a | 1 participants | 8 participants | 7 participants |
| HCV genotype HCV_1b | 1 participants | 2 participants | 1 participants |
| HCV RNA | 7.21 log10 IU/mL STANDARD_DEVIATION 0.05 | 6.48 log10 IU/mL STANDARD_DEVIATION 0.58 | 6.3 log10 IU/mL STANDARD_DEVIATION 0.49 |
| IL28B genotype IL28B_CT | 2 participants | 8 participants | 6 participants |
| IL28B genotype IL28B_TT | 0 participants | 2 participants | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 8 Participants | 7 Participants |
| Region of Enrollment Puerto Rico | 1 participants | 5 participants | 4 participants |
| Region of Enrollment United States | 1 participants | 5 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 7 / 8 |
| serious Total, serious adverse events | 0 / 2 | 0 / 8 |
Outcome results
Primary
Undetectable HCV RNA
Time frame: Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Undetectable HCV RNA | 0 participants |
| SCY-635 600 mg | Undetectable HCV RNA | 1 participants |
Secondary
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
Time frame: Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Partial Early Virologic Response | 0 participants |
| SCY-635 600 mg | Partial Early Virologic Response | 4 participants |
Secondary
Undetectable HCV RNA
Time frame: Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Undetectable HCV RNA | 0 participants |
| SCY-635 600 mg | Undetectable HCV RNA | 3 participants |
Secondary
Undetectable HCV RNA
Time frame: Week 24
Population: Week 24 analysis does not include the 2 placebo subjects because they were discontinued for lack of efficacy before week 24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCY-635 600 mg | Undetectable HCV RNA | 5 participants |