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

• Sponsor: Scynexis, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01265511
• Collaborator: (none)
• Enrollment: 10
• Locations: 4
• Arms: 2
• Duration (Months): 11
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Infection	Drug: Placebo; Drug: SCY-635; Drug: Pegasys; Drug: Copegus	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

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: SCY-635; SCY-635 tablets, 300 mg bid for 28 days; 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

Outcome Measures

Primary Outcome Measures

1. Undetectable HCV RNA [Week 4]

Secondary Outcome Measures

1. Undetectable HCV RNA [Week 12]

2. 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

3. Undetectable HCV RNA [Week 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Quest Clinical Research	San Francisco	California	United States	94115
2	Duke University Medical Center	Durham	North Carolina	United States	27710
3	Alamo Medical Research	San Antonio	Texas	United States	78215
4	Fundacion de Investigation de Diego	San Juan		Puerto Rico	00927

Sponsors and Collaborators

• Scynexis, Inc.

Investigators

• Principal Investigator: Andrew J Muir, MD, Duke Clinical Research Institute
• Principal Investigator: Keyur Patel, MD, Duke Clinical Ressearch Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Scynexis, Inc.
• ClinicalTrials.gov Identifier: NCT01265511
• Other Study ID Numbers: SCY-635-201
• First Posted: Dec 23, 2010
• Last Update Posted: Aug 18, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by Scynexis, Inc.: Hepatitis C; SCY-635; Ribavirin; Interferon
• Additional relevant MeSH terms: Infections; Hepatitis A; Hepatitis C; Hepatitis; Peginterferon alfa-2a

Study Results

Participant Flow

Arm/Group Title	Placebo	SCY-635 600 mg
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	2	8
COMPLETED	0	5
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Placebo	SCY-635 600 mg	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	2	8	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.0 (15.56)	44.6 (8.67)	45.1 (9.29)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 25%	2 20%
Male	2 100%	6 75%	8 80%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 50%	0 0%	1 10%
White	1 50%	7 87.5%	8 80%
More than one race	0 0%	1 12.5%	1 10%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 50%	4 50%	5 50%
Puerto Rico	1 50%	4 50%	5 50%
IL28B genotype (participants) [Number]
IL28B_CT	2 100%	6 75%	8 80%
IL28B_TT	0 0%	2 25%	2 20%
HCV genotype (participants) [Number]
HCV_1a	1 50%	7 87.5%	8 80%
HCV_1b	1 50%	1 12.5%	2 20%
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	7.21 (0.05)	6.3 (0.49)	6.48 (0.58)

Outcome Measures

1. Primary Outcome

Title	Undetectable HCV RNA
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	SCY-635 600 mg
Arm/Group Description	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	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
Measure Participants	2	8
Number [participants]	0 0%	1 12.5%

2. Secondary Outcome

Title	Undetectable HCV RNA
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	SCY-635 600 mg
Arm/Group Description	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	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
Measure Participants	2	8
Number [participants]	0 0%	3 37.5%

3. Secondary Outcome

Title	Partial Early Virologic Response
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	SCY-635 600 mg
Arm/Group Description	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	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
Measure Participants	2	8
Number [participants]	0 0%	4 50%

4. Secondary Outcome

Title	Undetectable HCV RNA
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Week 24 analysis does not include the 2 placebo subjects because they were discontinued for lack of efficacy before week 24.

Arm/Group Title	Placebo	SCY-635 600 mg
Arm/Group Description	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	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
Measure Participants	0	8
Number [participants]	5 250%

Adverse Events

Time Frame	24 weeks
Arm/Group Title	Placebo		SCY-635 600 mg
Arm/Group Description	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		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
All Cause Mortality
	Placebo		SCY-635 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		SCY-635 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		SCY-635 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		7/8 (87.5%)
Blood and lymphatic system disorders
neutropenia	0/2 (0%)		3/8 (37.5%)
Anaemia	1/2 (50%)		2/8 (25%)
General disorders
Fatigue	1/2 (50%)		2/8 (25%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/2 (0%)		2/8 (25%)
Nervous system disorders
Headache	0/2 (0%)		3/8 (37.5%)
Psychiatric disorders
Insomnia	1/2 (50%)		1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Cough	0/2 (0%)		2/8 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.