Cirrhosis, Hepatitis C
Conditions
Keywords
HCV, Genotype 3, Treatment naive, Treatment experienced
Brief summary
This is a randomized, open label, single center safety and efficacy study. At least 40 cirrhotic subjects with HCV genotype 3 will receive standard of care treatment of sofosbuvir and ribavirin (SOF/RBV) as well as 60 mg daily of Daclatasvir (investigational product). Subjects will be randomized in a 1:1 to receive either: * Group A: 16 weeks of DCV/SOF/RBV * Group B: 24 weeks of DCV/SOF/RBV Subjects will return to the study center at various time points throughout the 16 or 24 weeks of treatment in addition to 12 weeks post taking last dose of study drug to monitor safety and efficacy. These visits will be according to standard of care.
Interventions
DRUGdaclatasvir
DRUGSofosbuvir, Sovaldi
DRUGRibavirin
Sponsors
Tarek I. Hassanein, M.D., FACP, FAG, AGAF
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed, written, informed consent must be available from the subject before any study-specific procedures are performed; 2. Male or female 18-75 years of age; 3. All of the following at least 6 months prior to screening visit: * Documented HCV infection based on history of a positive serum anti-HCV antibody test and/or detectable levels of HCV RNA \>= 10,000 IU/mL, and * Documented HCV genotype 3. 4. Subjects with evidence of cirrhosis defined by either a liver biopsy \<= 3 years from screening demonstrating a Metavir Fibrosis Score of F4 (or equivalent); OR Fibroscan® \<= 1 year from screening \> 12.5 kPa. If a subject is evaluated by more than one testing method, then the liver biopsy results take precedence; 5. Women of childbearing potential (WOCBP) must: * have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug. * WOCBP must agree to follow instructions for method(s) of contraception for 7 months post-treatment completion. * Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the following duration for 7 months post-treatment completion. * Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of \< 1% per year when used consistently and correctly. 6. At minimum the subject agrees to the use of two methods of contraception, with at least one method being highly effective as listed below: Highly Effective Methods of Contraception * Male condoms with spermicide * Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena® by male subject's WOCBP partner. Female partners of male subjects participating in the study may use hormone-based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug. WOCBP cannot use hormonal contraception as one of the two methods of contraception because there are no data on the effectiveness of systemic hormonal contraceptives in women taking SOF. However, WOCBP can continue to use hormonal contraceptives, if necessary, in addition to 2 other non-hormonal methods of contraception * Nonhormonal IUDs, such as ParaGard® * Tubal Ligation * Vasectomy * Complete Abstinence - defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs. Subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence. Less Effective Methods of Contraception * Diaphragm with spermicide * Cervical cap with spermicide * Vaginal sponge * Male condom without spermicide * Progestin only pills * Female condom; A male and female condom must not be used together Azoospermic males, women who are not of childbearing potential and WOCBP who abstain from heterosexual activity on a continuous basis, are exempt from contraceptive requirements. However, WOCBP who abstain from heterosexual activity on a continuous basis must still undergo pregnancy testing.
Exclusion criteria
1. Subjects who lack capacity to consent for themselves; 2. HCV Genotypes other than GT-3 infection; mixed genotype infections are not permitted; 3. Liver histology consistent with any other co-existing cause of chronic liver disease (apart from fatty liver and/or Chronic Hepatitis B Virus); 4. Body Mass Index \> 40 at the Screening visit; 5. Any of the following within one month of screening: * Uncontrolled diabetes; * Unstable or uncontrolled thyroid disease (subjects requiring medication to control their thyroid disease are eligible if all other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From baseline (start of study drugs) to last day of taking study drugs; an average of 20 weeks. | This field states the number of participants who had an adverse event |
| Number of Participants With Abnormal Safety Laboratory Tests (ALT and/or Total Bilirubin) That Required Discontinuing Study Drugs | From baseline (start of study drugs) to last day of taking study drugs; an average of 20 weeks. | This field states the number of participants who had an abnormal ALT that required discontinuing study drugs and/or abnormal Total Bilirubin that required discontinuing study drugs. |
| Number of Participants With Undetectable HCV Virus 12 Weeks After Stopping Study Drugs | From baseline (start of study drugs) until 12 weeks after stopping study drugs | Sustained Virologic Response (SVR) defined as undetectable HCV RNA 12 weeks after stopping study drugs. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A - 16 Weeks Combination of sofosbuvir 400 mg daily, ribavirin 1000-1200 mg daily (weight based) and daclatasvir 60 mg daily for 16 weeks
daclatasvir, Daklinza
Sofosbuvir, Sovaldi
Ribavirin | 21 |
| Group B - 24 Weeks Combination of sofosbuvir 400 mg daily, ribavirin 1000-1200 mg daily (weight based) and daclatasvir 60 mg daily for 24 weeks
daclatasvir, Daklinza
Sofosbuvir, Sovaldi
Ribavirin | 18 |
| Total | 39 |
Baseline characteristics
| Characteristic | Group A - 16 Weeks | Group B - 24 Weeks | Total |
|---|---|---|---|
| Age, Continuous | 54.62 years STANDARD_DEVIATION 8.15 | 55.72 years STANDARD_DEVIATION 6.32 | 55.13 years STANDARD_DEVIATION 7.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 5 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 13 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Pre-treatment HCV RNA (viral load) | 3009718.11 IU/mL STANDARD_DEVIATION 3750275.88 | 3165043.17 IU/mL STANDARD_DEVIATION 4871398.73 | 3085281.65 IU/mL STANDARD_DEVIATION 4271365.19 |
| 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 18 Participants | 37 Participants |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 21 | 1 / 18 |
| other Total, other adverse events | 21 / 21 | 18 / 18 |
| serious Total, serious adverse events | 0 / 21 | 2 / 18 |
Outcome results
Primary
Number of Participants With Abnormal Safety Laboratory Tests (ALT and/or Total Bilirubin) That Required Discontinuing Study Drugs
This field states the number of participants who had an abnormal ALT that required discontinuing study drugs and/or abnormal Total Bilirubin that required discontinuing study drugs.
Time frame: From baseline (start of study drugs) to last day of taking study drugs; an average of 20 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - 16 Weeks | Number of Participants With Abnormal Safety Laboratory Tests (ALT and/or Total Bilirubin) That Required Discontinuing Study Drugs | 0 Participants |
| Group B - 24 Weeks | Number of Participants With Abnormal Safety Laboratory Tests (ALT and/or Total Bilirubin) That Required Discontinuing Study Drugs | 0 Participants |
Primary
Number of Participants With Adverse Events
This field states the number of participants who had an adverse event
Time frame: From baseline (start of study drugs) to last day of taking study drugs; an average of 20 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - 16 Weeks | Number of Participants With Adverse Events | 21 Participants |
| Group B - 24 Weeks | Number of Participants With Adverse Events | 18 Participants |
Primary
Number of Participants With Undetectable HCV Virus 12 Weeks After Stopping Study Drugs
Sustained Virologic Response (SVR) defined as undetectable HCV RNA 12 weeks after stopping study drugs.
Time frame: From baseline (start of study drugs) until 12 weeks after stopping study drugs
Population: The analysis covers only the subjects who reached the 12 weeks after stopping study drugs time point. 19 of 21 participants randomized to Group A reached that timepoint and 16 of 18 participants randomized to Group B reached that timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - 16 Weeks | Number of Participants With Undetectable HCV Virus 12 Weeks After Stopping Study Drugs | 19 Participants |
| Group B - 24 Weeks | Number of Participants With Undetectable HCV Virus 12 Weeks After Stopping Study Drugs | 16 Participants |