Hepatitis C
Conditions
Brief summary
The purpose of the study is to determine if the combination of Daclatasvir, Sofosbuvir and Ribavirin for 12 or 16 weeks is safe and effective in the treatment of Genotype 3 Chronic Hepatitis C (HCV) in patients with advanced fibrosis or compensated cirrhosis. Patients in this study may have already been treated prior for HCV or may have never received treatment for their HCV.
Interventions
DRUGDaclatasvir
DRUGSofosbuvir
DRUGRibavirin
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Must have Genotype 3 Chronic HCV * Must have advanced fibrosis (F3) or compensated cirrhosis (F4) * HCV RNA Viral load ≥ 10,000 IU/mL * HCV Treatment naive or treatment-experienced
Exclusion criteria
* Non Genotype 3 or mixed genotypes * Non advanced fibrosis or compensated cirrhosis * Any prior treatment with NS5A inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 12 (SVR12) | Follow-up Week 12 | SVR12, defined as percentage of participants with hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) at follow-up Week 12. SVR12 imputation was based on Next Value Carried Backwards (NVCB) approach. HCV RNA measurements were excluded after the start of non-study anti-HCV medication on treatment or during follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 4 (SVR4) and Follow-up Week 24 (SVR24) | Follow-up Weeks 4 and 24 | SVR4, defined as percentage of participants with hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) at follow-up Week 4. SVR24, defined as percentage of participants with hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) at follow-up Week 24. SVR4 imputation was based on Next Value Carried Backwards (NVCB) approach. SVR24 imputation was based on missing being treated as non-responder. HCV RNA measurements were excluded after the start of non-study anti-HCV medication on treatment or during follow-up. |
| Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Date of First Dose of Study Drug to 7 Days post last dose of study drug (up to 13 weeks or 17 weeks depending on the randomized treatment group) | Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. The degree of the adverse event or laboratory abnormality are evaluated by grades: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Grading as per using National Cancer Institute Common Terminology Criteria (NCI CTC) Version 3.0 criteria. |
Countries
Australia, France
Participant flow
Recruitment details
53 participants were enrolled. 50 participants were randomized and treated (24 to 12 week arm, 26 to 16 week arm). Reason for non-randomization was 3 no longer met study criteria.
Participants by arm
| Arm | Count |
|---|---|
| Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) Treatment-naïve and treatment-experienced participants with HCV Genotype 3 infection and advanced fibrosis or compensated cirrhosis (F3 or F4) were treated for 12 weeks with oral dosing of Daclatasvir (DCV) 60mg once daily, Sofosbuvir (SOF) 400mg once daily, and Ribavirin (RBV) 1000-1200mg (weight based dosing) split into am and pm dosing. Participants received either 400 mg (2 tablets for participants \< 75 kg) or 600 mg (3 tablets for participants ≥ 75 kg) of RBV in the morning with food and 600 mg (3 tablets) of RBV in the evening with food. After the completion of the 12 week treatment period, participants were followed off treatment for 24 weeks. mg=milligram; kg=kilogram | 24 |
| Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) Treatment-naïve and treatment-experienced participants with HCV Genotype 3 infection and advanced fibrosis or compensated cirrhosis (F3 or F4) were treated for 16 weeks with oral dosing of Daclatasvir (DCV) 60mg once daily, Sofosbuvir (SOF) 400mg once daily, and Ribavirin (RBV) 1000-1200mg (weight based dosing) split into am and pm dosing. Participants received either 400 mg (2 tablets for participants \< 75 kg) or 600 mg (3 tablets for participants ≥ 75 kg) of RBV in the morning with food and 600 mg (3 tablets) of RBV in the evening with food. After the completion of the 16 week treatment period, participants were followed off treatment for 24 weeks. mg=milligram; kg=kilogram | 26 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) | Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) | Total |
|---|---|---|---|
| Age, Continuous | 53.0 years STANDARD_DEVIATION 7.77 | 55.0 years STANDARD_DEVIATION 5.75 | 54.1 years STANDARD_DEVIATION 6.8 |
| Age, Customized <65 | 23 participants | 26 participants | 49 participants |
| Age, Customized >=65 | 1 participants | 0 participants | 1 participants |
| Gender Female | 6 Participants | 4 Participants | 10 Participants |
| Gender Male | 18 Participants | 22 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 24 | 22 / 26 |
| serious Total, serious adverse events | 2 / 24 | 3 / 26 |
Outcome results
Primary
Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 12 (SVR12)
SVR12, defined as percentage of participants with hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) at follow-up Week 12. SVR12 imputation was based on Next Value Carried Backwards (NVCB) approach. HCV RNA measurements were excluded after the start of non-study anti-HCV medication on treatment or during follow-up.
Time frame: Follow-up Week 12
Population: All treated participants: Enrolled participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) | Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 12 (SVR12) | 87.5 percentage of participants |
| Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) | Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 12 (SVR12) | 92.3 percentage of participants |
Secondary
Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities
Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. The degree of the adverse event or laboratory abnormality are evaluated by grades: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Grading as per using National Cancer Institute Common Terminology Criteria (NCI CTC) Version 3.0 criteria.
Time frame: Date of First Dose of Study Drug to 7 Days post last dose of study drug (up to 13 weeks or 17 weeks depending on the randomized treatment group)
Population: All treated participants: Enrolled participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Death | 1 participants |
| Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Discontinuation due to AEs | 0 participants |
| Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Grade 3/4 AEs | 2 participants |
| Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Grade 3/4 Laboratory Abnormalities | 1 participants |
| Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | SAEs | 2 participants |
| Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Grade 3/4 Laboratory Abnormalities | 2 participants |
| Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Death | 0 participants |
| Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | SAEs | 3 participants |
| Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Grade 3/4 AEs | 2 participants |
| Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) | Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Discontinuation due to AEs | 0 participants |
Secondary
Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 4 (SVR4) and Follow-up Week 24 (SVR24)
SVR4, defined as percentage of participants with hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) at follow-up Week 4. SVR24, defined as percentage of participants with hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) at follow-up Week 24. SVR4 imputation was based on Next Value Carried Backwards (NVCB) approach. SVR24 imputation was based on missing being treated as non-responder. HCV RNA measurements were excluded after the start of non-study anti-HCV medication on treatment or during follow-up.
Time frame: Follow-up Weeks 4 and 24
Population: All treated participants: Enrolled participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) | Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 4 (SVR4) and Follow-up Week 24 (SVR24) | Follow-up Week 4 (SVR4) | 87.5 percentage of participants |
| Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) | Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 4 (SVR4) and Follow-up Week 24 (SVR24) | Follow-up Week 24 (SVR24) | 87.5 percentage of participants |
| Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) | Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 4 (SVR4) and Follow-up Week 24 (SVR24) | Follow-up Week 4 (SVR4) | 96.2 percentage of participants |
| Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) | Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 4 (SVR4) and Follow-up Week 24 (SVR24) | Follow-up Week 24 (SVR24) | 92.3 percentage of participants |