Hepatitis C
Conditions
Brief summary
The purpose of the study is to determine whether the combination of Daclatasvir (DCV), Asunaprevir (ASV), BMS-791325 and Sofosbuvir is effective and safe in treating Hepatitis-C virus.
Detailed description
Allocation: Initial Therapy: Randomized Controlled Trial: Participants are assigned to intervention groups by chance Rescue Therapy: Nonrandomized Trial: Participants are expressly assigned to intervention groups through a non-random method such as physician choice Number of Arms: Initial Therapy: 2 Groups Rescue Therapy: 2 Groups
Interventions
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * Males and Females ≥18 years of age, inclusive * Chronic HCV infection Genotype 1 only * Non-cirrhotic * Treatment naive subjects with no previous exposure to an Interferon formulation (ie, IFNα, pegIFNα), ribavirin (RBV) or HCV Direct Acting Antiviral (DAA) (protease, polymerase inhibitor, etc.)
Exclusion criteria
* HCV Genotype other than Genotype 1 * Documented or suspected hepatocellular carcinoma * Evidence of decompensated liver disease * Contraindication(s) to Peg/RBV therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 (SVR12) | 12 Weeks after treatment discontinuation (Follow-up Week 12) | SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) \< lower limit of quantitation (LLOQ) target detected (TD) or not detected (TND) at post-treatment follow-up Week 12. Imputed SVR12 was based on Next Value Carried Backwards approach. |
| Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment | From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months) | SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect. |
| Number of Participants With Selected Grade 3/4 Laboratory Abnormalities | From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months) | Grade 3/4 laboratory abnormalities (hematology, electrolyte, lipase, liver function, metabolic, renal function, urinalysis). The Week 24 data set was used to evaluate the Week-24 on-treatment safety. The cumulative data set was used to evaluate the safety while on treatment. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b | Post-treatment Week 12 | Percentage of Participants who Achieved SVR12 Associated with HCV geno subtype 1a or 1b |
| Percentage of Participants With End of Treatment Response (EOTR) | End of the treatment | EOTR was defined as HCV RNA less than the lower limit of quantitation, target detected or not detected at end of treatment. |
| Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype) | Post-treatment Week 12 | Percentage of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported. |
| Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24) | Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24). |
| Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2, 4, 12 and 24 | Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), and 24 (SVR24). |
Countries
United States
Participant flow
Pre-assignment details
35 participants enrolled in the study, 28 were randomized. Of the 7 not randomized, 1 participant withdrew consent and 6 no longer met study criteria
Participants by arm
| Arm | Count |
|---|---|
| 4 Weeks DCV 3DAA + SOF Oral dose of a fixed dose combination regimen administered as 1 tablet BID comprising of 30 mg daclatasvir, 200 mg asunaprevir, and 75 mg beclabuvir (referred to as DCV 3DAA), plus sofosbuvir 400 mg 1 tablet daily for 4 weeks (treatment period). Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment. | 14 |
| 6 Weeks DCV 3DAA + SOF Oral dose of a fixed dose combination regimen administered as 1 tablet BID comprising of 30 mg daclatasvir, 200 mg asunaprevir, and 75 mg beclabuvir, plus sofosbuvir 400 mg 1 tablet daily for 6 weeks (treatment period). Thereafter, participants entered a follow-up period of 24 weeks after completion of study treatment or upon early discontinuation of treatment. | 14 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period | Lack of Efficacy | 10 | 6 |
Baseline characteristics
| Characteristic | 6 Weeks DCV 3DAA + SOF | Total | 4 Weeks DCV 3DAA + SOF |
|---|---|---|---|
| Age, Continuous | 59.0 years | 58.5 years | 58.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 13 Participants | 25 Participants | 12 Participants |
| Sex: Female, Male Female | 8 Participants | 17 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 11 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 5 / 14 | 11 / 14 |
| serious Total, serious adverse events | 1 / 14 | 0 / 14 |
Outcome results
Primary
Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment
SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect.
Time frame: From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
Population: Safety population included participants who received at least 1 dose of study therapy (DCV 3DAA or SOF).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 4 Weeks DCV 3DAA + SOF | Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment | Serious Adverse Events | 1 Participants |
| 4 Weeks DCV 3DAA + SOF | Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment | Death | 0 Participants |
| 4 Weeks DCV 3DAA + SOF | Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment | AEs Leading to Discontinuation | 0 Participants |
| 6 Weeks DCV 3DAA + SOF | Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment | Serious Adverse Events | 0 Participants |
| 6 Weeks DCV 3DAA + SOF | Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment | Death | 0 Participants |
| 6 Weeks DCV 3DAA + SOF | Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment | AEs Leading to Discontinuation | 0 Participants |
Primary
Number of Participants With Selected Grade 3/4 Laboratory Abnormalities
Grade 3/4 laboratory abnormalities (hematology, electrolyte, lipase, liver function, metabolic, renal function, urinalysis). The Week 24 data set was used to evaluate the Week-24 on-treatment safety. The cumulative data set was used to evaluate the safety while on treatment. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death.
Time frame: From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
Population: Safety analysis population included participants who received at least 1 dose of study therapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 Weeks DCV 3DAA + SOF | Number of Participants With Selected Grade 3/4 Laboratory Abnormalities | 0 Participants |
| 6 Weeks DCV 3DAA + SOF | Number of Participants With Selected Grade 3/4 Laboratory Abnormalities | 0 Participants |
Primary
Percentage of Participants With Sustained Virologic Response 12 (SVR12)
SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) \< lower limit of quantitation (LLOQ) target detected (TD) or not detected (TND) at post-treatment follow-up Week 12. Imputed SVR12 was based on Next Value Carried Backwards approach.
Time frame: 12 Weeks after treatment discontinuation (Follow-up Week 12)
Population: It included treated participants (randomized participants) who received at least 1 dose of study therapy (DCV 3DAA or SOF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants With Sustained Virologic Response 12 (SVR12) | 28.6 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants With Sustained Virologic Response 12 (SVR12) | 57.1 Percentage of participants |
Secondary
Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND
Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24).
Time frame: Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24)
Population: It included modified Intent-to-treat treated population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Follow-Up Week 2 | 78.6 Percentage of Participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Week 1 | 35.7 Percentage of Participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Follow-Up Week 4 | 42.9 Percentage of Participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Week 4 | 100.0 Percentage of Participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Follow-Up Week 12 | 28.6 Percentage of Participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Week 6 | NA Percentage of Participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Follow-Up Week 24 | 28.6 Percentage of Participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Week 2 | 78.6 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Follow-Up Week 24 | 57.1 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Week 1 | 71.4 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Week 2 | 100.0 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Week 6 | 100.0 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Follow-Up Week 2 | 100.0 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Follow-Up Week 4 | 78.6 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Follow-Up Week 12 | 57.1 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Week 4 | 100.0 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved HCV RNA < LLOQ TND
Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), and 24 (SVR24).
Time frame: Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2, 4, 12 and 24
Population: It included modified ITT treated population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Week 1 | 21.4 Percentage of participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Week 2 | 42.9 Percentage of participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Follow-Up Week 2 | 71.4 Percentage of participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Follow-Up Week 12 | 28.6 Percentage of participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Follow-Up Week 24 | 28.6 Percentage of participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Week 4 | 92.9 Percentage of participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Week 6 | NA Percentage of participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Follow-Up Week 4 | 42.9 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Follow-Up Week 4 | 71.4 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Week 1 | 7.1 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Follow-Up Week 24 | 57.1 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Week 2 | 64.3 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Week 6 | 100.0 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Follow-Up Week 2 | 92.9 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Week 4 | 100.0 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Follow-Up Week 12 | 57.1 Percentage of participants |
Secondary
Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b
Percentage of Participants who Achieved SVR12 Associated with HCV geno subtype 1a or 1b
Time frame: Post-treatment Week 12
Population: All included treated participants. Here n' signifies number of participants analysed for specific category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b | Genotype 1a | 27.3 Percentage of Participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b | Genotype 1b | 33.3 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b | Genotype 1a | 54.5 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b | Genotype 1b | 66.7 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype)
Percentage of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported.
Time frame: Post-treatment Week 12
Population: All included treated participants. Here, n' signifies number of participants analysed for specific category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype) | CC genotype | 40.0 Percentage of Participants |
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype) | Non-CC Genotype | 22.2 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype) | CC genotype | 66.7 Percentage of Participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype) | Non-CC Genotype | 50.0 Percentage of Participants |
Secondary
Percentage of Participants With End of Treatment Response (EOTR)
EOTR was defined as HCV RNA less than the lower limit of quantitation, target detected or not detected at end of treatment.
Time frame: End of the treatment
Population: All treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 4 Weeks DCV 3DAA + SOF | Percentage of Participants With End of Treatment Response (EOTR) | 92.9 Percentage of participants |
| 6 Weeks DCV 3DAA + SOF | Percentage of Participants With End of Treatment Response (EOTR) | 100.0 Percentage of participants |