ALLY 1: Phase III Daclatasvir, Sofosbuvir, and Ribavirin in Cirrhotic Participants and Participants Post-liver Transplant
Study Details
Study Description
Brief Summary
This trial was open to participants who had received a liver transplant or had cirrhosis due to chronic HCV. All subjects were treated with daclatasvir+sofosbuvir+ribavirin and were followed for 24 weeks post treatment. Under certain conditions, the treatment duration could have been extended for cirrhotic participants. The study tested the efficacy and safety of this combination for treatment of HCV in cirrhotic and post transplant patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Post-liver Transplant Cohort Participants with liver transplant received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets daily for 12 weeks and were followed for 24 weeks post treatment. |
Drug: Daclatasvir
Other Names:
Drug: Sofosbuvir
Drug: Ribavirin
|
| Experimental: Cirrhotic Cohort Cirrhotic participants received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets orally for 12 weeks and were followed for 24 weeks post-treatment. Cirrhotic participants who received a liver transplant while on study treatment were eligible (>3 months post transplant) for a treatment extension of daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (dose based on hemoglobin level) tablets orally for an additional 12 weeks |
Drug: Daclatasvir
Other Names:
Drug: Sofosbuvir
Drug: Ribavirin
|
Outcome Measures
Primary Outcome Measures
- Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) [Post-treatment follow-up Week 12]
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation (<LLOQ) i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
- Percentage of Genotype-1 Infected Cirrhotic Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) [Post-treatment follow-up Week 12]
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Secondary Outcome Measures
- Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 [Post-treatment follow-up Week 12]
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
- Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 [Week 1, 2, 4, 6, 8, 12, End of treatment, Follow-up Week 4, 8, and 24]
Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at each visit.
- Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment [Week 1, 2, 4, 6, 8, 12, End of treatment]
Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target not detected, at each on-treatment visit.
- Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12) [Post-treatment follow-up Week 12]
Participants categorized into 2 genotypes (CC and non-CC) based on single nucleotide polymorphism in the IL28B gene were assessed for SVR12, defined as response in which hepatitis C virus RNA levels be <lower limit of quantitation ie, 25 IU/mL or below target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
- Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death [From start of study treatment up to 7 days post last dose of study treatment (approximately 13 weeks)]
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.
- Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities [From start of study treatment up to 7 days post last dose of study treatment]
Grade 3-4 laboratory abnormalities were defined as: Hemoglobin as 6.50-7.4 g/dL for grade 3 and/or < 6.5 g/dL for grade 4, Platelet count as 25*10^9-50*10^9 /L for grade 3 and/or < 25.000*10^9 /L for grade 4, International normalized ratio as 2.1-3.0*upper limit of normal (ULN) > 3.0*ULN for grade 3 and/or > 3.0*ULN for grade 4, Leukocytes as 1.0*10^9-1.5*10^9/L for grade 3 and/or <1.0*10^9/L for grade 4, Lymphocytes (Absolute) as 0.350*109-0.499*10^9 /L for grade 3 and/or < 0.350*10^9 /L for grade 4, Alanine aminotransferase as 5.1-10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Aspartate aminotransferase as 5.1-10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Alkaline phosphatase as 5.1-10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Bilirubin (Total) as 2.6-5.0*ULN for grade 3 and/or > 5.0*ULN for grade 4, Albumin as < 20 g/L, Lipase (Total) as 3.1-5.0*ULN for grade 3 and/or > 5.0*ULN for grade 4, and Creatinine as 1.9-3.4*ULN for grade 3 and/or ≥ 3.5*ULN for grade 4.
Eligibility Criteria
Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria:
-
Participants must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications
-
Participants chronically infected with hepatitis C virus (HCV) Genotype 1, 2, 3, 4, 5, or 6 with HCV RNA viral load of ≥10,000 IU/mL at screening
-
Participants may be treatment-naïve or treatment-experienced
-
Cirrhotic participants must have cirrhosis confirmed by biopsy, Fibroscan or fibrotest and Aspartate aminotransferase platelet ratio index (APRI) criteria as outlined in the protocol
-
Post-transplant participants must be at least 3 months post-transplant with no evidence of moderate or severe rejection
Exclusion Criteria:
-
History of multi-organ transplant, with the exception of dual transplantation of the liver/kidney, is prohibited
-
Current or known history of cancer (with the following exceptions: In situ carcinoma of the cervix, adequately treated basal or squamous cell carcinoma of the skin, or hepatocellular carcinoma within Milan criteria for transplantation) within 5 years prior to screening
-
Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, or toxin exposures)
-
History of HIV infection or chronic hepatitis B virus (HBV) as documented by HBV serologies (e.g., HBsAg-seropositive). Participants with resolved HBV infection may participate (e.g., HBcAb-seropositive with concurrent HBsAg-seronegative)
-
Active hospitalization for decompensated liver disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Of Miami Schiff Center For Liver Diseases | Miami | Florida | United States | 33136 |
| 2 | University Of Michigan Health System | Ann Arbor | Michigan | United States | 48109 |
| 3 | Baylor St. Luke'S Medical Center | Houston | Texas | United States | 77030 |
| 4 | American Research Corporation | San Antonio | Texas | United States | 78215 |
| 5 | Harborview Medical Center | Seattle | Washington | United States | 98104 |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- AI444-215
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 5 centers in the United States. |
|---|---|
| Pre-assignment Detail | A total of 116 participants were enrolled, of which 113 received study treatment (60 cirrhotic cohort, 53: post-liver transplant cohort). Remaining 3 participants no longer met study criteria. Of the 60 participants in the cirrhotic cohort, 57 did not receive a treatment extension and 3 received a treatment extension after liver transplant. |
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin |
|---|---|---|
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. |
| Period Title: Treatment Period | ||
| STARTED | 53 | 60 |
| COMPLETED | 52 | 56 |
| NOT COMPLETED | 1 | 4 |
| Period Title: Treatment Period | ||
| STARTED | 53 | 57 |
| COMPLETED | 50 | 46 |
| NOT COMPLETED | 3 | 11 |
Baseline Characteristics
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Total |
|---|---|---|---|
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Total of all reporting groups |
| Overall Participants | 53 | 60 | 113 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
59.6
(8.25)
|
57.9
(9.45)
|
58.7
(8.91)
|
| Age, Customized (participants) [Number] | |||
| <65 years |
42
79.2%
|
50
83.3%
|
92
81.4%
|
| >=65 years |
11
20.8%
|
10
16.7%
|
21
18.6%
|
| Gender (Count of Participants) | |||
| Female |
15
28.3%
|
22
36.7%
|
37
32.7%
|
| Male |
38
71.7%
|
38
63.3%
|
76
67.3%
|
| Hepatitis C Virus RNA (log10 IU/mL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [log10 IU/mL] |
6.61
(0.711)
|
6.01
(0.617)
|
6.29
(0.724)
|
| Hepatitis C Virus RNA distribution (participants) [Number] | |||
| <800,000 IU/mL |
6
11.3%
|
27
45%
|
33
29.2%
|
| ≥800,000 IU/mL |
47
88.7%
|
33
55%
|
80
70.8%
|
| HCV genotype subtype (participants) [Number] | |||
| Hepatitis C Virus genotype 1a |
31
58.5%
|
34
56.7%
|
65
57.5%
|
| Hepatitis C Virus genotype 1b |
10
18.9%
|
11
18.3%
|
21
18.6%
|
| Hepatitis C Virus genotype 2 |
0
0%
|
5
8.3%
|
5
4.4%
|
| Hepatitis C Virus genotype 3 |
11
20.8%
|
6
10%
|
17
15%
|
| Hepatitis C Virus genotype 4 |
0
0%
|
4
6.7%
|
4
3.5%
|
| Hepatitis C Virus genotype 5 |
0
0%
|
0
0%
|
0
0%
|
| Hepatitis C Virus genotype 6 |
1
1.9%
|
0
0%
|
1
0.9%
|
| IL-28B rs1297860 Genotype (participants) [Number] | |||
| CC |
13
24.5%
|
13
21.7%
|
26
23%
|
| CT |
31
58.5%
|
33
55%
|
64
56.6%
|
| TT |
9
17%
|
14
23.3%
|
23
20.4%
|
Outcome Measures
| Title | Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) |
|---|---|
| Description | SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation (<LLOQ) i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. |
| Time Frame | Post-treatment follow-up Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All HCV genotype 1 infected post-transplant participants who received at least 1 dose of study therapy. |
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin |
|---|---|
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. |
| Measure Participants | 41 |
| Number (95% Confidence Interval) [Percentage of participants] |
95.1
179.4%
|
| Title | Percentage of Genotype-1 Infected Cirrhotic Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) |
|---|---|
| Description | SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. |
| Time Frame | Post-treatment follow-up Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All genotype 1 cirrhotic participants who received at least 1 dose of study therapy. |
| Arm/Group Title | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin |
|---|---|
| Arm/Group Description | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. |
| Measure Participants | 45 |
| Number (95% Confidence Interval) [Percentage of participants] |
82.2
155.1%
|
| Title | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 |
|---|---|
| Description | SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. |
| Time Frame | Post-treatment follow-up Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants who took at least 1 dose of study medication. Here, 'n' signifies participants evaluable for SVR12 at the specified time point in each group, respectively. |
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin |
|---|---|---|
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. |
| Measure Participants | 53 | 60 |
| All Genotypes (n =53, 60) |
94.3
177.9%
|
83.3
138.8%
|
| HCV Genotype 2 (n =0, 5) |
NA
NaN
|
80
133.3%
|
| HCV Genotype 3 (n =11, 6) |
90.9
171.5%
|
83.3
138.8%
|
| HCV Genotype 4 (n =0, 4) |
NA
NaN
|
100
166.7%
|
| HCV Genotype 6 (n =1, 0) |
100
188.7%
|
NA
NaN
|
| Title | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 |
|---|---|
| Description | Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at each visit. |
| Time Frame | Week 1, 2, 4, 6, 8, 12, End of treatment, Follow-up Week 4, 8, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin |
|---|---|---|
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. |
| Measure Participants | 53 | 60 |
| Week 1 |
22.6
42.6%
|
15.0
25%
|
| Week 2 |
67.9
128.1%
|
45.0
75%
|
| Week 4 |
94.3
177.9%
|
95.0
158.3%
|
| Week 6 |
96.2
181.5%
|
91.7
152.8%
|
| Week 8 |
98.1
185.1%
|
95.0
158.3%
|
| Week 12 |
98.1
185.1%
|
93.3
155.5%
|
| End of treatment |
100.0
188.7%
|
96.7
161.2%
|
| Follow-up Week 4 (SVR4) |
98.1
185.1%
|
88.3
147.2%
|
| Follow-up Week 8 (SVR8) |
96.2
181.5%
|
86.7
144.5%
|
| Follow-up Week 24 (SVR24) |
94.3
177.9%
|
80.0
133.3%
|
| Title | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment |
|---|---|
| Description | Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target not detected, at each on-treatment visit. |
| Time Frame | Week 1, 2, 4, 6, 8, 12, End of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin |
|---|---|---|
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. |
| Measure Participants | 53 | 60 |
| Week 1 |
3.8
7.2%
|
1.7
2.8%
|
| Week 2 |
13.2
24.9%
|
11.7
19.5%
|
| Week 4 |
56.6
106.8%
|
53.3
88.8%
|
| Week 6 |
84.9
160.2%
|
76.7
127.8%
|
| Week 8 |
98.1
185.1%
|
93.3
155.5%
|
| Week 12 |
98.1
185.1%
|
93.3
155.5%
|
| End of treatment |
100.0
188.7%
|
96.7
161.2%
|
| Title | Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12) |
|---|---|
| Description | Participants categorized into 2 genotypes (CC and non-CC) based on single nucleotide polymorphism in the IL28B gene were assessed for SVR12, defined as response in which hepatitis C virus RNA levels be <lower limit of quantitation ie, 25 IU/mL or below target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. |
| Time Frame | Post-treatment follow-up Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. Here, 'n' signifies participants evaluable for SVR12 at the specified time point in each group, respectively. |
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin |
|---|---|---|
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. |
| Measure Participants | 53 | 60 |
| CC type (n = 13, 13) |
100
188.7%
|
84.6
141%
|
| Non-CC type (n = 40, 47) |
92.5
174.5%
|
78.7
131.2%
|
| Title | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death |
|---|---|
| Description | AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. |
| Time Frame | From start of study treatment up to 7 days post last dose of study treatment (approximately 13 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin |
|---|---|---|
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. |
| Measure Participants | 53 | 60 |
| SAEs |
5
9.4%
|
10
16.7%
|
| AEs leading to discontinuation |
6
11.3%
|
10
16.7%
|
| AEs leading to interruption |
1
1.9%
|
3
5%
|
| Treatment-related AEs |
35
66%
|
37
61.7%
|
| Treatment-related SAEs |
0
0%
|
0
0%
|
| Adverse events Grade 3 to 4 |
5
9.4%
|
11
18.3%
|
| Serious adverse events Grade 3 to 4 |
2
3.8%
|
8
13.3%
|
| Death |
0
0%
|
0
0%
|
| Title | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities |
|---|---|
| Description | Grade 3-4 laboratory abnormalities were defined as: Hemoglobin as 6.50-7.4 g/dL for grade 3 and/or < 6.5 g/dL for grade 4, Platelet count as 25*10^9-50*10^9 /L for grade 3 and/or < 25.000*10^9 /L for grade 4, International normalized ratio as 2.1-3.0*upper limit of normal (ULN) > 3.0*ULN for grade 3 and/or > 3.0*ULN for grade 4, Leukocytes as 1.0*10^9-1.5*10^9/L for grade 3 and/or <1.0*10^9/L for grade 4, Lymphocytes (Absolute) as 0.350*109-0.499*10^9 /L for grade 3 and/or < 0.350*10^9 /L for grade 4, Alanine aminotransferase as 5.1-10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Aspartate aminotransferase as 5.1-10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Alkaline phosphatase as 5.1-10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Bilirubin (Total) as 2.6-5.0*ULN for grade 3 and/or > 5.0*ULN for grade 4, Albumin as < 20 g/L, Lipase (Total) as 3.1-5.0*ULN for grade 3 and/or > 5.0*ULN for grade 4, and Creatinine as 1.9-3.4*ULN for grade 3 and/or ≥ 3.5*ULN for grade 4. |
| Time Frame | From start of study treatment up to 7 days post last dose of study treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin |
|---|---|---|
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. |
| Measure Participants | 53 | 60 |
| Hemoglobin |
2
3.8%
|
5
8.3%
|
| Platelet count |
0
0%
|
4
6.7%
|
| International normalized ratio |
0
0%
|
1
1.7%
|
| Leukocytes |
2
3.8%
|
0
0%
|
| Lymphocytes (Absolute) |
3
5.7%
|
6
10%
|
| Alanine aminotransferase |
0
0%
|
2
3.3%
|
| Aspartate aminotransferase |
0
0%
|
3
5%
|
| Alkaline phosphatase |
1
1.9%
|
0
0%
|
| Bilirubin (Total) |
2
3.8%
|
9
15%
|
| Albumin |
0
0%
|
1
1.7%
|
| Lipase (Total) |
2
3.8%
|
3
5%
|
| Creatinine |
2
3.8%
|
2
3.3%
|
Adverse Events
| Time Frame | From Day 1 up to 7 days post last dose of study treatment (approximately 13 weeks) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Study Start: March 17, 2014; Study Completion: January 5, 2016 | |||
| Arm/Group Title | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | ||
| Arm/Group Description | Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | ||
All Cause Mortality |
||||
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/53 (9.4%) | 10/60 (16.7%) | ||
| Gastrointestinal disorders | ||||
| Haematemesis | 0/53 (0%) | 1/60 (1.7%) | ||
| Ascites | 0/53 (0%) | 1/60 (1.7%) | ||
| Haemorrhoidal haemorrhage | 0/53 (0%) | 1/60 (1.7%) | ||
| Abdominal pain | 0/53 (0%) | 1/60 (1.7%) | ||
| Localised intraabdominal fluid collection | 1/53 (1.9%) | 0/60 (0%) | ||
| Hepatobiliary disorders | ||||
| Hepatic cirrhosis | 0/53 (0%) | 1/60 (1.7%) | ||
| Infections and infestations | ||||
| Clostridium difficile infection | 0/53 (0%) | 1/60 (1.7%) | ||
| Upper respiratory tract infection | 1/53 (1.9%) | 0/60 (0%) | ||
| Cellulitis | 0/53 (0%) | 1/60 (1.7%) | ||
| Metabolism and nutrition disorders | ||||
| Hyponatraemia | 0/53 (0%) | 1/60 (1.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Polyarthritis | 1/53 (1.9%) | 0/60 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Breast cancer | 0/53 (0%) | 1/60 (1.7%) | ||
| Hepatocellular carcinoma | 0/53 (0%) | 3/60 (5%) | ||
| Nervous system disorders | ||||
| Encephalopathy | 0/53 (0%) | 1/60 (1.7%) | ||
| Hepatic encephalopathy | 1/53 (1.9%) | 1/60 (1.7%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/53 (1.9%) | 0/60 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/53 (71.7%) | 42/60 (70%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 11/53 (20.8%) | 13/60 (21.7%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 10/53 (18.9%) | 5/60 (8.3%) | ||
| Abdominal pain | 3/53 (5.7%) | 2/60 (3.3%) | ||
| Nausea | 3/53 (5.7%) | 10/60 (16.7%) | ||
| General disorders | ||||
| Fatigue | 15/53 (28.3%) | 11/60 (18.3%) | ||
| Oedema peripheral | 4/53 (7.5%) | 4/60 (6.7%) | ||
| Pyrexia | 3/53 (5.7%) | 3/60 (5%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 3/53 (5.7%) | 2/60 (3.3%) | ||
| Upper respiratory tract infection | 3/53 (5.7%) | 1/60 (1.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 7/53 (13.2%) | 1/60 (1.7%) | ||
| Back pain | 1/53 (1.9%) | 3/60 (5%) | ||
| Nervous system disorders | ||||
| Somnolence | 0/53 (0%) | 3/60 (5%) | ||
| Headache | 19/53 (35.8%) | 9/60 (15%) | ||
| Dizziness | 4/53 (7.5%) | 1/60 (1.7%) | ||
| Psychiatric disorders | ||||
| Insomnia | 4/53 (7.5%) | 3/60 (5%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 1/53 (1.9%) | 5/60 (8.3%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
- AI444-215