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Phase III Daclatasvir and Sofosbuvir for Genotype 3 Chronic HCV (ALLY 3)

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ClinicalTrials.gov Identifier: NCT02032901
Recruitment Status : Completed
First Posted : January 10, 2014
Results First Posted : September 14, 2015
Last Update Posted : October 1, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C
Interventions Drug: Daclatasvir
Drug: Sofosbuvir
Enrollment 173
Recruitment Details The study was conducted at 31 sites in 2 countries.
Pre-assignment Details A total of 173 participants were enrolled in the study. 152 were treated. 21 participants were not treated as they no longer met the study criteria.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks. Participants infected with hepatitis C virus (HCV) genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg tablets and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Period Title: Treatment Period (12 Weeks)
Started 101 51
Completed 100 51
Not Completed 1 0
Reason Not Completed
Pregnancy             1             0
Period Title: Follow-Up Period (24 Weeks)
Started 101 [1] 51
Completed 101 50
Not Completed 0 1
Reason Not Completed
Lost to Follow-up             0             1
[1]
Participant could enter follow up period even if the treatment period was not completed.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants Total
Hide Arm/Group Description Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks. Participants infected with hepatitis C virus (HCV) genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 101 51 152
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 51 participants 152 participants
50.3  (10.73) 56.3  (6.64) 52.3  (9.94)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 101 participants 51 participants 152 participants
<65 years 95 47 142
>= 65 years 6 4 10
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 51 participants 152 participants
Female
43
  42.6%
19
  37.3%
62
  40.8%
Male
58
  57.4%
32
  62.7%
90
  59.2%
1.Primary Outcome
Title Percentage of Treatment-Naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) Target Detected (TD) or Target Not Detected (TND)
Hide Description SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation ie., 25 IU/mL, TD or TND at follow-up Week 12. HCV RNA levels were measured by the Roche Cobas® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Week 12 (Follow-up period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants
Hide Arm/Group Description:
Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 101
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
90.1
(82.5 to 95.1)
2.Primary Outcome
Title Percentage of Treatment-Experienced Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) Target Detected (TD) or Target Not Detected (TND)
Hide Description SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation ie., 25 IU/mL, 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.
Time Frame Week 12 (Follow-up period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description:
Participants infected with HCV genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
86.3
(73.7 to 94.3)
3.Secondary Outcome
Title Percentage of Participants With Rapid Virologic Response at Week 4 (RVR) Target Not Detected (TND)
Hide Description RVR was defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 25 IU/mL TND at Week 4. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description:
Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Participants infected with hepatitis C virus (HCV) genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg tablets and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 101 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
63.4
(53.2 to 72.7)
72.5
(58.3 to 84.1)
4.Secondary Outcome
Title Percentage of Participants With Complete Early Virologic Response (cEVR) Target Not Detected (TND)
Hide Description cEVR was defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 25 IU/mL TND at Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description:
Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Participants infected with hepatitis C virus (HCV) genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 101 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
98.0
(93.0 to 99.8)
100.0
(93.0 to 100.0)
5.Secondary Outcome
Title Percentage of Participants With End of Treatment Response (EOTR) Target Not Detected (TND)
Hide Description EOTR were defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 25 IU/mL TND at end of treatment. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Up to the end of treatment (up to 24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description:
Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Participants infected with HCV genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg tablets and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 101 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
99.0
(94.6 to 100.0)
100.0
(93.0 to 100.0)
6.Secondary Outcome
Title Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Less Than the Lower Limit of Quantitation (LLOQ) - Target Not Detected (TND)
Hide Description Percentage of participants who achieved HCV RNA <LLOQ, TND was determined (LLOQ: 25 IU/mL). HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Week 1, 2, 6, 8 (treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description:
Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Participants infected with hepatitis C virus (HCV) genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg tablets and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 101 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 1
11.9
(6.3 to 19.8)
2.0
(0.0 to 10.4)
Week 2
34.7
(25.5 to 44.8)
29.4
(17.5 to 43.8)
Week 6
86.1
(77.8 to 92.2)
90.2
(78.6 to 96.7)
Week 8
95.0
(88.8 to 98.4)
98.0
(89.6 to 100.0)
7.Secondary Outcome
Title Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Less Than the Lower Limit of Quantitation (LLOQ)- Target Detected (TD) or Target Not Detected (TND)
Hide Description Percentage of participants who achieved HCV RNA <LLOQ,TD or TND was determined (LLOQ: 25 IU/mL). HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Week 1, 2, 4, 6, 8, 12, End of treatment (treatment period), Week 4 (follow-up period), Week 24 (follow-up period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description:
Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Participants infected with hepatitis C virus (HCV) genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg tablets and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 101 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 1
39.6
(30.0 to 49.8)
23.5
(12.8 to 37.5)
Week 2
77.2
(67.8 to 85.0)
68.6
(54.1 to 80.9)
Week 4
94.1
(87.5 to 97.8)
98.0
(89.6 to 100.0)
Week 6
100.0
(96.4 to 100.0)
98.0
(89.6 to 100.0)
Week 8
100.0
(96.4 to 100.0)
100.0
(93.0 to 100.0)
Week 12
98.0
(93.0 to 99.8)
100.0
(93.0 to 100.0)
End of treatment
99.0
(94.6 to 100.0)
100.0
(93.0 to 100.0)
Follow-up Week 4
91.1
(83.8 to 95.8)
86.3
(73.7 to 94.3)
Follow-up Week 24
89.1
(81.3 to 94.4)
82.4
(69.1 to 91.6)
8.Secondary Outcome
Title Percentage of Participants With Or Without Cirrhosis at Baseline Who Achieved Sustained Virologic Response at Follow-up Week 12 (SVR12)
Hide Description SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation ie. 25 IU/mL, target detected or target not detected at follow-up Week 12. Cirrhosis was considered a negative predictor of SVR in participants treated with an interferon formulation or ribavirin. Presence or absence of cirrhosis was determined at baseline and follow-up Week 12 in the participants to evaluate the post-treatment relapse.
Time Frame Baseline, Week 12 (Follow-up period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy. The 'n' signifies the number of evaluable participants with or without cirrhosis in the reporting arm and time point, respectively.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description:
Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Participants infected with hepatitis C virus (HCV) genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg tablets and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 101 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
With cirrhosis (n= 19, 13)
57.9
(33.5 to 79.7)
69.2
(38.6 to 90.9)
Without cirrhosis (n= 75, 34)
97.3
(90.7 to 99.7)
94.1
(80.3 to 99.3)
9.Secondary Outcome
Title Percentage of Participants With CC or Non-CC Genotype at the IL28B rs12979860 Single Nucleotide Polymorphisms (SNPs) Who Achieved Sustained Virologic Response After 12 Weeks of Follow-up (SVR12)
Hide Description Participants categorized into 2 genotypes (CC and non-CC) based on SNPs in the IL28B gene were assessed for SVR12, defined as response in which hepatitis C virus (HCV) RNA levels below lower limit of quantitation (LLOQ) below target detected or target not detected at follow-up Week 12 (LLOQ: 25 IU/mL). HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Week 12 (Follow-up period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, ''n'' signifies number of participants evaluable for the specified category.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description:
Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Participants infected with hepatitis C virus (HCV) genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg tablets and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 101 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Genotype: CC (n=40, 20)
90.0
(76.3 to 97.2)
95.0
(75.1 to 99.9)
Genotype: Non-CC (n=61, 31)
90.2
(79.8 to 96.3)
80.6
(62.5 to 92.5)
10.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)
Hide Description AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily 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 Day 1 first dose to last dose plus 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in all treated participants who received at least 1 dose of active study therapy.
Arm/Group Title Daclatasvir + Sofosbuvir in Treatment-naive Participants Daclatasvir + Sofosbuvir in Treatment-experienced Participants
Hide Arm/Group Description:
Participants infected with hepatitis C virus (HCV) genotype-3 and not exposed to an interferon formulation or ribavirin or any other HCV-specific direct-acting antiviral therapy, received daclatasvir 60-mg and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Participants infected with hepatitis C virus (HCV) genotype-3 and previously exposed to an interferon formulation or sofosbuvir /ribavirin or any other anti-HCV agents therapy, received daclatasvir 60-mg tablets and sofosbuvir 400-mg tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 101 51
Measure Type: Number
Unit of Measure: Participants
SAEs 1 0
Discontinuations Due to AEs 0 0
Time Frame From Day 1 first dose to last dose plus 7 days
Adverse Event Reporting Description On-treatment period.
 
Arm/Group Title Daclatasvir + Sofosbuvir
Hide Arm/Group Description All participants infected with hepatitis C virus (HCV) genotype-3 received daclatasvir 60-mg tablets and sofosbuvir 400-mg tablets orally once daily for 12 weeks during the study.
All-Cause Mortality
Daclatasvir + Sofosbuvir
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Daclatasvir + Sofosbuvir
Affected / at Risk (%)
Total   1/152 (0.66%) 
Gastrointestinal disorders   
Gastrointestinal haemorrhage  1  1/152 (0.66%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Daclatasvir + Sofosbuvir
Affected / at Risk (%)
Total   73/152 (48.03%) 
Gastrointestinal disorders   
Abdominal pain  1  8/152 (5.26%) 
Diarrhoea  1  13/152 (8.55%) 
Nausea  1  18/152 (11.84%) 
General disorders   
Fatigue  1  29/152 (19.08%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  8/152 (5.26%) 
Nervous system disorders   
Headache  1  30/152 (19.74%) 
Psychiatric disorders   
Insomnia  1  9/152 (5.92%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
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
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02032901     History of Changes
Other Study ID Numbers: AI444-218
First Submitted: January 9, 2014
First Posted: January 10, 2014
Results First Submitted: August 12, 2015
Results First Posted: September 14, 2015
Last Update Posted: October 1, 2015