Trial Outcomes & Findings for Safety and Efficacy Study of the Combination Daclatasvir (60 mg), Sofosbuvir (400 mg) and Ribavirin (Weight-based Dosing) for 12 or 16 Weeks in Subjects With Genotype 3 Chronic HCV Infection With or Without Prior Treatment Experience and Advanced Fibrosis or Compensated Cirrhosis (NCT NCT02319031)

NCT ID: NCT02319031

Last Updated: 2017-01-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

53 participants

Primary outcome timeframe

Follow-up Week 12

Results posted on

2017-01-27

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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	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
Treatment Period STARTED	24	26
Treatment Period COMPLETED	23	26
Treatment Period NOT COMPLETED	1	0
Follow-Up Period STARTED	23	26
Follow-Up Period COMPLETED	23	26
Follow-Up Period NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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
Treatment Period Death	1	0

Baseline Characteristics

Safety and Efficacy Study of the Combination Daclatasvir (60 mg), Sofosbuvir (400 mg) and Ribavirin (Weight-based Dosing) for 12 or 16 Weeks in Subjects With Genotype 3 Chronic HCV Infection With or Without Prior Treatment Experience and Advanced Fibrosis or Compensated Cirrhosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) n=24 Participants 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	Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) n=26 Participants 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	Total n=50 Participants Total of all reporting groups
Age, Continuous	53.0 years STANDARD_DEVIATION 7.77 • n=5 Participants	55.0 years STANDARD_DEVIATION 5.75 • n=7 Participants	54.1 years STANDARD_DEVIATION 6.80 • n=5 Participants
Age, Customized <65	23 participants n=5 Participants	26 participants n=7 Participants	49 participants n=5 Participants
Age, Customized >=65	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Gender Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Gender Male	18 Participants n=5 Participants	22 Participants n=7 Participants	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: Follow-up Week 12

Population: All treated participants: Enrolled participants who received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) n=24 Participants 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	Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) n=26 Participants 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
Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 12 (SVR12)	87.5 percentage of participants Interval 67.6 to 97.3	92.3 percentage of participants Interval 74.9 to 99.1

SECONDARY outcome

Timeframe: Follow-up Weeks 4 and 24

Population: All treated participants: Enrolled participants who received at least 1 dose of study drug

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.

Outcome measures

Outcome measures
Measure	Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) n=24 Participants 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	Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) n=26 Participants 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
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 Interval 67.6 to 97.3	96.2 percentage of participants Interval 80.4 to 99.9
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 Interval 67.6 to 97.3	92.3 percentage of participants Interval 74.9 to 99.1

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) n=24 Participants 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	Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) n=26 Participants 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
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	0 participants
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	0 participants
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	2 participants
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	2 participants
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	3 participants

Adverse Events

Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks)

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks)

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks) n=24 participants at risk 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	Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks) n=26 participants at risk 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
Vascular disorders Arteriosclerosis	0.00% 0/24 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015	3.8% 1/26 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015
Infections and infestations Pneumonia	0.00% 0/24 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015	3.8% 1/26 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/24 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015	3.8% 1/26 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015
Nervous system disorders Somnolence	4.2% 1/24 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015	0.00% 0/26 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015
Cardiac disorders Congestive cardiomyopathy	4.2% 1/24 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015	0.00% 0/26 • SAEs were reported from date of first dose of study drug to 30 days post discontinuation of the last dose which was up to 16 weeks or 20 weeks depending on the randomized treatment group. Non-serious AEs were reported from date of first dose of study drug to 7 days post discontinuation of the last dose which was up to 13 weeks or 17 weeks depending on the randomized treatment group. Study initiated February 2015; study completed December 2015

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER