MAGNITUDE: Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01741545
• Collaborator: (none)
• Enrollment: 71
• Locations: 32
• Arms: 2
• Actual Duration (Months): 22
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective for this study is to evaluate the proportion of subjects who achieve SVR12 (HCV RNA < LLOQ (target not detected) at post-treatment follow-up Week 12 in subjects with Genotype(GT)-1b, -4 and GT-2, -3

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus	Biological: Pegylated-Interferon-lambda; Drug: Ribavirin; Drug: Daclatasvir	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study Evaluating the Safety and Efficacy of Lambda/Ribavirin/Daclatasvir in Subjects With Chronic HCV Infection and Underlying Hemophilia Who Are Treatment Naïve or Are Prior Relapsers to Peginterferon Alfa-2a/Ribavirin
• Actual Study Start Date: Mar 31, 2013
• Actual Primary Completion Date: Jan 31, 2015
• Actual Study Completion Date: Jan 31, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: Genotype-2,-3 (Lambda/RBV/DCV) Lambda 180 μg solution for subcutaneous (SC) injection, once weekly for 12 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 12 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks	Biological: Pegylated-Interferon-lambda; Other Names: pegIFNλ BMS-914143 ; Drug: Ribavirin; Drug: Daclatasvir; Other Names: BMS-790052
Experimental: Cohort B: Genotype-1b,-4 (Lambda/RBV/DCV) Lambda 180 μg solution for subcutaneous (SC) injection, once weekly for 24 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 24 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks	Biological: Pegylated-Interferon-lambda; Other Names: pegIFNλ BMS-914143 ; Drug: Ribavirin; Drug: Daclatasvir; Other Names: BMS-790052

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12 [Follow-up Week 12]

   SVR12 was defined as HCV ribonucleic acid (RNA) less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12.

Secondary Outcome Measures

1. Percentage of Participants With Rapid Virologic Response (RVR) [Treatment Week 4]

   RVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 4.

2. Percentage of Participants With Complete Early Virologic Response (cEVR) [Treatment Week 12]

   cEVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 12.

3. Percentage of Participants With End of the Treatment Response (EOTR) [End of the treatment (Week 12 for Cohort A, Week 24 for Cohort B)]

   EOTR was defined as HCV RNA less than the lower limit of quantitation, target not detected at end of treatment.

4. Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24) [Follow-up Week 24]

   SVR24 was defined as HCV RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24.

5. Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment [After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)]

   Cytopenic abnormalities were defined as anemia: Hemoglobin (Hb) <10 g/dL, and/or neutropenia: absolute neutrophils and bands (ANC) <750 mm^3, and/or thrombocytopenia: platelets <50,000 mm^3.

6. Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment [After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)]

   Flu-like symptoms were defined as pyrexia or chills or pain. Musculoskeletal symptoms were defined as arthralgia or myalgia or back pain.

7. Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death [From Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B)]

   AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug.

8. Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities [After day 1 to to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)]

   Laboratory abnormalities were determined and graded using the Division of acquired immunodeficiency syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, version 1.0. International Normalized Ratio (INR): >2.0*Upper limit of normal (ULN); Alanine aminotransferase (ALT) : >5*ULN; Aspartate aminotransferase (AST): >5*ULN; Prothrombin Time (PT): >1.50*ULN; Bilirubin (Total): >2.5*ULN; Triglycerides (fasting): >750 mg/dL.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

• Severe hemophilia (defined as < 1% factor activity level)

• Infection with the hepatitis C virus (HCV) with underlying hemophilia

• Males 18 years of age and above

• Have not been previously treated with an interferon

Exclusion Criteria:

• Not infected with the hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

• Chronic liver disease caused by any disease other than chronic HCV infection

• Presence of Bethesda inhibitor

• Current evidence of or history of portal hypertension

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Boswell Clinic	Palo Alto	California	United States	94304
2	Rush University Medical Center	Chicago	Illinois	United States	60612
3	Hospital Of The University Of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
4	Clinical Research Centers Of America	Murray	Utah	United States	84123
5	Local Institution	Camperdown	New South Wales	Australia	2050
6	Local Institution	Herston	Queensland	Australia	4029
7	Local Institution	Adelaide	South Australia	Australia	5000
8	Local Institution	Melbourne	Victoria	Australia	3004
9	Local Institution	Herston		Australia	4029
10	Local Institution	Grenoble		France	38043
11	Local Institution	Lyon Cedex 04		France	69317
12	Local Institution	Montpellier Cedex 5		France	34295
13	Local Institution	Paris Cedex 13		France	75651
14	Local Institution	Paris Cedex 14		France	75679
15	Local Institution	Vandoeuvre Les Nancy		France	54511
16	Local Institution	Firenze		Italy	50134
17	Local Institution	Milan		Italy	20122
18	Local Institution	Roma		Italy	00185
19	Local Institution	Torino		Italy	10126
20	Local Institution	Amsterdam		Netherlands	1105 AZ
21	Local Institution	Nijmegen		Netherlands	6525 GA
22	Local Institution	Rotterdam		Netherlands	3015 CE
23	Local Institution	Utrecht		Netherlands	3508 GA
24	Local Institution	Bucuresti		Romania	50524
25	Local Institution	Constanta		Romania	900635
26	Local Institution	Iasi		Romania	700116
27	Local Institution	Iasi		Romania	700506
28	Local Institution	Moscow		Russian Federation	107996
29	Local Institution	Saint Petersburg		Russian Federation	191186
30	Local Institution	Barcelona		Spain	08035
31	Local Institution	Madrid		Spain	28046
32	Local Institution	Sevilla		Spain	41013

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:

• BMS clinical trial educational resource

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01741545
• Other Study ID Numbers: AI452-030; 2012-003463-22
• First Posted: Dec 5, 2012
• Last Update Posted: Aug 11, 2020
• Last Verified: Aug 1, 2020

• Additional relevant MeSH terms: Hepatitis C; Interferons; Ribavirin

Study Results

Participant Flow

Pre-assignment Detail	A total of 71 participants were enrolled, of which 51 subjects were randomized and treated.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with hepatitis C virus (HCV) genotype (GT)-2 or GT-3 infection (Cohort A) were treated with peginterferon lambda-1a (pegIFNλ-1a referred to as Lambda)/Ribavirin (RBV)/Daclatasvir (DCV). Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Period Title: Treatment Period
STARTED	12	39
COMPLETED	11	35
NOT COMPLETED	1	4
Period Title: Treatment Period
STARTED	12	39
COMPLETED	11	37
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Cohort A	Cohort B	Total
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Total of all reporting groups
Overall Participants	12	39	51
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	38 97.4%	50 98%
>=65 years	0 0%	1 2.6%	1 2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.8 (9.94)	45.2 (12.04)	44.6 (11.53)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	12 100%	39 100%	51 100%
HCV Genotype (Count of Participants)
Genotype 1A	0 0%	0 0%	0 0%
Genotype 1B	0 0%	39 100%	39 76.5%
Genotype 2	2 16.7%	0 0%	2 3.9%
Genotype 3	10 83.3%	0 0%	10 19.6%
Genotype 4	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12
Description	SVR12 was defined as HCV ribonucleic acid (RNA) less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12.
Time Frame	Follow-up Week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed in modified intent to treat (mITT) population defined as participants meeting the response criteria over all treated participants.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Measure Participants	12	39
Number (95% Confidence Interval) [Percentage of participants]	91.7 764.2%	89.7 230%

2. Secondary Outcome

Title	Percentage of Participants With Rapid Virologic Response (RVR)
Description	RVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 4.
Time Frame	Treatment Week 4

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Measure Participants	12	39
Number (95% Confidence Interval) [Percentage of participants]	91.7 764.2%	76.9 197.2%

3. Secondary Outcome

Title	Percentage of Participants With Complete Early Virologic Response (cEVR)
Description	cEVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 12.
Time Frame	Treatment Week 12

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Measure Participants	12	39
Number (95% Confidence Interval) [Percentage of participants]	91.7 764.2%	92.3 236.7%

4. Secondary Outcome

Title	Percentage of Participants With End of the Treatment Response (EOTR)
Description	EOTR was defined as HCV RNA less than the lower limit of quantitation, target not detected at end of treatment.
Time Frame	End of the treatment (Week 12 for Cohort A, Week 24 for Cohort B)

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Measure Participants	12	39
Number (95% Confidence Interval) [Percentage of participants]	100 833.3%	100 256.4%

5. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24)
Description	SVR24 was defined as HCV RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24.
Time Frame	Follow-up Week 24

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Measure Participants	12	39
Number (95% Confidence Interval) [Percentage of participants]	66.7 555.8%	30.8 79%

6. Secondary Outcome

Title	Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment
Description	Cytopenic abnormalities were defined as anemia: Hemoglobin (Hb) <10 g/dL, and/or neutropenia: absolute neutrophils and bands (ANC) <750 mm^3, and/or thrombocytopenia: platelets <50,000 mm^3.
Time Frame	After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Measure Participants	12	39
Number (95% Confidence Interval) [Percentage of participants]	0 0%	0 0%

7. Secondary Outcome

Title	Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment
Description	Flu-like symptoms were defined as pyrexia or chills or pain. Musculoskeletal symptoms were defined as arthralgia or myalgia or back pain.
Time Frame	After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)

Outcome Measure Data

Analysis Population Description

mITT population.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Measure Participants	12	39
Flu-like symptoms	8.3 69.2%	12.8 32.8%
Musculoskeletal symptoms	0 0%	15.4 39.5%

8. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death
Description	AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug.
Time Frame	From Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B)

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Measure Participants	12	39
AEs on treatment	10 83.3%	38 97.4%
SAEs	0 0%	4 10.3%
Death	0 0%	0 0%
AE leading to discontinuation	1 8.3%	3 7.7%
Dose reduction - Lambda	0 0%	1 2.6%
Dose reduction - RBV	0 0%	2 5.1%

9. Secondary Outcome

Title	Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities
Description	Laboratory abnormalities were determined and graded using the Division of acquired immunodeficiency syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, version 1.0. International Normalized Ratio (INR): >2.0*Upper limit of normal (ULN); Alanine aminotransferase (ALT) : >5*ULN; Aspartate aminotransferase (AST): >5*ULN; Prothrombin Time (PT): >1.50*ULN; Bilirubin (Total): >2.5*ULN; Triglycerides (fasting): >750 mg/dL.
Time Frame	After day 1 to to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).	Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
Measure Participants	12	39
INR	0 0%	1 2.6%
ALT	2 16.7%	1 2.6%
AST	0 0%	2 5.1%
PT	0 0%	1 2.6%
Bilirubin	2 16.7%	7 17.9%
Triglycerides	0 0%	1 2.6%

Adverse Events

Time Frame	From Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B)
Arm/Group Title	Cohort A		Cohort B
Arm/Group Description	Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).		Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing <75 kg = 1000 mg and participants weighing >=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks).
All Cause Mortality
	Cohort A		Cohort B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/39 (0%)
Serious Adverse Events
	Cohort A		Cohort B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		4/39 (10.3%)
Gastrointestinal disorders
Haemorrhoids	0/12 (0%)	0	1/39 (2.6%)	1
Hepatobiliary disorders
Hepatitis acute	0/12 (0%)	0	1/39 (2.6%)	1
Jaundice	0/12 (0%)	0	1/39 (2.6%)	1
Infections and infestations
Arthritis bacterial	0/12 (0%)	0	1/39 (2.6%)	1
Other (Not Including Serious) Adverse Events
	Cohort A		Cohort B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/12 (83.3%)		36/39 (92.3%)
Blood and lymphatic system disorders
Anaemia	1/12 (8.3%)	1	0/39 (0%)	0
Endocrine disorders
Hypothyroidism	1/12 (8.3%)	1	0/39 (0%)	0
Gastrointestinal disorders
Nausea	2/12 (16.7%)	2	8/39 (20.5%)	8
Diarrhoea	0/12 (0%)	0	6/39 (15.4%)	6
Abdominal pain	0/12 (0%)	0	3/39 (7.7%)	3
Dry mouth	0/12 (0%)	0	3/39 (7.7%)	3
Dyspepsia	1/12 (8.3%)	1	2/39 (5.1%)	2
Rectal haemorrhage	0/12 (0%)	0	2/39 (5.1%)	2
Vomiting	0/12 (0%)	0	2/39 (5.1%)	2
General disorders
Asthenia	0/12 (0%)	0	12/39 (30.8%)	12
Fatigue	3/12 (25%)	3	9/39 (23.1%)	9
Pyrexia	1/12 (8.3%)	1	5/39 (12.8%)	5
Influenza like illness	1/12 (8.3%)	1	0/39 (0%)	0
Pain	1/12 (8.3%)	1	0/39 (0%)	0
Investigations
Blood bilirubin increased	2/12 (16.7%)	2	2/39 (5.1%)	2
Weight decreased	1/12 (8.3%)	1	2/39 (5.1%)	2
Alanine aminotransferase increased	1/12 (8.3%)	1	1/39 (2.6%)	1
Lipase increased	1/12 (8.3%)	1	1/39 (2.6%)	1
Blood bicarbonate decreased	1/12 (8.3%)	1	0/39 (0%)	0
Gamma-glutamyltransferase increased	1/12 (8.3%)	1	0/39 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	2/12 (16.7%)	2	5/39 (12.8%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)	0	4/39 (10.3%)	4
Haemarthrosis	0/12 (0%)	0	2/39 (5.1%)	2
Myalgia	0/12 (0%)	0	2/39 (5.1%)	2
Nervous system disorders
Headache	1/12 (8.3%)	1	7/39 (17.9%)	7
Dizziness	0/12 (0%)	0	3/39 (7.7%)	3
Disturbance in attention	0/12 (0%)	0	2/39 (5.1%)	2
Psychiatric disorders
Insomnia	3/12 (25%)	3	13/39 (33.3%)	13
Sleep disorder	1/12 (8.3%)	1	5/39 (12.8%)	5
Affect lability	0/12 (0%)	0	2/39 (5.1%)	2
Anger	0/12 (0%)	0	2/39 (5.1%)	2
Anxiety	0/12 (0%)	0	2/39 (5.1%)	2
Irritability	2/12 (16.7%)	2	2/39 (5.1%)	2
Depression	1/12 (8.3%)	1	0/39 (0%)	0
Initial insomnia	1/12 (8.3%)	1	0/39 (0%)	0
Renal and urinary disorders
Chromaturia	2/12 (16.7%)	2	4/39 (10.3%)	4
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)	0	3/39 (7.7%)	3
Dyspnoea	1/12 (8.3%)	1	0/39 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	1/12 (8.3%)	1	7/39 (17.9%)	7
Dry skin	0/12 (0%)	0	4/39 (10.3%)	4
Rash	1/12 (8.3%)	1	1/39 (2.6%)	1
Vascular disorders
Haematoma	0/12 (0%)	0	3/39 (7.7%)	3
Haemorrhage	0/12 (0%)	0	2/39 (5.1%)	2

Limitations/Caveats

[Not Specified]

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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 submitting 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.