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Efficacy and Safety of Alisporivir Triple Therapy in Chronic Hepatitis C Genotype 1 Treatment-naïve Participants

Sponsor
Debiopharm International SA (Industry)
Overall Status
Completed
CT.gov ID
NCT01318694
Collaborator
(none)
1,081
Enrollment
147
Locations
4
Arms
29
Duration (Months)
7.4
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will assess the safety and efficacy of alisporivir (ALV; DEB025) triple therapy [i.e., when added to peginterferon alfa-2a (PEG) and ribavirin (RBV)] to optimize treatment in treatment-naïve participants with hepatitis C virus (HCV) genotype 1 (GT1)

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1081 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of DEB025/Alisporivir in Combination With Peg-IFNα2a and Ribavirin in Hepatitis C Genotype 1 Treatment-naïve Patients
Study Start Date :
Mar 1, 2011
Actual Primary Completion Date :
Aug 1, 2013
Actual Study Completion Date :
Aug 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment Arm A

Alisporivir (ALV) 600 mg twice daily (BID) with Peginterferon alfa-2a (PEG) and ribavirin (RBV) for 1 week, followed by an additional 23 or 47 weeks according to response-guided treatment duration (RGT): Participants with a viral load below the level of detection (< LOD) at Week 4 stop study treatment after 24 weeks Participants with a viral load ≥ LOD at Week 4 complete 48 weeks of study treatment

Drug: Alisporivir
ALV 200 mg soft gel capsules administered orally
Other Names:
  • DEB025
  • ALV

    • Drug: Peginterferon alfa-2a
    PEG 180 μg administered via subcutaneous (s.c.) injection once weekly
    Other Names:
  • Pegasys®
  • PEG

    • Drug: Ribavirin
    RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose
    Other Names:
  • Copegus®
  • RBV

    		•
    Experimental: Treatment Arm B

    Alisporivir (ALV) 400 mg twice daily (BID) with PEG and RBV for 24 or 48 weeks according to response-guided treatment duration (RGT)

    Drug: Alisporivir
    ALV 200 mg soft gel capsules administered orally
    Other Names:
  • DEB025
  • ALV

    • Drug: Peginterferon alfa-2a
    PEG 180 μg administered via subcutaneous (s.c.) injection once weekly
    Other Names:
  • Pegasys®
  • PEG

    • Drug: Ribavirin
    RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose
    Other Names:
  • Copegus®
  • RBV

    		•
    Experimental: Treatment Arm C

    Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg once daily (QD) for 47 weeks

    Drug: Alisporivir
    ALV 200 mg soft gel capsules administered orally
    Other Names:
  • DEB025
  • ALV

    • Drug: Peginterferon alfa-2a
    PEG 180 μg administered via subcutaneous (s.c.) injection once weekly
    Other Names:
  • Pegasys®
  • PEG

    • Drug: Ribavirin
    RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose
    Other Names:
  • Copegus®
  • RBV

    		•
    Active Comparator: Treatment Arm D

    ALV Placebo with PEG and RBV for 48 weeks

    Drug: Peginterferon alfa-2a
    PEG 180 μg administered via subcutaneous (s.c.) injection once weekly
    Other Names:
  • Pegasys®
  • PEG

    • Drug: Ribavirin
    RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose
    Other Names:
  • Copegus®
  • RBV

    • Drug: ALV Placebo
    ALV placebo soft gel capsules administered orally
    Other Names:
  • Placebo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Who Achieved Sustained Virologic Response (SVR) 12 Weeks After the End of Treatment (SVR12) [12 weeks after the end of treatment]

      SVR12 was defined as hepatitis C virus (HCV) RNA laboratory value below the level of quantification (< LOQ; i.e., 25 IU/ml) 12 weeks after the end of treatment.

    Secondary Outcome Measures

    1. Percentage of Participants Who Achieved SVR 24 Weeks After the End of Treatment (SVR24) [24 weeks after the end of treatment]

      SVR24 was defined as HCV RNA laboratory value < LOQ 24 weeks after the end of treatment.

    2. Percentage of Participants With Rapid Virologic Response (RVR) After 4 Weeks of Treatment (RVR4) [after 4 weeks of treatment]

      RVR4 was defined as serum HCV RNA < LOQ after 4 weeks of treatment.

    3. Percentage of Participants With Early Virologic Response (EVR) After 12 Weeks of Treatment [after 12 weeks of treatment]

      EVR was defined as a ≥ 2 log10 decrease in HCV RNA or HCV RNA < LOQ after 12 weeks of treatment.

    4. Percentage of Participants With Partial Early Virologic Response (pEVR) After 12 Weeks of Treatment [after 12 weeks of treatment]

      pEVR was defined as a ≥ 2 log10 decrease in HCV RNA and still detectable (≥ LOQ) after 12 weeks of treatment.

    5. Percentage of Participants With Complete Early Virologic Response (cEVR) After 12 Weeks of Treatment [after 12 weeks of treatment]

      cEVR was defined as serum HCV RNA < LOQ after 12 weeks of treatment.

    6. Percentage of Participants With Extended Rapid Virologic Response (eRVR) From 4 to 12 Weeks of Treatment [from 4 to 12 weeks of treatment]

      eRVR was defined as achieving RVR4 and maintaining HCV RNA < LOQ until Week 12.

    7. Percentage of Participants With End of Treatment Response (ETR) at Treatment End Within 48 Weeks [at treatment end within 48 weeks]

      ETR was defined as serum HCV RNA < LOQ at treatment end (completed or prematurely discontinued).

    8. Percentage of Participants With Alanine Aminotransferase (ALT) Abnormalities Within 48 Weeks [within 48 weeks]

      ALT abnormalities were summarized as participants who had either: ALT > 2 x upper limit of normal (ULN) during the study and > 2 x ULN at baseline ALT > 3 x ULN during the study and > 2 x ULN at baseline

    9. Percentage of Participants With Grade 3 or 4 Anemia During Treatment Within 48 Weeks [within 48 weeks]

      Grading was according to the Modified Division of Microbiology & Infectious Diseases (DMID) Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.

    10. Percentage of Participants With Grade 3 or 4 Neutropenia During Treatment Within 48 Weeks [within 48 weeks]

      Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.

    11. Percentage of Participants With Grade 3 or 4 Thrombocytopenia During Treatment Within 48 Weeks [within 48 weeks]

      Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion criteria:

    • Chronic HCV infection

    • HCV genotype 1

    • No previous treatment for hepatitis C infection

    • Serum HCV RNA level ≥ 1000 IU/ml assessed by quantitative polymerase chain reaction or equivalent at screening, no upper limit

    • Liver evaluation prior to baseline: liver biopsy within 3 years or Fibroscan within 6 months

    Exclusion criteria:

    • HCV genotype different from genotype 1 or co-infection with other HCV genotype

    • Co-infection with Hepatitis B or HIV

    • Any other cause of relevant liver disease other than HCV

    • Presence or history of hepatic decompensation

    • Alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN), more than 1 episode of elevated bilirubin (> ULN) in past 6 months

    Other protocol-defined inclusion/exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Beverly Hills California United States 90211
    2 Novartis Investigative Site Oakland California United States 94612
    3 Novartis Investigative Site San Diego California United States 92101
    4 Novartis Investigative Site San Diego California United States 92123
    5 Novartis Investigative Site San Diego California United States 92128
    6 Novartis Investigative Site Ventura California United States 93003
    7 Novartis Investigative Site Bradenton Florida United States 34209
    8 Novartis Investigative Site Maitland Florida United States 32751
    9 Novartis Investigative Site Tampa Florida United States 33607
    10 Novartis Investigative Site Springfield Illinois United States 62703
    11 Novartis Investigative Site Indianapolis Indiana United States 46237
    12 Novartis Investigative Site Shreveport Louisiana United States 71130-3932
    13 Novartis Investigative Site Baltimore Maryland United States 21202
    14 Novartis Investigative Site Baltimore Maryland United States 21229
    15 Novartis Investigative Site Minneapolis Minnesota United States 55404
    16 Novartis Investigative Site St. Louis Missouri United States 63110
    17 Novartis Investigative Site St. Louis Missouri United States 63128
    18 Novartis Investigative Site Omaha Nebraska United States 68198
    19 Novartis Investigative Site Newark New Jersey United States 07102
    20 Novartis Investigative Site Brooklyn New York United States 11230
    21 Novartis Investigative Site New York New York United States 10016
    22 Novartis Investigative Site New York New York United States 10021
    23 Novartis Investigative Site Charlotte North Carolina United States 28203
    24 Novartis Investigative Site Fayetteville North Carolina United States 28304
    25 Novartis Investigative Site Arlington Texas United States 76012
    26 Novartis Investigative Site Dallas Texas United States 75246-2096
    27 Novartis Investigative Site Dallas Texas United States 75390
    28 Novartis Investigative Site Houston Texas United States 77030
    29 Novartis Investigative Site San Antonio Texas United States 78215
    30 Novartis Investigative Site Salt Lake City Utah United States 84124
    31 Novartis Investigative Site Fairfax Virginia United States 22031
    32 Novartis Investigative Site Newport News Virginia United States 23602
    33 Novartis Investigative Site Rosario Santa Fe Argentina S2000DSV
    34 Novartis Investigative Site Rosario Santa Fe Argentina S2002KDS
    35 Novartis Investigative Site Buenos Aires Argentina C1125ABE
    36 Novartis Investigative Site Buenos Aires Argentina C1405BCK
    37 Novartis Investigative Site Cordoba Argentina X5004BAL
    38 Novartis Investigative Site Darlinghurst New South Wales Australia 2010
    39 Novartis Investigative Site Kingswood New South Wales Australia 2747
    40 Novartis Investigative Site Kogarah New South Wales Australia 2217
    41 Novartis Investigative Site Westmead New South Wales Australia 2145
    42 Novartis Investigative Site Greenslopes Queensland Australia 4120
    43 Novartis Investigative Site Fitzroy Victoria Australia 3065
    44 Novartis Investigative Site Brussel Belgium 1090
    45 Novartis Investigative Site Bruxelles Belgium 1070
    46 Novartis Investigative Site Gent Belgium 9000
    47 Novartis Investigative Site Calgary Alberta Canada T2N 4n1
    48 Novartis Investigative Site Vancouver British Columbia Canada V5Z 1J4
    49 Novartis Investigative Site Vancouver British Columbia Canada V5Z 1M9
    50 Novartis Investigative Site Vancouver British Columbia Canada v6z 2k5
    51 Novartis Investigative Site Downsview Ontario Canada M3N 2Z9
    52 Novartis Investigative Site London Ontario Canada N6A 4G5
    53 Novartis Investigative Site Toronto Ontario Canada M5G 2C4
    54 Novartis Investigative Site Toronto Ontario Canada M5T 2S8
    55 Novartis Investigative Site Clichy France 92110
    56 Novartis Investigative Site Grenoble France 38043
    57 Novartis Investigative Site Lyon Cedex 04 France 69317
    58 Novartis Investigative Site Toulouse cedex 9 France 31059
    59 Novartis Investigative Site Villejuif France 94805
    60 Novartis Investigative Site Berlin Germany 10969
    61 Novartis Investigative Site Berlin Germany 13353
    62 Novartis Investigative Site Essen Germany 45147
    63 Novartis Investigative Site Frankfurt Germany 60590
    64 Novartis Investigative Site Freiburg Germany 79106
    65 Novartis Investigative Site Hamburg Germany 20099
    66 Novartis Investigative Site Hannover Germany 30625
    67 Novartis Investigative Site Kiel Germany 24146
    68 Novartis Investigative Site Köln Germany 50937
    69 Novartis Investigative Site Leipzig Germany 04103
    70 Novartis Investigative Site Mainz Germany 55131
    71 Novartis Investigative Site Hong Kong Hong Kong
    72 Novartis Investigative Site Hongkong Hong Kong
    73 Novartis Investigative Site Bekescsaba Hungary H-5600
    74 Novartis Investigative Site Budapest Hungary 1083
    75 Novartis Investigative Site Budapest Hungary 1097
    76 Novartis Investigative Site Budapest Hungary 1126
    77 Novartis Investigative Site Debrecen Hungary 4032
    78 Novartis Investigative Site Kaposvár Hungary 7400
    79 Novartis Investigative Site Pecs Hungary 7624
    80 Novartis Investigative Site Szekesfehervar Hungary 8000
    81 Novartis Investigative Site Bologna BO Italy 40138
    82 Novartis Investigative Site Genova GE Italy 16132
    83 Novartis Investigative Site Milano MI Italy 20121
    84 Novartis Investigative Site Milano MI Italy 20122
    85 Novartis Investigative Site Milano MI Italy 20162
    86 Novartis Investigative Site Rozzano MI Italy 20089
    87 Novartis Investigative Site Palermo PA Italy 90127
    88 Novartis Investigative Site Padova PD Italy 35128
    89 Novartis Investigative Site Pavia PV Italy 27100
    90 Novartis Investigative Site Roma RM Italy 00133
    91 Novartis Investigative Site Torino TO Italy 10126
    92 Novartis Investigative Site Bologna Italy 40138
    93 Novartis Investigative Site Napoli Italy 80135
    94 Novartis Investigative Site Yangsan-si Gyeongsangnam-Do Korea, Republic of 626-770
    95 Novartis Investigative Site Seoul Korea Korea, Republic of 03722
    96 Novartis Investigative Site Seoul Korea Korea, Republic of 05505
    97 Novartis Investigative Site Kyunggi Kyeonggi Korea, Republic of 463-712
    98 Novartis Investigative Site Busan Korea, Republic of 602-715
    99 Novartis Investigative Site Busan Korea, Republic of 602-739
    100 Novartis Investigative Site Incheon Korea, Republic of 22332
    101 Novartis Investigative Site Pusan Korea, Republic of 614-735
    102 Novartis Investigative Site México Distrito Federal Mexico 14000
    103 Novartis Investigative Site Monterrey Nuevo León Mexico 64020
    104 Novartis Investigative Site Bialystok Poland 15-540
    105 Novartis Investigative Site Bydgoszcz Poland 85-030
    106 Novartis Investigative Site Chorzów Poland 41-500
    107 Novartis Investigative Site Kielce Poland 25-317
    108 Novartis Investigative Site Lódz Poland 91-347
    109 Novartis Investigative Site San Juan Puerto Rico 00909
    110 Novartis Investigative Site Bucharest District 1 Romania 050524
    111 Novartis Investigative Site Bucharest District 3 Romania 030317
    112 Novartis Investigative Site Iasi Jud. Iasi Romania 700111
    113 Novartis Investigative Site Bucharest Romania 020125
    114 Novartis Investigative Site Cluj Napoca Romania 400006
    115 Novartis Investigative Site Craiova Romania 200515
    116 Novartis Investigative Site Iasi Romania 700506
    117 Novartis Investigative Site Moscow Russian Federation 111123
    118 Novartis Investigative Site Moscow Russian Federation 119333
    119 Novartis Investigative Site Moscow Russian Federation 119992
    120 Novartis Investigative Site Moscow Russian Federation 127473
    121 Novartis Investigative Site Saint-Petersburg Russian Federation 194044
    122 Novartis Investigative Site St.- Petersburg Russian Federation 197376
    123 Novartis Investigative Site Sevilla Andalucia Spain 41014
    124 Novartis Investigative Site Barcelona Catalunya Spain 08003
    125 Novartis Investigative Site Barcelona Catalunya Spain 08035
    126 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46014
    127 Novartis Investigative Site Majadahonda Madrid Spain 28222
    128 Novartis Investigative Site Madrid Spain 28029
    129 Novartis Investigative Site Chia-Yi Taiwan 600
    130 Novartis Investigative Site Kaohsiung Taiwan 807
    131 Novartis Investigative Site Niaosong Township Taiwan 83301
    132 Novartis Investigative Site Taichung Taiwan 40447
    133 Novartis Investigative Site Taipei Taiwan 10002
    134 Novartis Investigative Site Yun-Lin Taiwan 640
    135 Novartis Investigative Site Bangkok Thailand 10330
    136 Novartis Investigative Site Bangkok Thailand 10700
    137 Novartis Investigative Site Chiang Mai Thailand 50200
    138 Novartis Investigative Site Khon Kaen Thailand 40002
    139 Novartis Investigative Site Songkla Thailand 90110
    140 Novartis Investigative Site Birmingham United Kingdom B15 2TT
    141 Novartis Investigative Site London United Kingdom E1 1BB
    142 Novartis Investigative Site London United Kingdom SE5 9RS
    143 Novartis Investigative Site London United Kingdom W2 1NY
    144 Novartis Investigative Site Newcastle Upon Tyne United Kingdom NE7 7DN
    145 Novartis Investigative Site Nottingham United Kingdom NG7 2UH
    146 Novartis Investigative Site Hanoi Vietnam
    147 Novartis Investigative Site Ho Chi Minh Vietnam

    Sponsors and Collaborators

    • Debiopharm International SA

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Debiopharm International SA
    ClinicalTrials.gov Identifier:
    NCT01318694
    Other Study ID Numbers:
    • CDEB025A2301
    • 2010-022867-37
    First Posted:
    Mar 18, 2011
    Last Update Posted:
    Sep 30, 2016
    Last Verified:
    Aug 1, 2016
    Keywords provided by Debiopharm International SA
    Chronic hepatitis C
    Cyclophilin inhibitor
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis C
    Hepatitis
    Ribavirin
    Peginterferon alfa-2a

    Study Results

    Participant Flow

    Recruitment Details Of the 1580 patients screened at multiple global sites, 1081 (68.4%) were randomized and 499 (31.6%) discontinued from the study prior to randomization.
    Pre-assignment Detail Due to mis-randomization, four patients did not have a baseline visit and never started study medications. They were included in screened and randomized, but excluded from the Full Analysis Set and the Safety Set.
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg twice daily (BID) with Peginterferon alfa-2a (PEG) and ribavirin (RBV) for 1 week, followed by an additional 23 or 47 weeks according to response-guided treatment duration (RGT) Alisporivir (ALV) 400 mg twice daily (BID) with PEG and RBV for 24 or 48 weeks according to response-guided treatment duration (RGT) Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg once daily (QD) for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Period Title: Overall Study
    STARTED 275 270 268 268
    Full Analysis Set 274 270 265 268
    Safety Set 273 268 265 265
    COMPLETED 223 212 225 200
    NOT COMPLETED 52 58 43 68

    Baseline Characteristics

    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D Total
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks Total of all reporting groups
    Overall Participants 274 270 265 268 1077
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    45.9
    (11.08)
    45.8
    (11.95)
    45.5
    (12.15)
    46.3
    (11.53)
    45.9
    (11.67)
    Sex: Female, Male (Count of Participants)
    Female
    113
    41.2%
    106
    39.3%
    134
    50.6%
    114
    42.5%
    467
    43.4%
    Male
    161
    58.8%
    164
    60.7%
    131
    49.4%
    154
    57.5%
    610
    56.6%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Who Achieved Sustained Virologic Response (SVR) 12 Weeks After the End of Treatment (SVR12)
    Description SVR12 was defined as hepatitis C virus (HCV) RNA laboratory value below the level of quantification (< LOQ; i.e., 25 IU/ml) 12 weeks after the end of treatment.
    Time Frame 12 weeks after the end of treatment

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 274 270 265 268
    Number [percentage of participants]
    68.6
    25%
    68.9
    25.5%
    69.4
    26.2%
    52.5
    19.6%
    2. Secondary Outcome
    Title Percentage of Participants Who Achieved SVR 24 Weeks After the End of Treatment (SVR24)
    Description SVR24 was defined as HCV RNA laboratory value < LOQ 24 weeks after the end of treatment.
    Time Frame 24 weeks after the end of treatment

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 273 268 265 265
    Number [percentage of participants]
    68.5
    25%
    69.0
    25.6%
    68.3
    25.8%
    51.7
    19.3%
    3. Secondary Outcome
    Title Percentage of Participants With Rapid Virologic Response (RVR) After 4 Weeks of Treatment (RVR4)
    Description RVR4 was defined as serum HCV RNA < LOQ after 4 weeks of treatment.
    Time Frame after 4 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 268 258 258 261
    Number [percentage of participants]
    60.1
    21.9%
    72.5
    26.9%
    56.6
    21.4%
    28.4
    10.6%
    4. Secondary Outcome
    Title Percentage of Participants With Early Virologic Response (EVR) After 12 Weeks of Treatment
    Description EVR was defined as a ≥ 2 log10 decrease in HCV RNA or HCV RNA < LOQ after 12 weeks of treatment.
    Time Frame after 12 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 259 242 247 256
    Number [percentage of participants]
    97.7
    35.7%
    98.3
    36.4%
    99.6
    37.6%
    89.8
    33.5%
    5. Secondary Outcome
    Title Percentage of Participants With Partial Early Virologic Response (pEVR) After 12 Weeks of Treatment
    Description pEVR was defined as a ≥ 2 log10 decrease in HCV RNA and still detectable (≥ LOQ) after 12 weeks of treatment.
    Time Frame after 12 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 259 242 247 256
    Number [percentage of participants]
    8.1
    3%
    2.1
    0.8%
    10.5
    4%
    19.5
    7.3%
    6. Secondary Outcome
    Title Percentage of Participants With Complete Early Virologic Response (cEVR) After 12 Weeks of Treatment
    Description cEVR was defined as serum HCV RNA < LOQ after 12 weeks of treatment.
    Time Frame after 12 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 259 242 247 256
    Number [percentage of participants]
    89.6
    32.7%
    96.3
    35.7%
    89.1
    33.6%
    70.3
    26.2%
    7. Secondary Outcome
    Title Percentage of Participants With Extended Rapid Virologic Response (eRVR) From 4 to 12 Weeks of Treatment
    Description eRVR was defined as achieving RVR4 and maintaining HCV RNA < LOQ until Week 12.
    Time Frame from 4 to 12 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 259 242 247 256
    Number [percentage of participants]
    60.2
    22%
    71.1
    26.3%
    56.7
    21.4%
    28.1
    10.5%
    8. Secondary Outcome
    Title Percentage of Participants With End of Treatment Response (ETR) at Treatment End Within 48 Weeks
    Description ETR was defined as serum HCV RNA < LOQ at treatment end (completed or prematurely discontinued).
    Time Frame at treatment end within 48 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 271 268 264 265
    Number [percentage of participants]
    88.2
    32.2%
    87.7
    32.5%
    87.5
    33%
    80.0
    29.9%
    9. Secondary Outcome
    Title Percentage of Participants With Alanine Aminotransferase (ALT) Abnormalities Within 48 Weeks
    Description ALT abnormalities were summarized as participants who had either: ALT > 2 x upper limit of normal (ULN) during the study and > 2 x ULN at baseline ALT > 3 x ULN during the study and > 2 x ULN at baseline
    Time Frame within 48 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Set, defined as having received at least one dose of study medication, with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 271 267 264 264
    > 2 x ULN and > 2 x baseline
    1.5
    0.5%
    0.4
    0.1%
    1.9
    0.7%
    1.5
    0.6%
    > 3 x ULN and > 2 x baseline
    0.7
    0.3%
    0.0
    0%
    1.5
    0.6%
    0.8
    0.3%
    10. Secondary Outcome
    Title Percentage of Participants With Grade 3 or 4 Anemia During Treatment Within 48 Weeks
    Description Grading was according to the Modified Division of Microbiology & Infectious Diseases (DMID) Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.
    Time Frame within 48 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 271 267 264 264
    Grade 3
    1.8
    0.7%
    3.4
    1.3%
    0.8
    0.3%
    1.9
    0.7%
    Grade 4
    0.0
    0%
    0.4
    0.1%
    0.0
    0%
    0.0
    0%
    11. Secondary Outcome
    Title Percentage of Participants With Grade 3 or 4 Neutropenia During Treatment Within 48 Weeks
    Description Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.
    Time Frame within 48 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 270 263 264 264
    Grade 3
    24.4
    8.9%
    24.7
    9.1%
    23.1
    8.7%
    12.9
    4.8%
    Grade 4
    4.4
    1.6%
    8.0
    3%
    7.2
    2.7%
    2.7
    1%
    12. Secondary Outcome
    Title Percentage of Participants With Grade 3 or 4 Thrombocytopenia During Treatment Within 48 Weeks
    Description Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.
    Time Frame within 48 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Set with available data
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    Measure Participants 270 265 264 264
    Grade 3
    6.7
    2.4%
    21.9
    8.1%
    12.5
    4.7%
    1.9
    0.7%
    Grade 4
    0.0
    0%
    1.1
    0.4%
    0.0
    0%
    0.0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Arm/Group Description Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT Alisporivir (ALV) 400 mg twice daily (BID) with PEG and RBV for 24 or 48 weeks according to response-guided treatment duration (RGT) Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks ALV Placebo with PEG and RBV for 48 weeks
    All Cause Mortality
    Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/273 (8.8%) 28/268 (10.4%) 21/265 (7.9%) 28/265 (10.6%)
    Blood and lymphatic system disorders
    Anaemia 2/273 (0.7%) 1/268 (0.4%) 0/265 (0%) 2/265 (0.8%)
    Neutropenia 2/273 (0.7%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Febrile neutropenia 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Pancytopenia 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Spontaneous haematoma 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Thrombocytopenia 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Cardiac disorders
    Tachycardia 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 1/265 (0.4%)
    Atrial fibrillation 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Cardiac failure 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Hypertensive heart disease 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Ear and labyrinth disorders
    Vertigo 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 1/265 (0.4%)
    Acute vestibular syndrome 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Deafness neurosensory 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Endocrine disorders
    Thyroiditis 0/273 (0%) 0/268 (0%) 2/265 (0.8%) 0/265 (0%)
    Autoimmune thyroiditis 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Hyperthyroidism 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Eye disorders
    Dacryoadenitis acquired 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Gastrointestinal disorders
    Pancreatitis acute 0/273 (0%) 3/268 (1.1%) 1/265 (0.4%) 1/265 (0.4%)
    Vomiting 0/273 (0%) 2/268 (0.7%) 0/265 (0%) 2/265 (0.8%)
    Abdominal pain 0/273 (0%) 2/268 (0.7%) 0/265 (0%) 1/265 (0.4%)
    Nausea 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Pancreatitis 1/273 (0.4%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Diarrhoea 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Gastritis 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Haematemesis 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Haemorrhoidal haemorrhage 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Haemorrhoids 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Small intestinal obstruction 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Upper gastrointestinal haemorrhage 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    General disorders
    Pyrexia 1/273 (0.4%) 2/268 (0.7%) 0/265 (0%) 0/265 (0%)
    Drug interaction 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Fatigue 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Influenza like illness 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Lipogranuloma 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Multi-organ failure 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Non-cardiac chest pain 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Pain 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Cholecystitis acute 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Cholelithiasis 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Hepatosplenomegaly 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Infections and infestations
    Appendicitis 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 2/265 (0.8%)
    Bronchitis 1/273 (0.4%) 2/268 (0.7%) 0/265 (0%) 0/265 (0%)
    Pneumonia 1/273 (0.4%) 1/268 (0.4%) 1/265 (0.4%) 0/265 (0%)
    Urinary tract infection 2/273 (0.7%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Bronchopneumonia 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Cellulitis 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Cervicitis 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Enterocolitis infectious 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Gastroenteritis 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Influenza 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Lobar pneumonia 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Nasal abscess 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Pulmonary tuberculosis 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Salpingo-oophoritis 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Tooth abscess 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Injury, poisoning and procedural complications
    Lower limb fracture 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Radius fracture 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Road traffic accident 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Metabolism and nutrition disorders
    Diabetic ketoacidosis 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Hypokalaemia 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Hypomagnesaemia 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Hyponatraemia 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Type 2 diabetes mellitus 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Musculoskeletal and connective tissue disorders
    Bursitis 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Exostosis 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Cervix carcinoma 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Craniopharyngioma 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Hepatocellular carcinoma 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Leiomyosarcoma 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Meningioma 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Pancreatic neoplasm 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Pituitary tumour benign 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Prostatic adenoma 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Squamous cell carcinoma of the cervix 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Nervous system disorders
    Dizziness 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 1/265 (0.4%)
    Headache 0/273 (0%) 1/268 (0.4%) 1/265 (0.4%) 0/265 (0%)
    Subarachnoid haemorrhage 1/273 (0.4%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Syncope 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 1/265 (0.4%)
    Hemiparesis 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Intraventricular haemorrhage 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Paraesthesia 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Psychiatric disorders
    Depression 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Mania 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 1/265 (0.4%)
    Suicidal ideation 0/273 (0%) 2/268 (0.7%) 0/265 (0%) 0/265 (0%)
    Anxiety 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Major depression 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Schizophrenia, paranoid type 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Suicide attempt 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Reproductive system and breast disorders
    Bartholinitis 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Benign prostatic hyperplasia 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Dysfunctional uterine bleeding 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Ovarian disorder 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary fibrosis 0/273 (0%) 0/268 (0%) 2/265 (0.8%) 0/265 (0%)
    Acute respiratory failure 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Chronic obstructive pulmonary disease 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Dyspnoea 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Epistaxis 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Tonsillar hypertrophy 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Skin and subcutaneous tissue disorders
    Eczema 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Urticaria 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Vascular disorders
    Hypertensive crisis 0/273 (0%) 3/268 (1.1%) 0/265 (0%) 0/265 (0%)
    Hypertension 0/273 (0%) 1/268 (0.4%) 1/265 (0.4%) 0/265 (0%)
    Aortic dissection 0/273 (0%) 0/268 (0%) 0/265 (0%) 1/265 (0.4%)
    Deep vein thrombosis 0/273 (0%) 1/268 (0.4%) 0/265 (0%) 0/265 (0%)
    Hypotension 1/273 (0.4%) 0/268 (0%) 0/265 (0%) 0/265 (0%)
    Vasculitis 0/273 (0%) 0/268 (0%) 1/265 (0.4%) 0/265 (0%)
    Other (Not Including Serious) Adverse Events
    Treatment Arm A Treatment Arm B Treatment Arm C Treatment Arm D
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 256/273 (93.8%) 261/268 (97.4%) 250/265 (94.3%) 242/265 (91.3%)
    Blood and lymphatic system disorders
    Anaemia 113/273 (41.4%) 124/268 (46.3%) 91/265 (34.3%) 88/265 (33.2%)
    Leukopenia 48/273 (17.6%) 27/268 (10.1%) 48/265 (18.1%) 27/265 (10.2%)
    Lymphopenia 15/273 (5.5%) 7/268 (2.6%) 16/265 (6%) 8/265 (3%)
    Neutropenia 86/273 (31.5%) 80/268 (29.9%) 86/265 (32.5%) 67/265 (25.3%)
    Thrombocytopenia 47/273 (17.2%) 73/268 (27.2%) 49/265 (18.5%) 16/265 (6%)
    Endocrine disorders
    Hypothyroidism 17/273 (6.2%) 22/268 (8.2%) 23/265 (8.7%) 12/265 (4.5%)
    Eye disorders
    Ocular icterus 11/273 (4%) 14/268 (5.2%) 5/265 (1.9%) 4/265 (1.5%)
    Gastrointestinal disorders
    Abdominal pain upper 18/273 (6.6%) 24/268 (9%) 22/265 (8.3%) 15/265 (5.7%)
    Constipation 12/273 (4.4%) 17/268 (6.3%) 7/265 (2.6%) 12/265 (4.5%)
    Diarrhoea 30/273 (11%) 27/268 (10.1%) 38/265 (14.3%) 37/265 (14%)
    Dyspepsia 23/273 (8.4%) 17/268 (6.3%) 32/265 (12.1%) 18/265 (6.8%)
    Gastrooesophageal reflux disease 11/273 (4%) 9/268 (3.4%) 7/265 (2.6%) 15/265 (5.7%)
    Nausea 66/273 (24.2%) 67/268 (25%) 62/265 (23.4%) 45/265 (17%)
    Vomiting 26/273 (9.5%) 39/268 (14.6%) 29/265 (10.9%) 19/265 (7.2%)
    General disorders
    Asthenia 43/273 (15.8%) 46/268 (17.2%) 46/265 (17.4%) 48/265 (18.1%)
    Chills 23/273 (8.4%) 30/268 (11.2%) 33/265 (12.5%) 21/265 (7.9%)
    Fatigue 84/273 (30.8%) 99/268 (36.9%) 87/265 (32.8%) 86/265 (32.5%)
    Influenza like illness 56/273 (20.5%) 52/268 (19.4%) 38/265 (14.3%) 40/265 (15.1%)
    Injection site erythema 14/273 (5.1%) 10/268 (3.7%) 17/265 (6.4%) 8/265 (3%)
    Irritability 19/273 (7%) 16/268 (6%) 21/265 (7.9%) 22/265 (8.3%)
    Pyrexia 78/273 (28.6%) 93/268 (34.7%) 82/265 (30.9%) 74/265 (27.9%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 32/273 (11.7%) 61/268 (22.8%) 25/265 (9.4%) 2/265 (0.8%)
    Jaundice 7/273 (2.6%) 20/268 (7.5%) 3/265 (1.1%) 1/265 (0.4%)
    Infections and infestations
    Nasopharyngitis 9/273 (3.3%) 9/268 (3.4%) 17/265 (6.4%) 12/265 (4.5%)
    Upper respiratory tract infection 16/273 (5.9%) 5/268 (1.9%) 16/265 (6%) 13/265 (4.9%)
    Urinary tract infection 11/273 (4%) 14/268 (5.2%) 11/265 (4.2%) 8/265 (3%)
    Investigations
    Weight decreased 24/273 (8.8%) 28/268 (10.4%) 26/265 (9.8%) 18/265 (6.8%)
    Metabolism and nutrition disorders
    Decreased appetite 61/273 (22.3%) 59/268 (22%) 58/265 (21.9%) 42/265 (15.8%)
    Hypertriglyceridaemia 11/273 (4%) 23/268 (8.6%) 22/265 (8.3%) 14/265 (5.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 38/273 (13.9%) 35/268 (13.1%) 39/265 (14.7%) 29/265 (10.9%)
    Back pain 18/273 (6.6%) 14/268 (5.2%) 15/265 (5.7%) 20/265 (7.5%)
    Muscle spasms 8/273 (2.9%) 17/268 (6.3%) 7/265 (2.6%) 10/265 (3.8%)
    Myalgia 59/273 (21.6%) 53/268 (19.8%) 56/265 (21.1%) 52/265 (19.6%)
    Nervous system disorders
    Dizziness 33/273 (12.1%) 34/268 (12.7%) 25/265 (9.4%) 30/265 (11.3%)
    Dysgeusia 14/273 (5.1%) 22/268 (8.2%) 13/265 (4.9%) 11/265 (4.2%)
    Headache 91/273 (33.3%) 94/268 (35.1%) 94/265 (35.5%) 80/265 (30.2%)
    Psychiatric disorders
    Anxiety 17/273 (6.2%) 20/268 (7.5%) 25/265 (9.4%) 29/265 (10.9%)
    Depression 20/273 (7.3%) 29/268 (10.8%) 28/265 (10.6%) 23/265 (8.7%)
    Insomnia 49/273 (17.9%) 61/268 (22.8%) 50/265 (18.9%) 60/265 (22.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 47/273 (17.2%) 54/268 (20.1%) 59/265 (22.3%) 53/265 (20%)
    Dyspnoea 37/273 (13.6%) 26/268 (9.7%) 23/265 (8.7%) 26/265 (9.8%)
    Epistaxis 12/273 (4.4%) 25/268 (9.3%) 15/265 (5.7%) 10/265 (3.8%)
    Oropharyngeal pain 15/273 (5.5%) 13/268 (4.9%) 19/265 (7.2%) 11/265 (4.2%)
    Skin and subcutaneous tissue disorders
    Alopecia 60/273 (22%) 45/268 (16.8%) 57/265 (21.5%) 47/265 (17.7%)
    Dry skin 21/273 (7.7%) 23/268 (8.6%) 31/265 (11.7%) 22/265 (8.3%)
    Pruritus 58/273 (21.2%) 55/268 (20.5%) 49/265 (18.5%) 54/265 (20.4%)
    Rash 46/273 (16.8%) 40/268 (14.9%) 45/265 (17%) 45/265 (17%)
    Vascular disorders
    Hypertension 31/273 (11.4%) 50/268 (18.7%) 34/265 (12.8%) 7/265 (2.6%)

    Limitations/Caveats

    In April 2012, ALV and placebo were discontinued in all participants. Participants remained on PEG and RBV treatment.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Vice President Clinical Research & Development
    Organization Debiopharm International S.A.
    Phone 4121 321 01 11
    Email info-international@debiopharm.com
    Responsible Party:
    Debiopharm International SA
    ClinicalTrials.gov Identifier:
    NCT01318694
    Other Study ID Numbers:
    • CDEB025A2301
    • 2010-022867-37
    First Posted:
    Mar 18, 2011
    Last Update Posted:
    Sep 30, 2016
    Last Verified:
    Aug 1, 2016