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A Study to Compare CNTO 328 (Anti-IL-6 Monoclonal Antibody) and VELCADE-Melphalan-Prednisone (VMP) With VMP Alone in Previously Untreated Multiple Myeloma Patients

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00911859
Collaborator
(none)
118
Enrollment
37
Locations
3
Arms
46
Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate safety and effectiveness of CNTO 328 (siltuximab) when it is administered together with velcade-melphalan-prednisone (VMP) in comparison with VMP alone in participants with multiple myeloma (a type of cancer that affects the blood and bone marrow).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The study will be conducted in 2 parts (Part 1 and Part 2) and will consist of screening period up to 2 weeks; treatment period; maintenance period (CNTO 328 hereafter referred to as siltuximab) for a maximum of 18 months and follow up period until the study ends. Part 1 is an open-label (all people know the identity of the intervention), single group safety lead-in part to evaluate the safety of siltuximab. Approximately 12 patients will be treated with siltuximab in combination with VMP. If the safety profile of the combination is acceptable, the study will proceed to Part 2. Part 2 is a randomized (the study medication is assigned by chance), open-label, 2-arm (Arm A: siltuximab + VMP; Arm B: VMP alone) study. Approximately 104 patients will be equally randomized, followed by a maintenance period with siltuximab in particiants in Arm A who achieve a partial response (PR) or better. Particiants in both parts of the study will be treated up to a maximum of nine 6-week cycles provided there is no evidence of disease progression, unacceptable toxicity, or withdrawal from treatment. Study medication will be continued for at least 2 additional cycles after confirmation of complete response, and preferably for the full 9 cycles of the treatment period. Participants who will be receiving maintenance treatment after the 12-month effectiveness analysis may continue to receive treatment with siltuximab only after careful consideration by the treating physician and on evidence of clinical benefit and in the absence of unwarranted toxicities. Safety assessments will include evaluation of adverse events, clinical laboratory tests, eastern cooperative oncology group performance status, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
118 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-Label, Phase 2 Study of CNTO 328 (Anti-IL-6 Monoclonal Antibody) and VELCADE-Melphalan-Prednisone Compared With VELCADE-Melphalan-Prednisone for the Treatment of Previously Untreated Multiple Myeloma
Study Start Date :
Jun 1, 2009
Actual Primary Completion Date :
Apr 1, 2013
Actual Study Completion Date :
Apr 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: VMP+Siltuximab 11 mg/kg

Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP (Velcade+Melphalan+Prednisone). Velcade 1.3 mg/m2 will be administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 will be taken orally (by mouth).

Drug: Siltuximab11 mg/kg
Participants will receive siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks in Part 1.
Other Names:
  • CNTO 328

    • Drug: Velcade (bortezomib)
    Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert in Part 1.
    Other Names:
  • bortezomib

    • Drug: Melphalan
    Participants will take melphalan 9 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.

    Drug: Prednisone
    Participants will take prednisone 60 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.
    Experimental: Part 2, Arm A: VMP+Siltuximab 8.3 mg/kg or 11 mg/kg

    Siltuximab 8.3 mg/kg or 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. Velcade 1.3 mg/m2 will be administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 will be taken orally

    Drug: Siltuximab 8.3 mg/kg or 11 mg/kg
    Participants will receive siltuximab 8.3 mg/kg or 11 mg/kg as a 1-hour intravenous infusion every 3 weeks for 9 cycles of treatment in Part 2, Arm A and in maintenance period.
    Other Names:
  • CNTO 328

    • Drug: Velcade (bortezomib)
    Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection for 9 cycles of the treatment period in Part 2. It will be administered twice weekly for first 4 cycles (on Days 1, 4, 8, 11, 22, 25, 29, and 32, followed by a 10-day rest period) and once weekly for next 5 cycles (on Days 1, 8, 22, and 29, followed by a 13-day rest period)
    Other Names:
  • bortezomib

    • Drug: Melphalan
    Participants will receive melphalan according to currently approved package inserts. Melphalan 9 mg/m2 will be administered orally for 9 cycles of treatment period in Part 2, Arm A.

    Drug: Prednisone
    Participants will take prednisone 60 mg/m2 orally for 9 cycles of treatment period in Part 2, Arm A.
    Active Comparator: Part 2, Arm B: VMP

    Velcade 1.3 mg/m2 will be administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 will be taken orally

    Drug: Velcade (bortezomib)
    Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert.
    Other Names:
  • bortezomib

    • Drug: Melphalan
    Participants will take melphalan 9 mg/m2 orally according to currently approved package insert.

    Drug: Prednisone
    Participants will take prednisone 60 mg/m2 orally according to the package insert.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Who Achieved Complete Response (CR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria [Up to disease progression, approximately 3 years]

      CR was assessed using EMBT criteria: disappearance of the original monoclonal paraprotein from the blood and urine on at least 2 determinations for a minimum of 6 weeks by immunofixation studies, <5% plasma cells in the bone marrow on at least 1 determination, if skeletal survey is available: no increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response), disappearance of soft tissue plasmacytomas for at least 6 weeks.

    Secondary Outcome Measures

    1. Percentage of Participants Who Achieved Overall Response ie, Complete Response (CR) or Partial Response (PR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria [Up to disease progression, approximately 3 years]

      CR or PR was assessed using EBMT criteria. CR: disappearance of the original monoclonal paraprotein from the blood and urine on at least 2 determinations for a minimum of 6 weeks by immunofixation studies, <5% plasma cells in the bone marrow on at least 1 determination, if skeletal survey is available: no increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response), disappearance of soft tissue plasmacytomas for at least 6 weeks; PR: >=50% reduction in the level of serum monoclonal paraprotein for at least 2 determinations 6 weeks apart, if present, reduction in 24-hour urinary light chain excretion by either >=90% or to <200 mg for at least 2 determinations 6 weeks apart, >=50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least 6 weeks, if skeletal survey is available: no increase in size or number of lytic bone lesions

    2. Percentage of Participants Who Achieved Stringent Complete Response (sCR) - International Myeloma Working Group (IMWG) Criteria [Up to disease progression, approximately 3 years]

      sCR was assesses by IMWG Criteria: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, <=5% plasma cells in bone marrow, normal free light chain ratio, absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. sCR is a CR that has been confirmed by immunofixation + free light chain assay + either bone marrow immunohistochemistry or immunofluorescence

    3. Progression-Free Survival (PFS) [From the date of randomization until disease progression or death, whichever occurred first, as assessed up to the last efficacy assessment for disease progression (approximately 3 years)]

      PFS was defined as the time between randomization and either disease progression or death, whichever occurred first.

    4. 1-year Progression-Free Survival (PFS) Rate [1 year]

      The 1-year PFS rate was defined as the percentage of participants surviving 1 year after randomization without disease progression or death.

    5. Duration of Response (DOR) [From the date participants achieved CR or PR to either date for disease progression (including relapse from CR) or the censoring date for progressive disease, as assessed Up to 30 days after last dose of study medication]

      DOR was defined as length from the earliest date a participant achieved a complete response (CR) or partial response (PR) to either date for disease progression (including relapse from CR) or the censoring date for progressive disease. Responders without disease progression were censored at the last efficacy assessment for disease progression.

    6. 1-year Survival Rate [1 year]

      Percentage of participants who are alive at the end of year 1 after randomization

    7. Overall Survival [From the date of randomization till the date of death, as assessed up to the end of study (approximately 3 years)]

      Overall survival is defined as the time interval in days between the date of randomization and the participant's death from any cause.

    8. Change From Baseline to Cycle 9 in Global Health Status/Quality of Life Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) [Baseline (Day 1 predose) and Cycle 9 (Week 54)]

      Global health status/quality of life is a subscale of the EORTC QOL C30, which comprises two questions related to overall health/quality of life during the past week. The raw score to each question ranged from 1 (very poor) to 7 (excellent). The raw mean score of health status/quality of life subscale is calculated for each participant and a linear transformation applied to standardize the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") health and quality of life.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Confirmed diagnosis of previously untreated multiple myeloma and not a candidate for high dose chemotherapy with stem cell transplantation

    • Eastern cooperative oncology group performance status score of less than or equal to 2

    • Measurable secretory disease, defined as either serum monoclonal paraprotein greater than or equal to 1 g/dL or urine monoclonal protein greater than 200 mg/24 hours

    • Adequate laboratory results that will be confirmed by a study physician

    • Agrees to protocol-defined use of effective contraception

    Exclusion Criteria:

    • Diagnosed with primary amyloidosis, asymptomatic or smoldering multiple myeloma or monoclonal gammopathy of undetermined significance

    • Diagnosed with Waldenstrom's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions

    • Received prior or current systemic therapy or stem cell transplantation for multiple myeloma

    • Peripheral neuropathy or neuropathic pain (Grade 2 or higher)

    • Received radiation therapy, plasmapheresis or surgery within 14 days

    • Transplanted solid organ, with the exception of a corneal transplant

    • Serious concurrent illness or history of uncontrolled heart disease

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Boston Massachusetts United States
    2 Chapel Hill North Carolina United States
    3 Philadelphia Pennsylvania United States
    4 Houston Texas United States
    5 Adelaide Australia
    6 Melbourne Australia
    7 Bordeaux Cedex France
    8 Montpellier France
    9 Strasbourg France
    10 Ahmedabad India
    11 Calicut India
    12 Hyderabad N/A India
    13 Jaipur India
    14 Mumbai India
    15 Afula Israel
    16 Haifa Israel
    17 Jerusalem Israel
    18 Petah Tikva Israel
    19 Ramat-Gan Israel
    20 Seoul Korea, Republic of
    21 Bialystok Poland
    22 Chorzów Poland
    23 Gdynia Poland
    24 Lodz Poland
    25 Wroclaw Poland
    26 Baia Mare Romania
    27 Brasov Romania
    28 Iasi Romania
    29 Arkhangelsk Russian Federation
    30 Moscow N/A Russian Federation
    31 Nizhni Novgorod Russian Federation
    32 St. Petersburg Russian Federation
    33 Singapore Singapore
    34 Barcelona Spain
    35 Madrid Spain
    36 Murcia N/A Spain
    37 Salamanca Spain

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

    • Study Director: Janssen Research & Development L.L.C Clinical Trial, Janssen Research & Development L.L.C

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT00911859
    Other Study ID Numbers:
    • CR015901
    • CNTO328MMY2001
    • 2008-007157-12
    • NCT01710241
    First Posted:
    Jun 2, 2009
    Last Update Posted:
    Nov 18, 2014
    Last Verified:
    Nov 1, 2014
    Keywords provided by Janssen Research & Development, LLC
    Multiple Myeloma
    CNTO328
    Interleukin-6 (IL-6)
    Monoclonal antibody
    Anti-IL-6 monoclonal antibody
    Bortezomib
    Velcade
    Melphalan
    Prednisone
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Prednisone
    Bortezomib
    Melphalan
    Siltuximab
    Antibodies, Monoclonal

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 40 centers in 12 countries: Australia; France; India; Israel; Italy; Poland; Romania; Russian Federation; Singapore; South Korea; Spain; and the United States.
    Pre-assignment Detail In Part 2, 105 participants received treatment (VMP: 53 and VMP+Siltuximab: 52). In the VMP+Siltuximab arm, 21 participants who achieved partial response or better entered the maintenance period and received only Siltuximab for 18 months, or until disease progression, unacceptable toxicity, or withdrawal from treatment, whichever occurred first.
    Arm/Group Title Part 1: VMP + Siltuximab Part 2: VMP Part 2: VMP + Siltuximab
    Arm/Group Description Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Period Title: Treatment Period
    STARTED 12 54 52
    Received Treatment 12 53 52
    COMPLETED 4 33 27
    NOT COMPLETED 8 21 25
    Period Title: Treatment Period
    STARTED 0 0 21
    COMPLETED 0 0 0
    NOT COMPLETED 0 0 21
    Period Title: Treatment Period
    STARTED 12 53 52
    COMPLETED 1 7 11
    NOT COMPLETED 11 46 41

    Baseline Characteristics

    Arm/Group Title Part 1: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Total
    Arm/Group Description Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Total of all reporting groups
    Overall Participants 12 54 52 118
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    73.6
    (6.3)
    70.3
    (7.27)
    71.6
    (4.76)
    71.2
    (6.21)
    Sex: Female, Male (Count of Participants)
    Female
    7
    58.3%
    30
    55.6%
    29
    55.8%
    66
    55.9%
    Male
    5
    41.7%
    24
    44.4%
    23
    44.2%
    52
    44.1%
    Region of Enrollment (participants) [Number]
    AUSTRALIA
    0
    0%
    2
    3.7%
    2
    3.8%
    4
    3.4%
    FRANCE
    0
    0%
    5
    9.3%
    2
    3.8%
    7
    5.9%
    INDIA
    0
    0%
    3
    5.6%
    1
    1.9%
    4
    3.4%
    ISRAEL
    0
    0%
    7
    13%
    5
    9.6%
    12
    10.2%
    ITALY
    0
    0%
    2
    3.7%
    2
    3.8%
    4
    3.4%
    POLAND
    0
    0%
    5
    9.3%
    11
    21.2%
    16
    13.6%
    ROMANIA
    0
    0%
    2
    3.7%
    0
    0%
    2
    1.7%
    RUSSIAN FEDERATION
    0
    0%
    10
    18.5%
    10
    19.2%
    20
    16.9%
    SINGAPORE
    0
    0%
    3
    5.6%
    2
    3.8%
    5
    4.2%
    SOUTH KOREA
    0
    0%
    7
    13%
    8
    15.4%
    15
    12.7%
    SPAIN
    12
    100%
    5
    9.3%
    7
    13.5%
    24
    20.3%
    UNITED STATES
    0
    0%
    3
    5.6%
    2
    3.8%
    5
    4.2%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Who Achieved Complete Response (CR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria
    Description CR was assessed using EMBT criteria: disappearance of the original monoclonal paraprotein from the blood and urine on at least 2 determinations for a minimum of 6 weeks by immunofixation studies, <5% plasma cells in the bone marrow on at least 1 determination, if skeletal survey is available: no increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response), disappearance of soft tissue plasmacytomas for at least 6 weeks.
    Time Frame Up to disease progression, approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population: Participants who had a confirmed diagnosis of multiple myeloma and measurable disease according to the EBMT criteria were evaluated for disease response. Also, participants must have received at least 1 administration of study medication and have at least 1 post-baseline disease assessment.
    Arm/Group Title Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab
    Arm/Group Description Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Measure Participants 49 49
    Number [Percentage of participants]
    22.4
    186.7%
    26.5
    49.1%
    2. Secondary Outcome
    Title Percentage of Participants Who Achieved Overall Response ie, Complete Response (CR) or Partial Response (PR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria
    Description CR or PR was assessed using EBMT criteria. CR: disappearance of the original monoclonal paraprotein from the blood and urine on at least 2 determinations for a minimum of 6 weeks by immunofixation studies, <5% plasma cells in the bone marrow on at least 1 determination, if skeletal survey is available: no increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response), disappearance of soft tissue plasmacytomas for at least 6 weeks; PR: >=50% reduction in the level of serum monoclonal paraprotein for at least 2 determinations 6 weeks apart, if present, reduction in 24-hour urinary light chain excretion by either >=90% or to <200 mg for at least 2 determinations 6 weeks apart, >=50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least 6 weeks, if skeletal survey is available: no increase in size or number of lytic bone lesions
    Time Frame Up to disease progression, approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population: Participants who had a confirmed diagnosis of multiple myeloma and measurable disease according to the EBMT criteria were evaluated for disease response. Also, participants must have received at least 1 administration of study medication and have at least 1 post-baseline disease assessment.
    Arm/Group Title Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab
    Arm/Group Description Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Measure Participants 49 49
    Number [Percentage of participants]
    79.6
    663.3%
    87.8
    162.6%
    3. Secondary Outcome
    Title Percentage of Participants Who Achieved Stringent Complete Response (sCR) - International Myeloma Working Group (IMWG) Criteria
    Description sCR was assesses by IMWG Criteria: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, <=5% plasma cells in bone marrow, normal free light chain ratio, absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. sCR is a CR that has been confirmed by immunofixation + free light chain assay + either bone marrow immunohistochemistry or immunofluorescence
    Time Frame Up to disease progression, approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population: Participants who had a confirmed diagnosis of multiple myeloma and measurable disease according to the EBMT criteria were evaluated for disease response. Also, participants must have received at least 1 administration of study medication and have at least 1 post-baseline disease assessment.
    Arm/Group Title Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab
    Arm/Group Description Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Measure Participants 49 49
    Number [Percentage of participants]
    6.1
    50.8%
    4.1
    7.6%
    4. Secondary Outcome
    Title Progression-Free Survival (PFS)
    Description PFS was defined as the time between randomization and either disease progression or death, whichever occurred first.
    Time Frame From the date of randomization until disease progression or death, whichever occurred first, as assessed up to the last efficacy assessment for disease progression (approximately 3 years)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population: all randomized participants.
    Arm/Group Title Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab
    Arm/Group Description Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Measure Participants 54 52
    Median (95% Confidence Interval) [Days]
    518
    519
    5. Secondary Outcome
    Title 1-year Progression-Free Survival (PFS) Rate
    Description The 1-year PFS rate was defined as the percentage of participants surviving 1 year after randomization without disease progression or death.
    Time Frame 1 year

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population: all randomized participants
    Arm/Group Title Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab
    Arm/Group Description Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Measure Participants 54 52
    Number [Percentage of participants]
    77.5
    645.8%
    72.1
    133.5%
    6. Secondary Outcome
    Title Duration of Response (DOR)
    Description DOR was defined as length from the earliest date a participant achieved a complete response (CR) or partial response (PR) to either date for disease progression (including relapse from CR) or the censoring date for progressive disease. Responders without disease progression were censored at the last efficacy assessment for disease progression.
    Time Frame From the date participants achieved CR or PR to either date for disease progression (including relapse from CR) or the censoring date for progressive disease, as assessed Up to 30 days after last dose of study medication

    Outcome Measure Data

    Analysis Population Description
    Included participants in the randomized population who achieved CR or PR.
    Arm/Group Title Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab
    Arm/Group Description Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Measure Participants 39 43
    Median (95% Confidence Interval) [Days]
    497
    583
    7. Secondary Outcome
    Title 1-year Survival Rate
    Description Percentage of participants who are alive at the end of year 1 after randomization
    Time Frame 1 year

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population: all randomized participants
    Arm/Group Title Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab
    Arm/Group Description Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Measure Participants 54 52
    Number [Percentage of participants]
    87.8
    731.7%
    87.5
    162%
    8. Secondary Outcome
    Title Overall Survival
    Description Overall survival is defined as the time interval in days between the date of randomization and the participant's death from any cause.
    Time Frame From the date of randomization till the date of death, as assessed up to the end of study (approximately 3 years)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population: all randomized participants.
    Arm/Group Title Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab
    Arm/Group Description Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Measure Participants 54 52
    Median (95% Confidence Interval) [Days]
    NA
    NA
    9. Secondary Outcome
    Title Change From Baseline to Cycle 9 in Global Health Status/Quality of Life Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30)
    Description Global health status/quality of life is a subscale of the EORTC QOL C30, which comprises two questions related to overall health/quality of life during the past week. The raw score to each question ranged from 1 (very poor) to 7 (excellent). The raw mean score of health status/quality of life subscale is calculated for each participant and a linear transformation applied to standardize the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") health and quality of life.
    Time Frame Baseline (Day 1 predose) and Cycle 9 (Week 54)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population: all randomized participants with evaluable data during baseline and Cycle 9
    Arm/Group Title Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab
    Arm/Group Description Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally.
    Measure Participants 31 25
    Mean (Standard Deviation) [Scores on a scale]
    14.78
    (25.250)
    8.33
    (31.088)

    Adverse Events

    Time Frame Up to 30 days after the last dose of study medication
    Adverse Event Reporting Description For Safety analyses all randomized participants who received at least 1 dose of study agents were analyzed. Data are presented for 117 participants in the treatment period (Part 1 and Part 2) and 21 participants who entered maintenance period (after achieving partial response or better in the Part 2 treatment period while receiving VPM+siltuximab)
    Arm/Group Title Part 1: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Part 2, Maintenance Period: Siltuximab
    Arm/Group Description Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. VMP: Velcade 1.3 mg/m2 was administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were taken orally. Siltuximab 8.3 mg/kg or 11 mg/kg as a 1-hour intravenous infusion every 3 weeks, during the maintenance period
    All Cause Mortality
    Part 1: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Part 2, Maintenance Period: Siltuximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Part 1: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Part 2, Maintenance Period: Siltuximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/12 (66.7%) 27/53 (50.9%) 30/52 (57.7%) 1/21 (4.8%)
    Blood and lymphatic system disorders
    Anaemia 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Neutropenia 0/12 (0%) 0/53 (0%) 3/52 (5.8%) 0/21 (0%)
    Thrombocytopenia 0/12 (0%) 2/53 (3.8%) 2/52 (3.8%) 0/21 (0%)
    Cardiac disorders
    Atrial Fibrillation 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Cardiac Arrest 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Cardiac Failure 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Cardiac Failure Acute 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Cardio-Respiratory Arrest 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Myocardial Infarction 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Endocrine disorders
    Steroid Withdrawal Syndrome 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Gastrointestinal disorders
    Abdominal Pain 0/12 (0%) 1/53 (1.9%) 2/52 (3.8%) 0/21 (0%)
    Diarrhoea 0/12 (0%) 4/53 (7.5%) 1/52 (1.9%) 0/21 (0%)
    Gastritis 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Haemorrhoidal Haemorrhage 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Ileus 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Ileus Paralytic 0/12 (0%) 1/53 (1.9%) 1/52 (1.9%) 0/21 (0%)
    Rectal Haemorrhage 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Upper Gastrointestinal Haemorrhage 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Vomiting 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    General disorders
    Adverse Drug Reaction 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Asthenia 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Pyrexia 1/12 (8.3%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Hepatobiliary disorders
    Hepatotoxicity 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Infections and infestations
    Bronchitis 0/12 (0%) 1/53 (1.9%) 1/52 (1.9%) 0/21 (0%)
    Bronchopneumonia 0/12 (0%) 3/53 (5.7%) 2/52 (3.8%) 0/21 (0%)
    Gastroenteritis 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Gastroenteritis Escherichia Coli 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    H1n1 Influenza 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Hepatitis B 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Lobar Pneumonia 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Parotitis 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Pneumonia 3/12 (25%) 5/53 (9.4%) 7/52 (13.5%) 0/21 (0%)
    Pneumonia Pneumococcal 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Respiratory Tract Infection 1/12 (8.3%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Septic Shock 1/12 (8.3%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Injury, poisoning and procedural complications
    Femur Fracture 0/12 (0%) 0/53 (0%) 2/52 (3.8%) 0/21 (0%)
    Hip Fracture 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Radius Fracture 0/12 (0%) 0/53 (0%) 0/52 (0%) 1/21 (4.8%)
    Spinal Compression Fracture 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Spinal Fracture 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Investigations
    Weight Decreased 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/12 (0%) 1/53 (1.9%) 1/52 (1.9%) 0/21 (0%)
    Hypercalcaemia 1/12 (8.3%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Hyperglycaemia 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Hyperkalaemia 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Hyperuricaemia 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Hypoglycaemia 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Hypokalaemia 0/12 (0%) 0/53 (0%) 2/52 (3.8%) 0/21 (0%)
    Hyponatraemia 0/12 (0%) 2/53 (3.8%) 2/52 (3.8%) 0/21 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Back Pain 1/12 (8.3%) 1/53 (1.9%) 1/52 (1.9%) 0/21 (0%)
    Bone Lesion 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Pathological Fracture 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma Pancreas 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Multiple Myeloma 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Myelodysplastic Syndrome 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Rectal Cancer 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Nervous system disorders
    Cerebral Ischaemia 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Cerebrovascular Accident 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Dizziness 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Encephalopathy 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Hypoglycaemic Encephalopathy 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Lacunar Infarction 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Metabolic Encephalopathy 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Syncope 0/12 (0%) 0/53 (0%) 2/52 (3.8%) 0/21 (0%)
    Psychiatric disorders
    Completed Suicide 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Depression 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Renal and urinary disorders
    Hydronephrosis 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Renal Failure 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Renal Failure Acute 0/12 (0%) 1/53 (1.9%) 3/52 (5.8%) 0/21 (0%)
    Renal Impairment 1/12 (8.3%) 1/53 (1.9%) 1/52 (1.9%) 0/21 (0%)
    Urinary Retention 0/12 (0%) 2/53 (3.8%) 0/52 (0%) 0/21 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Asthma 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Chronic Obstructive Pulmonary Disease 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Dyspnoea 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Pleural Effusion 1/12 (8.3%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Pulmonary Embolism 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Pulmonary Oedema 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Respiratory Failure 1/12 (8.3%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Status Asthmaticus 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Skin and subcutaneous tissue disorders
    Leukocytoclastic Vasculitis 0/12 (0%) 0/53 (0%) 1/52 (1.9%) 0/21 (0%)
    Vascular disorders
    Hypotension 0/12 (0%) 2/53 (3.8%) 0/52 (0%) 0/21 (0%)
    Hypovolaemic Shock 0/12 (0%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Other (Not Including Serious) Adverse Events
    Part 1: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Part 2: VMP (Velcade+Melphalan+Prednisone) Part 2: VMP (Velcade+Melphalan+Prednisone) + Siltuximab Part 2, Maintenance Period: Siltuximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/12 (100%) 51/53 (96.2%) 51/52 (98.1%) 15/21 (71.4%)
    Blood and lymphatic system disorders
    Anaemia 5/12 (41.7%) 19/53 (35.8%) 12/52 (23.1%) 2/21 (9.5%)
    Leukopenia 0/12 (0%) 5/53 (9.4%) 6/52 (11.5%) 0/21 (0%)
    Lymphopenia 0/12 (0%) 3/53 (5.7%) 4/52 (7.7%) 0/21 (0%)
    Neutropenia 11/12 (91.7%) 25/53 (47.2%) 34/52 (65.4%) 3/21 (14.3%)
    Thrombocytopenia 8/12 (66.7%) 21/53 (39.6%) 30/52 (57.7%) 5/21 (23.8%)
    Cardiac disorders
    Atrial Fibrillation 1/12 (8.3%) 2/53 (3.8%) 2/52 (3.8%) 0/21 (0%)
    Eye disorders
    Conjunctivitis 0/12 (0%) 2/53 (3.8%) 4/52 (7.7%) 0/21 (0%)
    Dry Eye 0/12 (0%) 4/53 (7.5%) 1/52 (1.9%) 0/21 (0%)
    Gastrointestinal disorders
    Abdominal Discomfort 0/12 (0%) 3/53 (5.7%) 2/52 (3.8%) 0/21 (0%)
    Abdominal Distension 0/12 (0%) 2/53 (3.8%) 3/52 (5.8%) 0/21 (0%)
    Abdominal Pain 1/12 (8.3%) 6/53 (11.3%) 4/52 (7.7%) 0/21 (0%)
    Abdominal Pain Upper 0/12 (0%) 4/53 (7.5%) 4/52 (7.7%) 0/21 (0%)
    Constipation 8/12 (66.7%) 16/53 (30.2%) 18/52 (34.6%) 2/21 (9.5%)
    Diarrhoea 7/12 (58.3%) 21/53 (39.6%) 18/52 (34.6%) 2/21 (9.5%)
    Dry Mouth 0/12 (0%) 0/53 (0%) 4/52 (7.7%) 0/21 (0%)
    Dyspepsia 0/12 (0%) 6/53 (11.3%) 3/52 (5.8%) 1/21 (4.8%)
    Gastritis 0/12 (0%) 3/53 (5.7%) 1/52 (1.9%) 1/21 (4.8%)
    Haemorrhoids 1/12 (8.3%) 2/53 (3.8%) 4/52 (7.7%) 0/21 (0%)
    Mouth Ulceration 1/12 (8.3%) 0/53 (0%) 2/52 (3.8%) 0/21 (0%)
    Nausea 4/12 (33.3%) 21/53 (39.6%) 16/52 (30.8%) 0/21 (0%)
    Stomatitis 1/12 (8.3%) 2/53 (3.8%) 1/52 (1.9%) 0/21 (0%)
    Vomiting 2/12 (16.7%) 15/53 (28.3%) 12/52 (23.1%) 1/21 (4.8%)
    General disorders
    Asthenia 10/12 (83.3%) 18/53 (34%) 10/52 (19.2%) 0/21 (0%)
    Chest Pain 0/12 (0%) 5/53 (9.4%) 6/52 (11.5%) 1/21 (4.8%)
    Chills 1/12 (8.3%) 3/53 (5.7%) 3/52 (5.8%) 0/21 (0%)
    Fatigue 0/12 (0%) 8/53 (15.1%) 12/52 (23.1%) 2/21 (9.5%)
    Malaise 1/12 (8.3%) 3/53 (5.7%) 0/52 (0%) 0/21 (0%)
    Mucosal Discolouration 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Oedema 2/12 (16.7%) 4/53 (7.5%) 0/52 (0%) 0/21 (0%)
    Oedema Peripheral 3/12 (25%) 4/53 (7.5%) 16/52 (30.8%) 0/21 (0%)
    Pain 0/12 (0%) 2/53 (3.8%) 3/52 (5.8%) 1/21 (4.8%)
    Pyrexia 1/12 (8.3%) 15/53 (28.3%) 9/52 (17.3%) 0/21 (0%)
    Spinal Pain 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Hepatobiliary disorders
    Hepatic Function Abnormal 1/12 (8.3%) 2/53 (3.8%) 6/52 (11.5%) 0/21 (0%)
    Hepatotoxicity 1/12 (8.3%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Jaundice 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Infections and infestations
    Bronchitis 0/12 (0%) 5/53 (9.4%) 6/52 (11.5%) 0/21 (0%)
    H1n1 Influenza 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Hordeolum 1/12 (8.3%) 3/53 (5.7%) 0/52 (0%) 0/21 (0%)
    Nasopharyngitis 3/12 (25%) 5/53 (9.4%) 4/52 (7.7%) 2/21 (9.5%)
    Nipple Infection 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Onychomycosis 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Oral Candidiasis 3/12 (25%) 3/53 (5.7%) 0/52 (0%) 0/21 (0%)
    Pharyngitis 1/12 (8.3%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Respiratory Tract Infection 2/12 (16.7%) 1/53 (1.9%) 3/52 (5.8%) 0/21 (0%)
    Respiratory Tract Infection Viral 0/12 (0%) 3/53 (5.7%) 0/52 (0%) 0/21 (0%)
    Sinusitis 0/12 (0%) 0/53 (0%) 3/52 (5.8%) 0/21 (0%)
    Upper Respiratory Tract Infection 3/12 (25%) 6/53 (11.3%) 5/52 (9.6%) 2/21 (9.5%)
    Urinary Tract Infection 1/12 (8.3%) 2/53 (3.8%) 5/52 (9.6%) 0/21 (0%)
    Injury, poisoning and procedural complications
    Limb Injury 0/12 (0%) 0/53 (0%) 0/52 (0%) 2/21 (9.5%)
    Investigations
    Weight Decreased 0/12 (0%) 6/53 (11.3%) 6/52 (11.5%) 2/21 (9.5%)
    Metabolism and nutrition disorders
    Decreased Appetite 4/12 (33.3%) 18/53 (34%) 9/52 (17.3%) 1/21 (4.8%)
    Enzyme Abnormality 0/12 (0%) 1/53 (1.9%) 4/52 (7.7%) 0/21 (0%)
    Fluid Retention 2/12 (16.7%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Hyperamylasaemia 0/12 (0%) 0/53 (0%) 3/52 (5.8%) 0/21 (0%)
    Hypercholesterolaemia 1/12 (8.3%) 2/53 (3.8%) 0/52 (0%) 0/21 (0%)
    Hyperglycaemia 1/12 (8.3%) 3/53 (5.7%) 2/52 (3.8%) 0/21 (0%)
    Hyperkalaemia 0/12 (0%) 1/53 (1.9%) 3/52 (5.8%) 0/21 (0%)
    Hypoalbuminaemia 0/12 (0%) 0/53 (0%) 3/52 (5.8%) 0/21 (0%)
    Hypocalcaemia 2/12 (16.7%) 2/53 (3.8%) 3/52 (5.8%) 0/21 (0%)
    Hypoglycaemia 0/12 (0%) 0/53 (0%) 4/52 (7.7%) 0/21 (0%)
    Hypokalaemia 4/12 (33.3%) 2/53 (3.8%) 7/52 (13.5%) 1/21 (4.8%)
    Hypomagnesaemia 1/12 (8.3%) 0/53 (0%) 4/52 (7.7%) 0/21 (0%)
    Hyponatraemia 0/12 (0%) 4/53 (7.5%) 4/52 (7.7%) 0/21 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/12 (0%) 6/53 (11.3%) 6/52 (11.5%) 0/21 (0%)
    Back Pain 2/12 (16.7%) 7/53 (13.2%) 9/52 (17.3%) 0/21 (0%)
    Bone Pain 1/12 (8.3%) 3/53 (5.7%) 6/52 (11.5%) 0/21 (0%)
    Muscular Weakness 1/12 (8.3%) 4/53 (7.5%) 3/52 (5.8%) 0/21 (0%)
    Musculoskeletal Chest Pain 0/12 (0%) 2/53 (3.8%) 4/52 (7.7%) 0/21 (0%)
    Musculoskeletal Pain 0/12 (0%) 3/53 (5.7%) 1/52 (1.9%) 3/21 (14.3%)
    Myalgia 0/12 (0%) 4/53 (7.5%) 2/52 (3.8%) 0/21 (0%)
    Neck Pain 1/12 (8.3%) 0/53 (0%) 1/52 (1.9%) 2/21 (9.5%)
    Pain in Extremity 2/12 (16.7%) 7/53 (13.2%) 10/52 (19.2%) 3/21 (14.3%)
    Nervous system disorders
    Dizziness 2/12 (16.7%) 9/53 (17%) 11/52 (21.2%) 1/21 (4.8%)
    Essential Tremor 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Headache 0/12 (0%) 3/53 (5.7%) 4/52 (7.7%) 1/21 (4.8%)
    Monoparesis 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Neuralgia 5/12 (41.7%) 16/53 (30.2%) 10/52 (19.2%) 0/21 (0%)
    Paraesthesia 0/12 (0%) 4/53 (7.5%) 4/52 (7.7%) 0/21 (0%)
    Peripheral Sensory Neuropathy 9/12 (75%) 34/53 (64.2%) 31/52 (59.6%) 1/21 (4.8%)
    Somnolence 1/12 (8.3%) 2/53 (3.8%) 1/52 (1.9%) 0/21 (0%)
    Syncope 0/12 (0%) 3/53 (5.7%) 2/52 (3.8%) 0/21 (0%)
    Tremor 1/12 (8.3%) 1/53 (1.9%) 1/52 (1.9%) 0/21 (0%)
    Psychiatric disorders
    Agitation 1/12 (8.3%) 1/53 (1.9%) 0/52 (0%) 0/21 (0%)
    Anxiety 2/12 (16.7%) 5/53 (9.4%) 4/52 (7.7%) 0/21 (0%)
    Confusional State 0/12 (0%) 3/53 (5.7%) 1/52 (1.9%) 0/21 (0%)
    Depression 2/12 (16.7%) 3/53 (5.7%) 3/52 (5.8%) 0/21 (0%)
    Hallucination 1/12 (8.3%) 0/53 (0%) 1/52 (1.9%) 1/21 (4.8%)
    Insomnia 3/12 (25%) 13/53 (24.5%) 10/52 (19.2%) 1/21 (4.8%)
    Renal and urinary disorders
    Dysuria 0/12 (0%) 2/53 (3.8%) 4/52 (7.7%) 0/21 (0%)
    Renal Impairment 0/12 (0%) 1/53 (1.9%) 6/52 (11.5%) 0/21 (0%)
    Reproductive system and breast disorders
    Pelvic Pain 0/12 (0%) 0/53 (0%) 3/52 (5.8%) 0/21 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/12 (16.7%) 10/53 (18.9%) 11/52 (21.2%) 1/21 (4.8%)
    Dyspnoea 1/12 (8.3%) 8/53 (15.1%) 6/52 (11.5%) 0/21 (0%)
    Epistaxis 1/12 (8.3%) 0/53 (0%) 3/52 (5.8%) 0/21 (0%)
    Nasal Congestion 0/12 (0%) 3/53 (5.7%) 2/52 (3.8%) 0/21 (0%)
    Productive Cough 0/12 (0%) 3/53 (5.7%) 4/52 (7.7%) 0/21 (0%)
    Rhinorrhoea 0/12 (0%) 3/53 (5.7%) 2/52 (3.8%) 0/21 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Erythema 0/12 (0%) 3/53 (5.7%) 2/52 (3.8%) 0/21 (0%)
    Pruritus 1/12 (8.3%) 5/53 (9.4%) 5/52 (9.6%) 0/21 (0%)
    Rash 1/12 (8.3%) 4/53 (7.5%) 7/52 (13.5%) 0/21 (0%)
    Scar 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Vascular disorders
    Haematoma 1/12 (8.3%) 0/53 (0%) 0/52 (0%) 0/21 (0%)
    Hypertension 1/12 (8.3%) 7/53 (13.2%) 4/52 (7.7%) 0/21 (0%)
    Hypotension 1/12 (8.3%) 2/53 (3.8%) 7/52 (13.5%) 1/21 (4.8%)
    Orthostatic Hypotension 2/12 (16.7%) 2/53 (3.8%) 3/52 (5.8%) 0/21 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Senior Director
    Organization Janssen R&D BE
    Phone
    Email ClinicalTrialDisclosure@its.jnj.com
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT00911859
    Other Study ID Numbers:
    • CR015901
    • CNTO328MMY2001
    • 2008-007157-12
    • NCT01710241
    First Posted:
    Jun 2, 2009
    Last Update Posted:
    Nov 18, 2014
    Last Verified:
    Nov 1, 2014