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Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis

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ClinicalTrials.gov Identifier: NCT02531633
Recruitment Status : Terminated (GSK decision to return rights to sirukumab to Janssen and discontinue sirukumab development in giant cell arteritis.)
First Posted : August 24, 2015
Results First Posted : May 31, 2019
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:

Sirukumab is a fully human anti-interleukin-6 (IL-6) immunoglobulin G1-kappa with a high affinity and specificity for binding to the human IL-6 molecule that may have therapeutic benefit in the treatment of giant cell arteritis (GCA) by interruption of multiple pathogenic pathways. Sirukumab inhibits IL-6-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation, resulting in the inhibition of the biological effect of IL-6. This study will evaluate the efficacy and safety of sirukumab to characterize the benefit-to-risk profile of sirukumab in the treatment of active GCA. The study will be conducted in 2 distinct parts (Part A and Part B) and consists of the following phases: Screening phase, Part A: 52-week double-blind treatment phase, Part B: 104-week extension phase with the option to receive open-label sirukumab based on disease status and a 16-week follow-up phase if applicable.

Approximately 204 subjects with a diagnosis of GCA and active disease within 6 weeks of baseline will be randomized into Part A, the 52-week double-blind treatment phase, to receive one of two doses of sirukumab or placebo, each in addition to a pre-specified prednisone taper. The efficacy and safety of sirukumab in sustaining remission will be assessed at Week 52. Subjects completing Part A of the study will be eligible to enter Part B, the 104-week extension phase, designed to investigate the long-term maintenance of remission and safety following cessation of sirukumab treatment and to assess long-term corticosteroid use. Subjects with active GCA at the end of Part A or those with new onset of GCA flare during the first 52 weeks of Part B will be eligible to receive open-label sirukumab. Subjects will need to have follow-up safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable only for those who are withdrawn prematurely from the study or whose open-label sirukumab treatment in Part B completes after Week 88.


Condition or disease Intervention/treatment Phase
Giant Cell Arteritis Drug: Sirukumab Drug: Placebo to match sirukumab Drug: Prednisone Drug: Placebo to match prednisone Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 161 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Patients With Giant Cell Arteritis
Actual Study Start Date : October 16, 2015
Actual Primary Completion Date : March 21, 2018
Actual Study Completion Date : March 21, 2018


Arm Intervention/treatment
Experimental: Part A: Sirukumab, Dose 1+prednisone (6-month taper)
Subjects will receive blinded sirukumab 100 mg subcutaneously (SC) every 2 weeks (q2w) for 52 weeks plus a pre-specified maximum of 6-month oral prednisone taper regimen.
Drug: Sirukumab
Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.

Drug: Prednisone
Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).

Drug: Placebo to match prednisone
Placebo to match prednisone will be provided as tablets.

Experimental: Part A: Sirukumab, Dose 1+prednisone (3-month taper)
Subjects will receive blinded sirukumab 100 mg SC q2w for 52 weeks plus a pre-specified maximum of 3-month oral prednisone taper regimen.
Drug: Sirukumab
Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.

Drug: Prednisone
Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).

Drug: Placebo to match prednisone
Placebo to match prednisone will be provided as tablets.

Experimental: Part A: Sirukumab, Dose 2+prednisone (6-month taper)
Subjects will receive blinded sirukumab 50 mg SC every 4 weeks (q4w) for 52 weeks plus a pre-specified maximum of 6-month oral prednisone taper regimen.
Drug: Sirukumab
Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.

Drug: Prednisone
Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).

Drug: Placebo to match prednisone
Placebo to match prednisone will be provided as tablets.

Placebo Comparator: Part A:Placebo to match sirutkumab+prednisone (6-month taper)
Subjects will receive blinded placebo to match sirutkumab q2w for 52 weeks plus a pre-specified maximum of 6-month oral prednisone taper regimen.
Drug: Placebo to match sirukumab
Placebo to match sirukumab will be provided as 1.0 mL PFS fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.

Drug: Prednisone
Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).

Drug: Placebo to match prednisone
Placebo to match prednisone will be provided as tablets.

Placebo Comparator: Part A:Placebo to match sirukumab+prednisone (12-month taper)
Subjects will receive blinded placebo to match sirutkumab q2w for 52 weeks plus a pre-specified maximum of 12-month oral prednisone taper regimen.
Drug: Placebo to match sirukumab
Placebo to match sirukumab will be provided as 1.0 mL PFS fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.

Drug: Prednisone
Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).

Drug: Placebo to match prednisone
Placebo to match prednisone will be provided as tablets.

Experimental: Part B:Open-label sirukumab 100 mg SC (if applicable)
Subjects completing Part A will receive open label 100 mg SC q2w for a maximum of 52 weeks based on remission status and disease activity at the primary 52-week endpoint or prednisone tapering status of subject during Part A. Methotrexate will be provided to subjects, alone or in addition to sirukumab treatment during Part B, based on the discretion of the investigator.
Drug: Sirukumab
Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.




Primary Outcome Measures :
  1. Part A: Number of Participants in Sustained Remission at Week 52 [ Time Frame: Week 52 ]
    Sustained remission was defined as having achieved all of the following: 1) remission at Week 12, 2) absence of disease flare Week 12 through Week 52, 3) completion of the assigned prednisone taper, and 4) no requirement for rescue therapy through Week 52. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of erythrocyte sedimentation rate (ESR) [<30 millimeters per hour] and C-reactive Protein (CRP) [<1 milligram/deciliter]) and flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP. Data for number of participants in sustained remission at Week 52 is presented. Only those participants who completed Week 52 visit or withdrew before 10 Oct 2017 were included in the analysis.


Secondary Outcome Measures :
  1. Part B: Number of Participants Who Remained in Sustained Remission Without Requirement for Rescue Therapy or Treatment Change at Week 24 [ Time Frame: Week 24 ]
    Participants who remained in sustained remission without requirement for rescue therapy or treatment change at each scheduled visit of Part B were defined as participants having achieved all of the following criteria: 1. Participants in sustained remission at the Week 52 visit of Part A, 2. Absence of disease flare, 3. No requirement for rescue therapy at any time through Week 24 of Part B, 4. No requirement for treatment change at any time through Week 24 of Part B. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of ESR [<30 millimeters per hour] and CRP [<1 milligram/deciliter]) and flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP.

  2. Part A: Cumulative Prednisone Dose Over Time [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    Cumulative prednisone is the dose from the taper (both open-label and blinded) as well as from the corticosteroid rescue therapies. Cumulative dose at the specified Week was derived as the sum of all the doses from Baseline to the specified Week at each visit was calculated based on the number of participants who attended that visit. For the main analysis of cumulative prednisone dose over time. Data for Prednisone Dose- Study Drug and Prednisone Equivalent Concomitant Therapy for part A is presented. ITT population and the number of participants included at specific time points were based on the participants who attended a scheduled or unscheduled visit mapped to that time point and received a total prednisone dose greater than 0 mg.

  3. Part B: Number of Participants in Sustained Remission Over Time [ Time Frame: Weeks 4, 8 and 12 ]
    Sustained remission was defined as having achieved all of the following: 1) remission at Week 12 (absence of signs and symptoms of GCA and normalization of ESR and CRP), 2) absence of disease flare Week 12 through Week 52 with or without elevations in ESR and/or CRP, 3) completion of the assigned prednisone taper, and 4) no requirement for rescue therapy through Week 52. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of ESR [<30millimeters per hour] and CRP [<1milligram/deciliter]) and Flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP. Data for number of participants in sustained remission over time for Part B is presented. Only participants who were in sustained remission at Week 52 of Part A, who Completed the Week X Visit of Part B or who Withdraw before 10th of October 2017 were included in the analysis.

  4. Part A: Time to First Disease Flare After Clinical Remission [ Time Frame: Week 52 ]
    Clinical remission was defined as absence of clinical signs and symptoms of GCA, which was determined by a lack of flare for the participant. If a participant had a flare, they had one or more signs and symptoms, and therefore are not considered as being in clinical remission. Time to first disease flare (days) was calculated as (Date of First Flare - Date of Clinical Remission + 1 day). Data for Time to first disease flare after clinical remission for part A is presented.

  5. Part B: Time to First Disease Flare for Participants in Sustained Remission [ Time Frame: Week 52 ]
    Clinical remission was defined as absence of clinical signs and symptoms of GCA. If a participant had a flare, they had one or more signs and symptoms, and therefore are not considered as being in clinical remission. Time to event (days) is defined as the duration in days from the date of the Week 52 visit of Part A to the start date of Event (Date of First Flare - Date of Week 52 visit of Part A + 1). Data for Time to first disease flare after clinical remission for part B is presented.

  6. Part A: Number of Disease Flares Over Time [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    This summarizes disease flares over time with no adjustment for exposure to study drugs, calculated by taking the last visit before a participant withdrew and then counting the number of participants with at least 1 flare up to that point and summing up the total number of flares experienced by each of these participants; participants who did not reach Week 2 were not included in this analysis. Data for number of disease flares per participant over time for part A were presented.

  7. Part A: Number of Participants With at Least One Hospitalization for Disease Flare [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    Number of participants with at least one hospitalization for disease flare at a given visit is the number of participants with at least one hospitalization for disease flare between first SC IP intake and the day of the given visit. Data for participants requiring at least one hospitalization for disease flare for part A is presented.

  8. Part A: Number of Hospitalizations for Disease Flare Over Time [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    Number of hospitalizations for disease flare at given visit is the number of hospitalizations for disease flare between first SC IP intake and the day of the of the given visit.. Data for number of hospitalizations for disease flare over time for part A was presented.

  9. Part A: Mean 36-item Short Form Health Survey Version 2 (SF-36 v2) Acute Score Over Time [ Time Frame: Baseline (Week 0), Weeks 12, 24, 36, 52 ]
    SF-36v2 acute health survey questionnaire consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for Physical Component Summary (PCS), Mental Component Summary (MCS) scores was presented.

  10. Part A: Mean EuroQol - 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score Over Time [ Time Frame: Baseline (Week 0) and Weeks 12, 24, 36, 52 ]
    EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score).

  11. Part A: Mean EQ-5D-5L Visual Analogue Scale (VAS) Over Time [ Time Frame: Baseline (Week 0) and Weeks 12, 24, 36, 52 ]
    EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of the 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. The index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for the conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1 (best score). The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 'Best imaginable health state' and 'Worst imaginable health state'.

  12. Part A: Mean Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-Fatigue) Scores Over Time [ Time Frame: Baseline (Week 0), Weeks 12, 24, 36, 52 ]
    The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Each negatively-worded item response was recoded so that 0 is a bad response and 4 is good response. All responses were added with equal weight to obtain the total score. The total score was calculated as the sum of all the individual items after recoding some of the items.

  13. Part A: Mean Pain Numeric Rating Scale (NRS) Scores Over Time [ Time Frame: Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain on a 11-point numeric rating scale ranging from 0, "no pain" to 10, "the worst pain imaginable". Data for NRS scores over time for part A is reported.

  14. Part A: Mean Health Assessment Questionnaire - Disability Index (HAQDI) Score Over Time [ Time Frame: Baseline (Week 0) and Weeks 12, 24, 36 and 52 ]
    Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing "no difficulty" (0), "some difficulty" (1), "much difficulty" (2), and "unable to do" (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability.

  15. Part A: Number of Participants With Patient Global Impression of Change (PGIC) Score Over Time [ Time Frame: Weeks 12, 24 and 52 ]
    Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category.

  16. Part A: Mean Patient Global Assessment of Disease Activity (PtGA) Score Over Time [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS) of 10 centimeter (cm) ranging from 0 ("very well) to 10 ("very poor").

  17. Part A: Mean Physician Global Assessment of Disease Activity (PhGA) Score Over Time [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    The Physician's Global Assessments of Disease Activity was recorded on a VAS of 10 cm ranging from 0 ("none") to 10 ("extremely active").

  18. Part A: Change From Baseline in Serum C Reactive Protein (CRP) Over Time [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    Blood samples were collected for analysis of CRP. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for Change from Baseline in serum CRP over time for part A was reported. The Safety set comprised of all randomized participants who received at least 1 dose of SC IP.

  19. Part A: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Over Time [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    Blood samples were collected for analysis of ESR. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for Change from Baseline in ESR over time for part A was reported.

  20. Part A: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs) and Corticosteroid Related AEs [ Time Frame: Up to 52 weeks ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs have been reported.

  21. Part A: Change From Baseline in : Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: Baseline (Week 0), Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    SBP and DBP were measured in semi-supine position after 5 minutes rest at indicated time points. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  22. Part A: Change From Baseline in Pulse Rate [ Time Frame: Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Pulse rate was measured in semi-supine position after 5 minutes rest at Baseline and up to 52 weeks. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  23. Part A: Change From Baseline in Temperature [ Time Frame: Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Temperature was measured in semi-supine position after 5 minutes rest at Baseline and up to 52 weeks. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  24. Part A: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets [ Time Frame: Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  25. Part A: Change From Baseline in Hematology Parameters- Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin [ Time Frame: Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  26. Part A: Change From Baseline in Hematology Parameter-Hematocrit [ Time Frame: Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  27. Part A: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume [ Time Frame: Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Volume. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  28. Part A:Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin [ Time Frame: Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  29. Part A:Change From Baseline in Hematology Parameter- Erythrocytes [ Time Frame: Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  30. Part A: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea [ Time Frame: Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea . Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  31. Part A: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  32. Part A: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  33. Part A: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Blood samples were collected to analyze the chemistry parameters including bilirubin, creatinine, direct bilirubin and indirect bilirubin. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

  34. Part A: Mean Serum Concentrations of Sirukumab [ Time Frame: Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 44 and 52 ]
    Blood samples for Pharmacokinetic analysis of sirukumab serum concentrations were planned to be collected at specified time points.

  35. Part A: Mean Serum Anti-sirukumab Antibodies [ Time Frame: Baseline (Week 0) and up to 52 weeks ]
    Blood samples for Pharmacokinetic analysis of Serum anti-sirukumab antibodies were planned to be collected at specified time points.

  36. Part A: Change From Baseline in Free and Total Interleukin-6 (IL-6) Over Time [ Time Frame: Baseline (Week 0) and up to 52 weeks ]
    Blood samples for Pharmacodynamic analysis were planned but not collected due to early termination of study.

  37. Part B: Number of Participants With AEs, SAEs and Corticosteroid Related AEs Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Up to 120 weeks ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs for part B have been reported.

  38. Part B: Number of Participants With AEs, SAEs and Corticosteroid Related AEs Who Never Received 100mg OL Sirukumab in Part B [ Time Frame: Up to 120 weeks ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs for part B have been reported.

  39. Part B: Change From Baseline in SBP and DBP for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120) ]
    SBP and DBP were measured in semi-supine position after 5 minutes rest for the participant. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  40. Part B: Change From Baseline in SBP and DBP for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120) ]
    SBP and DBP were measured in semi-supine position after 5 minutes rest for the participant. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  41. Part B: Change From Baseline in Pulse Rate for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120) ]
    Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  42. Part B: Change From Baseline in Pulse Rate for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120) ]
    Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab is presented.

  43. Part B: Change From Baseline in Temperature for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120) ]
    Temperature was measured in semi-supine position after 5 minutes rest.. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  44. Part B: Change From Baseline in Temperature for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120) ]
    Temperature was measured in semi-supine position after 5 minutes rest.. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  45. Part B: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters.Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  46. Part B: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters.Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  47. Part B: Change From Baseline in Hematology Parameters- MCHC and Hemoglobin for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  48. Part B: Change From Baseline in Hematology Parameters- MCHC and Hemoglobin for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  49. Part B: Change From Baseline in Hematology Parameter-Hematocrit for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  50. Part B: Change From Baseline in Hematology Parameter-Hematocrit for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  51. Part B: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Volume. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  52. Part B: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  53. Part B: Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented.

  54. Part B: Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  55. Part B: Change From Baseline in Hematology Parameter- Erythrocytes for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented.

  56. Part B: Change From Baseline in Hematology Parameter- Erythrocytes for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  57. Part B: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented.

  58. Part B: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  59. Part B: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  60. Part B: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  61. Part B: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP and AST for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  62. Part B: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP and AST for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented

  63. Part B: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

  64. Part B: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 ]
    Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

  65. Part B: Cumulative Prednisone Dose Over Time for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B [ Time Frame: Weeks 2, 4, 8, 12, 14, 16, 24, 28, 32 and 38 ]
    Cumulative prednisone dose is the cumulative doses taken from start of Part B. The cumulative prednisone dose at each visit was calculated based on the number of participants who attended that visit. Data for participants who received at least one dose of 100mg open label Sirukumab was presented.

  66. Part B: Cumulative Prednisone Dose Over Time for Participants Who Never Received 100 mg Open Label Sirukumab in Part B [ Time Frame: Weeks 2, 4, 8, 12, 14, 16, 24, 28, 32 and 38 ]
    Cumulative prednisone dose is the cumulative doses taken from start of Part B. The cumulative prednisone dose at each visit was calculated based on the number of participants who attended that visit. Data for participants who never received 100 mg open label Sirukumab has been presented.

  67. Part B: Number of Disease Flares Over Time [ Time Frame: Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    This summarizes disease flares over time with no adjustment for exposure to study drugs, calculated by taking the last visit before a participant withdrew and then counting the number of participants with at least 1 flare up to that point and summing up the total number of flares experienced by each of these participants. Data for number of disease flares per participant over time for part B were presented.

  68. Part B: Number of Participants Requiring at Least One Hospitalization for Disease Flare [ Time Frame: Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Number of participants with at least one flare at a given visit was the number of participants with at least one flare between first SC IP intake and the day of the given visit. The hospitalizations for disease flare were planned to be identified through the adjudication of adverse events of special interest, and include events from the category: "Severe Flare including Hospitalizations". Data for participants requiring hospitalizations for disease flare for part B was not available due to early termination of study.

  69. Part B: Number of Hospitalizations for Disease Flare Over Time [ Time Frame: Up to Week 104 ]
    Number of participants with at least one flare at a given visit was the number of participants with at least one flare between first SC IP intake and the day of the given visit. The hospitalizations for disease flare were planned to be identified through the adjudication of adverse events of special interest, and include events from the category: "Severe Flare including Hospitalizations". Data for participants requiring hospitalizations for disease flare for part B was not available due to early termination of study.

  70. Part B: Change From Baseline in 36-item SF-36 v2 Acute Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0), Day 85, Day 87, Day 91, Day 113, Day 162, Day 339, Day 344, Week 12 and Week 24 ]
    SF-36v2 acute health survey questionnaire was developed as part of the Rand Health Insurance Experiment and consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for participants (Par) who received at least one dose of 100 mg OL Sirukumab has been presented. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  71. Part B: Change From Baseline in 36-item SF-36 v2 Acute Score Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Day 23, Day 29, Day 30, Day 57, Day 59, Day 64, Day 65 , Day 85, Day 112, Day 113, Day 163, Day 169, Day 373, Week 8 and Week 12 ]
    SF-36v2 acute health survey questionnaire was developed as part of the Rand Health Insurance Experiment and consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for participants (Par) who never received 100 mg OL Sirukumab has been presented. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  72. Part B: Change From Baseline in EQ-5D-5L Index Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Day 85, Day 87, Day 91, Day 113, Day 162, Day 339, Day 344, Week 12 and Week24 ]
    EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). Baseline was last measurement done up to and including Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  73. Part B: Change From Baseline in EQ-5D-5L Index Score Over Time for Participants Who Never Received 100mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Day 29, 30, 57, 59, 64, 65, 85, 112, 113,163,169 and 373, Week 12 ]
    EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). Baseline was last measurement done up to and including Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  74. Part B: Change From Baseline in FACIT-Fatigue Scores Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Day 85,87,91,113,162, 344,339,Week 12, 24 ]
    The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  75. Part B: Change From Baseline in FACIT-Fatigue Scores Over Time for Participants Who Never Received 100mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24 ]
    The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported.

  76. Part B: Change From Baseline in Pain NRS Scores Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24 ]
    The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain now on an 11-point numeric rating scale ranging from 0, "no pain" to 10, "the worst pain imaginable". Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  77. Part B: Change From Baseline in Pain NRS Scores Over Time for Participants Who Never Received at Least One Dose of 100mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24 ]
    The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain now on an 11-point numeric rating scale ranging from 0, "no pain" to 10, "the worst pain imaginable". Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported.

  78. Part B: HAQDI Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Day 87, 339, 344, Week 12, 24 ]
    Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing "no difficulty" (0), "some difficulty" (1), "much difficulty" (2), and "unable to do" (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability

  79. Part B: HAQDI Score Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B [ Time Frame: Day 29, 64, 65, 85, 112, 113, 169, 373 and Week 12 ]
    Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing "no difficulty" (0), "some difficulty" (1), "much difficulty" (2), and "unable to do" (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability

  80. Part B: Change From Baseline in PtGA Score for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38, 40; Days 85, 87, 91, , 113, 162, 339, and 344 ]
    The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS). of 10 centimeter (cm) ranging from 0 ("very well) to 10 ("very poor"). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  81. Part B: Change From Baseline in PtGA Score for Participants Who Never Received 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0), Weeks 2, 4, 8, 12, 16, 36; Days 23, 29, 30, 57, 59, 64, 65, 85,112, 113, 115, 163, 169 and 373 ]
    The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS). of 10 centimeter (cm) ranging from 0 ("very well) to 10 ("very poor"). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported.

  82. Part B: Change From Baseline in PhGA Score for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Day 85, Day 113, Day 162, Day 203, Day 339, Day 344, Week 2, Week 4, Week 8, Week 12, Week 14, Week 16, Week 24, Week 36, Week 38, Week 40 ]
    In PhGA was based on "What is physician's assessment of the participant's current disease activity". PhGA used a 10 cm VAS ranging from 0 ("none") to 10 ("extremely active"). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  83. Part B: Change From Baseline in PhGA Score for Participants Who Never Received 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0), Weeks 4, 8, 12, 16, 36; Days 23, 29, 30, 57, 59, 64, 65, 85, 112, 113, 163, 169 and 373 ]
    In PhGA was based on "What is physician's assessment of the participant's current disease activity". PhGA used a 10 cm VAS ranging from 0 ("none") to 10 ("extremely active"). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported.

  84. Part B: Number of Participants With PGIC Score Over Time Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 1), Days 103 and 271 ]
    Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category.

  85. Part B: Number of Participants With PGIC Score Over Time Who Never Received 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 1) ]
    Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category.

  86. Part B: Change From Baseline in CRP Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected for analysis of CRP. Data for Change from Baseline in serum CRP over time for part B was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  87. Part B: Change From Baseline in CRP Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0), Weeks 4, 8, 12, 16, 24 and 36 ]
    Blood samples were collected for analysis of CRP. Data for Change from Baseline in serum CRP over time for part B was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  88. Part B: Change From Baseline in ESR Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 ]
    Blood samples were collected for analysis of ESR. Data for Change from Baseline in ESR over time for part A was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  89. Part B: Change From Baseline in ESR Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0), Weeks 4, 8, 12, 16, 24 and 36 ]
    Blood samples were collected for analysis of ESR. Data for Change from Baseline in ESR over time for part A was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  90. Part B: Change From Baseline in EQ-5D-5L VAS Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Days 85, 87, 91, 113, 162, 339 and 344 and Weeks 12 and 24 ]
    EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 6 dimensions: 1.Mobility, 2.Self, 3.Usual Activities, 4.Pain/Discomfort, 5.Anxiety/Depression; 6.How good or or bad your health is today. Each of these 6 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 'Best imaginable health state' and 'Worst imaginable health state'. Answers to 'How good or bad your health is today' were measured on a 100 point VAS scale. Baseline for Part B is the last non-missing measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

  91. Part B: Change From Baseline in EQ-5D-5L VAS Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B [ Time Frame: Baseline (Day 0) and Days 23, 29, 30, 57, 59, 64, 65, 85, 112, 113, 163, 169, 344 and 373 and Week 12 ]
    EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 6 dimensions: 1.Mobility, 2.Self, 3.Usual Activities, 4.Pain/Discomfort, 5.Anxiety/Depression; 6.How good or or bad your health is today. Each of these 6 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 100 (Best imaginable health state) and 0 (Worst imaginable health state). Answers to 'How good or bad your health is today' were measured on a 100 point VAS scale. Baseline for Part B is the last non-missing measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of GCA defined by the following Revised GCA Diagnosis Criteria:

Age >=50 years. History of ESR >=50 millimeter/hour (mm/hour) or CRP >=2.45 milligram/deciliter(mg/dL).

Presence of at least one of the following: Unequivocal cranial symptoms of GCA; Unequivocal symptoms of polymyalgia rheumatic (PMR).

Presence of at least one of the following: Temporal artery biopsy revealing features of GCA; Evidence of large-vessel vasculitis by angiography or cross-sectional imaging.

  • Active GCA within 6 weeks of Randomization (Baseline) where active disease is defined by an ESR >=30 mm/hr or CRP >=1 mg/dL AND the presence of at least one of the following:

Unequivocal cranial symptoms of GCA; Unequivocal symptoms of PMR; Other features judged by the clinician investigator to be consistent with GCA or PMR flares.

  • At screening, receiving or able to receive prednisone 20-60 mg/day for the treatment of active GCA.
  • Clinically stable GCA disease at baseline such that the subject is able to safely participate in the blinded prednisone taper regimen in the opinion of the investigator.
  • Practicing acceptable methods of birth control if a female of child-bearing potential.
  • No evidence of active or latent infection with Mycobacterium tuberculosis (TB).

Exclusion Criteria:

  • Are pregnant or breastfeeding.
  • Recent (within the past 12 weeks) or planned major surgery that would impact on study procedures or assessments.
  • Organ transplantation recipients (except corneas within 3 months prior to baseline visit).
  • Had prior treatment with any of the following:

Systemic immunosuppressives) within 4 weeks of baseline; Biologic agents targeted at reducing tumor necrosis factor-alpha (TNF-alpha) within 2-8 weeks of baseline, depending on the agent; Any prior use of tocilizumab or other anti-IL-6 agents; B-cell depleting agents (eg, rituximab) within 12 months prior to baseline or longer if B cell counts have not returned to normal range or baseline levels; Cytotoxic drugs such as cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating agents within 4 weeks of baseline; Abatacept within 8 weeks of baseline; Tofacitinib within 4 weeks of baseline; Methotrexate use within 2 weeks of baseline.

Methylprednisolone > 100 mg/day intravenous (IV) (or equivalent) within 8 weeks of baseline.

  • History of severe allergic reactions to monoclonal antibodies, human proteins, or excipients.
  • Evidence of serious concomitant disease, which in the opinion of the investigator makes them unsuitable for participation in the study.
  • Major ischemic event, unrelated to GCA, within 12 weeks of screening.
  • Marked baseline prolongation of corrected QT (QTc) interval >= 450 milliseconds (msec) (QTc by Bazett's formula [QTcB ]or QTc by Fridericia's formula [QTcF] ), history of Torsade de Pointes, family history of long QT syndrome, history of second or third degree heart block.
  • Current liver disease that could interfere with the trial
  • History of or current active diverticulitis, inflammatory bowel disease, or other symptomatic gastrointestinal tract condition that might predispose to bowel perforation.
  • History of known demyelinating diseases such as multiple sclerosis or optic neuritis.
  • Active infections, or history of recurrent infections or have required management of acute or chronic infections, as follows:

Currently on any suppressive therapy for a chronic infection, history or suspicion of chronic infection, hospitalization for treatment of infection within 60 days of the baseline visit, or use of parenteral (IV) or intra-muscular [IM]) antimicrobials within 60 days of baseline or oral antimicrobials within 30 days of baseline

  • Primary or secondary immunodeficiency or any other autoimmune disease.
  • Human immunodeficiency virus (HIV) infection, hepatitis C or hepatitis B infection
  • Live virus or bacterial vaccination within 3 months before the first administration of study drug

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02531633


Locations
Show Show 63 study locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] November 17, 2016
Statistical Analysis Plan  [PDF] June 4, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02531633    
Other Study ID Numbers: 201677
First Posted: August 24, 2015    Key Record Dates
Results First Posted: May 31, 2019
Last Update Posted: July 31, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Keywords provided by GlaxoSmithKline:
Giant Cell Arteritis, Sirukumab, Prednisone
Additional relevant MeSH terms:
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Polymyalgia Rheumatica
Giant Cell Arteritis
Arteritis
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Skin Diseases, Vascular
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Prednisone
Antibodies, Monoclonal
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors