ANZCTR - Registration

Registration number

NCT02531633

Ethics application status

Date submitted

6/07/2015

Date registered

24/08/2015

Date last updated

31/07/2019

Titles & IDs

Public title

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

Scientific 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

Secondary ID [1]

201677

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Giant Cell Arteritis

Condition category

Condition code

Musculoskeletal

Other muscular and skeletal disorders

Inflammatory and Immune System

Other inflammatory or immune system disorders

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Neurological

Other neurological disorders

Inflammatory and Immune System

Autoimmune diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Sirukumab
Treatment: Drugs - Placebo to match sirukumab
Treatment: Drugs - Prednisone
Treatment: Drugs - Placebo to match prednisone

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.

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.

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.

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.

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.

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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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).

Treatment: Drugs: Placebo to match prednisone
Placebo to match prednisone will be provided as tablets.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part A: Number of Participants in Sustained Remission at Week 52

Timepoint [1]

Week 52

Secondary outcome [1]

Part B: Number of Participants Who Remained in Sustained Remission Without Requirement for Rescue Therapy or Treatment Change at Week 24

Timepoint [1]

Week 24

Secondary outcome [2]

Part A: Cumulative Prednisone Dose Over Time

Timepoint [2]

Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Secondary outcome [3]

Part B: Number of Participants in Sustained Remission Over Time

Timepoint [3]

Weeks 4, 8 and 12

Secondary outcome [4]

Part A: Time to First Disease Flare After Clinical Remission

Timepoint [4]

Week 52

Secondary outcome [5]

Part B: Time to First Disease Flare for Participants in Sustained Remission

Timepoint [5]

Week 52

Secondary outcome [6]

Part A: Number of Disease Flares Over Time

Timepoint [6]

Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Secondary outcome [7]

Part A: Number of Participants With at Least One Hospitalization for Disease Flare

Timepoint [7]

Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Secondary outcome [8]

Part A: Number of Hospitalizations for Disease Flare Over Time

Timepoint [8]

Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Secondary outcome [9]

Part A: Mean 36-item Short Form Health Survey Version 2 (SF-36 v2) Acute Score Over Time

Timepoint [9]

Baseline (Week 0), Weeks 12, 24, 36, 52

Secondary outcome [10]

Part A: Mean EuroQol - 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score Over Time

Timepoint [10]

Baseline (Week 0) and Weeks 12, 24, 36, 52

Secondary outcome [11]

Part A: Mean EQ-5D-5L Visual Analogue Scale (VAS) Over Time

Timepoint [11]

Baseline (Week 0) and Weeks 12, 24, 36, 52

Secondary outcome [12]

Part A: Mean Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-Fatigue) Scores Over Time

Timepoint [12]

Baseline (Week 0), Weeks 12, 24, 36, 52

Secondary outcome [13]

Part A: Mean Pain Numeric Rating Scale (NRS) Scores Over Time

Timepoint [13]

Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Secondary outcome [14]

Part A: Mean Health Assessment Questionnaire - Disability Index (HAQDI) Score Over Time

Timepoint [14]

Baseline (Week 0) and Weeks 12, 24, 36 and 52

Secondary outcome [15]

Part A: Number of Participants With Patient Global Impression of Change (PGIC) Score Over Time

Timepoint [15]

Weeks 12, 24 and 52

Secondary outcome [16]

Part A: Mean Patient Global Assessment of Disease Activity (PtGA) Score Over Time

Timepoint [16]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Secondary outcome [17]

Part A: Mean Physician Global Assessment of Disease Activity (PhGA) Score Over Time

Timepoint [17]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Secondary outcome [18]

Part A: Change From Baseline in Serum C Reactive Protein (CRP) Over Time

Timepoint [18]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Secondary outcome [19]

Part A: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Over Time

Timepoint [19]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Secondary outcome [20]

Part A: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs) and Corticosteroid Related AEs

Timepoint [20]

Up to 52 weeks

Secondary outcome [21]

Part A: Change From Baseline in : Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Timepoint [21]

Baseline (Week 0), Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [22]

Part A: Change From Baseline in Pulse Rate

Timepoint [22]

Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [23]

Part A: Change From Baseline in Temperature

Timepoint [23]

Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [24]

Part A: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets

Timepoint [24]

Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [25]

Part A: Change From Baseline in Hematology Parameters- Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin

Timepoint [25]

Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [26]

Part A: Change From Baseline in Hematology Parameter-Hematocrit

Timepoint [26]

Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [27]

Part A: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume

Timepoint [27]

Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [28]

Part A:Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin

Timepoint [28]

Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [29]

Part A:Change From Baseline in Hematology Parameter- Erythrocytes

Timepoint [29]

Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [30]

Part A: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea

Timepoint [30]

Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [31]

Part A: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein

Timepoint [31]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [32]

Part A: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)

Timepoint [32]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [33]

Part A: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin

Timepoint [33]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary outcome [34]

Part A: Mean Serum Concentrations of Sirukumab

Timepoint [34]

Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 44 and 52

Secondary outcome [35]

Part A: Mean Serum Anti-sirukumab Antibodies

Timepoint [35]

Baseline (Week 0) and up to 52 weeks

Secondary outcome [36]

Part A: Change From Baseline in Free and Total Interleukin-6 (IL-6) Over Time

Timepoint [36]

Baseline (Week 0) and up to 52 weeks

Secondary outcome [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

Timepoint [37]

Up to 120 weeks

Secondary outcome [38]

Part B: Number of Participants With AEs, SAEs and Corticosteroid Related AEs Who Never Received 100mg OL Sirukumab in Part B

Timepoint [38]

Up to 120 weeks

Secondary outcome [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

Timepoint [39]

Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120)

Secondary outcome [40]

Part B: Change From Baseline in SBP and DBP for Participants Who Never Received 100 mg Open Label Sirukumab in Part B

Timepoint [40]

Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120)

Secondary outcome [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

Timepoint [41]

Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120)

Secondary outcome [42]

Part B: Change From Baseline in Pulse Rate for Participants Who Never Received 100 mg Open Label Sirukumab in Part B

Timepoint [42]

Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120)

Secondary outcome [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

Timepoint [43]

Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120)

Secondary outcome [44]

Part B: Change From Baseline in Temperature for Participants Who Never Received 100 mg Open Label Sirukumab in Part B

Timepoint [44]

Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120)

Secondary outcome [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

Timepoint [45]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [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

Timepoint [46]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [47]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [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

Timepoint [48]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [49]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [50]

Part B: Change From Baseline in Hematology Parameter-Hematocrit for Participants Who Never Received 100 mg Open Label Sirukumab in Part B

Timepoint [50]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [51]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [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

Timepoint [52]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [53]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [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

Timepoint [54]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [55]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [56]

Part B: Change From Baseline in Hematology Parameter- Erythrocytes for Participants Who Never Received 100 mg Open Label Sirukumab in Part B

Timepoint [56]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [57]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [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

Timepoint [58]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [59]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [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

Timepoint [60]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [61]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [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

Timepoint [62]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [63]

Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [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

Timepoint [64]

Baseline (Week 0) and Weeks 4,8,12,16,24 and 36

Secondary outcome [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

Timepoint [65]

Weeks 2, 4, 8, 12, 14, 16, 24, 28, 32 and 38

Secondary outcome [66]

Part B: Cumulative Prednisone Dose Over Time for Participants Who Never Received 100 mg Open Label Sirukumab in Part B

Timepoint [66]

Weeks 2, 4, 8, 12, 14, 16, 24, 28, 32 and 38

Secondary outcome [67]

Part B: Number of Disease Flares Over Time

Timepoint [67]

Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [68]

Part B: Number of Participants Requiring at Least One Hospitalization for Disease Flare

Timepoint [68]

Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [69]

Part B: Number of Hospitalizations for Disease Flare Over Time

Timepoint [69]

Up to Week 104

Secondary outcome [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

Timepoint [70]

Baseline (Day 0), Day 85, Day 87, Day 91, Day 113, Day 162, Day 339, Day 344, Week 12 and Week 24

Secondary outcome [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

Timepoint [71]

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

Secondary outcome [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

Timepoint [72]

Baseline (Day 0) and Day 85, Day 87, Day 91, Day 113, Day 162, Day 339, Day 344, Week 12 and Week24

Secondary outcome [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

Timepoint [73]

Baseline (Day 0) and Day 29, 30, 57, 59, 64, 65, 85, 112, 113,163,169 and 373, Week 12

Secondary outcome [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

Timepoint [74]

Baseline (Day 0) and Day 85,87,91,113,162, 344,339,Week 12, 24

Secondary outcome [75]

Part B: Change From Baseline in FACIT-Fatigue Scores Over Time for Participants Who Never Received 100mg OL Sirukumab in Part B

Timepoint [75]

Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24

Secondary outcome [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

Timepoint [76]

Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24

Secondary outcome [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

Timepoint [77]

Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24

Secondary outcome [78]

Part B: HAQDI Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B

Timepoint [78]

Day 87, 339, 344, Week 12, 24

Secondary outcome [79]

Part B: HAQDI Score Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B

Timepoint [79]

Day 29, 64, 65, 85, 112, 113, 169, 373 and Week 12

Secondary outcome [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

Timepoint [80]

Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38, 40; Days 85, 87, 91, , 113, 162, 339, and 344

Secondary outcome [81]

Part B: Change From Baseline in PtGA Score for Participants Who Never Received 100 mg OL Sirukumab in Part B

Timepoint [81]

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

Secondary outcome [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

Timepoint [82]

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

Secondary outcome [83]

Part B: Change From Baseline in PhGA Score for Participants Who Never Received 100 mg OL Sirukumab in Part B

Timepoint [83]

Baseline (Day 0), Weeks 4, 8, 12, 16, 36; Days 23, 29, 30, 57, 59, 64, 65, 85, 112, 113, 163, 169 and 373

Secondary outcome [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

Timepoint [84]

Baseline (Day 1), Days 103 and 271

Secondary outcome [85]

Part B: Number of Participants With PGIC Score Over Time Who Never Received 100 mg OL Sirukumab in Part B

Timepoint [85]

Baseline (Day 1)

Secondary outcome [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

Timepoint [86]

Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [87]

Part B: Change From Baseline in CRP Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B

Timepoint [87]

Baseline (Day 0), Weeks 4, 8, 12, 16, 24 and 36

Secondary outcome [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

Timepoint [88]

Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40

Secondary outcome [89]

Part B: Change From Baseline in ESR Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B

Timepoint [89]

Baseline (Day 0), Weeks 4, 8, 12, 16, 24 and 36

Secondary outcome [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

Timepoint [90]

Baseline (Day 0) and Days 85, 87, 91, 113, 162, 339 and 344 and Weeks 12 and 24

Secondary outcome [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

Timepoint [91]

Baseline (Day 0) and Days 23, 29, 30, 57, 59, 64, 65, 85, 112, 113, 163, 169, 344 and 373 and Week 12

Eligibility

Key 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).

Minimum age

50 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key 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

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Stopped early

Date of first participant enrolment

Anticipated

Actual

16/10/2015

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

21/03/2018

Sample size

Target

Accrual to date

Final

161

Recruitment in Australia

Recruitment state(s)

NSW,SA,VIC,WA

Recruitment hospital [1]

GSK Investigational Site - Camperdown

Recruitment hospital [2]

GSK Investigational Site - Kogarah

Recruitment hospital [3]

GSK Investigational Site - Woodville

Recruitment hospital [4]

GSK Investigational Site - Heidelberg

Recruitment hospital [5]

GSK Investigational Site - Malvern East

Recruitment hospital [6]

GSK Investigational Site - Victoria Park

Recruitment postcode(s) [1]

2050 - Camperdown

Recruitment postcode(s) [2]

2217 - Kogarah

Recruitment postcode(s) [3]

5011 - Woodville

Recruitment postcode(s) [4]

3084 - Heidelberg

Recruitment postcode(s) [5]

3145 - Malvern East

Recruitment postcode(s) [6]

6100 - Victoria Park

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Colorado

Country [2]

United States of America

State/province [2]

Florida

Country [3]

United States of America

State/province [3]

Iowa

Country [4]

United States of America

State/province [4]

Massachusetts

Country [5]

United States of America

State/province [5]

Minnesota

Country [6]

United States of America

State/province [6]

New York

Country [7]

United States of America

State/province [7]

Pennsylvania

Country [8]

United States of America

State/province [8]

Tennessee

Country [9]

United States of America

State/province [9]

Texas

Country [10]

United States of America

State/province [10]

Washington

Country [11]

Belgium

State/province [11]

Leuven

Country [12]

Belgium

State/province [12]

Liège

Country [13]

Bulgaria

State/province [13]

Plovdiv

Country [14]

Bulgaria

State/province [14]

Sofia

Country [15]

France

State/province [15]

Bobigny

Country [16]

France

State/province [16]

Orleans

Country [17]

France

State/province [17]

Paris

Country [18]

Germany

State/province [18]

Baden-Wuerttemberg

Country [19]

Germany

State/province [19]

Niedersachsen

Country [20]

Germany

State/province [20]

Nordrhein-Westfalen

Country [21]

Germany

State/province [21]

Sachsen

Country [22]

Germany

State/province [22]

Thueringen

Country [23]

Germany

State/province [23]

Bad Abbach

Country [24]

Germany

State/province [24]

Berlin

Country [25]

Germany

State/province [25]

Hamburg

Country [26]

Germany

State/province [26]

Kirchheim unter Teck

Country [27]

Germany

State/province [27]

München

Country [28]

Hungary

State/province [28]

Budapest

Country [29]

Hungary

State/province [29]

Debrecen

Country [30]

Italy

State/province [30]

Emilia-Romagna

Country [31]

Italy

State/province [31]

Lombardia

Country [32]

Italy

State/province [32]

Rozzano

Country [33]

Netherlands

State/province [33]

Almelo

Country [34]

Netherlands

State/province [34]

Groningen

Country [35]

Netherlands

State/province [35]

Nijmegen

Country [36]

New Zealand

State/province [36]

Hamilton

Country [37]

New Zealand

State/province [37]

Timaru

Country [38]

Poland

State/province [38]

Krakow

Country [39]

Spain

State/province [39]

Barcelona

Country [40]

Spain

State/province [40]

Bilbao

Country [41]

Spain

State/province [41]

La Coruña

Country [42]

Spain

State/province [42]

La Laguna

Country [43]

United Kingdom

State/province [43]

Essex

Country [44]

United Kingdom

State/province [44]

Merseyside

Country [45]

United Kingdom

State/province [45]

Suffolk

Country [46]

United Kingdom

State/province [46]

Yorkshire

Country [47]

United Kingdom

State/province [47]

Edinburgh

Country [48]

United Kingdom

State/province [48]

Leeds

Country [49]

United Kingdom

State/province [49]

Oxford

Country [50]

United Kingdom

State/province [50]

Reading

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

GlaxoSmithKline

Country

Ethics approval

Ethics application status

Summary

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.

Trial website

https://clinicaltrials.gov/study/NCT02531633

Public notes

Contacts

Principal investigator

Name

GSK Clinical Trials

Address

GlaxoSmithKline

Country

Phone

Email

Contact person for public queries

Name

Address

Country

Phone

Email

Contact person for scientific queries

Trial Review

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For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02531633