Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Percentage of Participants Who Achieved Sustained Disease Remission at Week 52 |
Disease remission was defined as resolution of signs and symptoms of giant cell arteries (GCA), and normalization of C-reactive protein (CRP) (<10 mg/L). Sustained remission was defined as meeting all of the following parameters: achievement of disease remission not later than Week 12, absence of disease flare (defined as recurrence of signs and symptoms attributable to active GCA plus an increase in corticosteroid [CS] dose due to GCA or elevation of erythrocyte sedimentation rate [ESR] attributable to active GCA plus an increase in CS dose due to GCA) from Week 12 through Week 52, normalization of CRP (to <10 mg/L, with absence of successive elevations to >=10 mg/L) from Week 12 through Week 52, and successful adherence to prednisone taper from Week 12 through Week 52. |
At Week 52 |
|
| Primary |
Percentage of Participants Who Achieved Sustained Disease Remission at Week 24 |
Disease remission was defined as resolution of signs and symptoms of GCA, and normalization of CRP <10 mg/L. Sustained remission was defined as meeting all of the following parameters: achievement of disease remission not later than Week 12, absence of disease flare (defined as recurrence of signs and symptoms attributable to active GCA plus an increase in CS dose due to GCA, or elevation of ESR attributable to active GCA plus an increase in CS dose due to GCA) from Week 12 through Week 24, normalization of CRP (to <10 mg/L, with an absence of successive elevations to >=10 mg/L) from Week 12 through Week 24, and successful adherence to the prednisone taper from Week 12 through Week 24. |
At Week 24 |
|
| Secondary |
Number of Participants With Achievement of Disease Remission up to Week 12: Week 52 Analysis Set |
Disease remission was defined as resolution of signs and symptoms of GCA, and normalization of CRP (< 10 mg/L). The status of normalization of CRP (<10 mg/L) was determined based on the last two non-missing post-baseline CRP values measured up to Week 12. If at least one of the value was <10 mg/L, then it was considered as normalization of CRP. Participants who took rescue corticosteroid (CS) due to active GCA prior to Week 12 or who permanently withdrew from the study treatment prior to Week 12 were considered as not achieved disease remission by Week 12. |
Up to Week 12 |
|
| Secondary |
Number of Participants With Achievement of Disease Remission up to Week 12: Intent-to-treat (ITT) Population |
Disease remission was defined as resolution of signs and symptoms of GCA, and normalization of CRP (< 10 mg/L). The status of normalization of CRP (<10 mg/L) was determined based on the last two non-missing post-baseline CRP values measured up to Week 12. If at least one of the value was <10 mg/L, then it was considered as normalization of CRP. Participants who took rescue CS due to active GCA prior to Week 12 or who permanently withdrew from the study treatment prior to Week 12 were considered as not achieved disease remission by Week 12. |
Up to Week 12 |
|
| Secondary |
Number of Participants With Absence of Disease Flare From Week 12 Through Week 52: Week 52 Analysis Set |
Disease flare was defined as either recurrence of signs and symptoms attributable to active GCA plus an increase in CS dose due to GCA, or elevation of ESR attributable to active GCA plus an increase in CS dose due to GCA. Number of participants with absence of disease flare from Week 12 through Week 52 were reported. |
From Week 12 through Week 52 |
|
| Secondary |
Number of Participants With Absence of Disease Flare From Week 12 Through Week 24: ITT Population |
Disease flare was defined as either recurrence of signs and symptoms attributable to active GCA plus an increase in CS dose due to GCA, or elevation of ESR attributable to active GCA plus an increase in CS dose due to GCA. Number of participants with absence of disease flare from Week 12 through Week 24 were reported. |
From Week 12 through Week 24 |
|
| Secondary |
Number of Participants With Normalization of C-Reactive Protein From Week 12 Through Week 52: Week 52 Analysis Set |
Normalization of CRP was defined as CRP levels <10 mg/L. If there were two or more consecutive visits with CRP >=10 mg/L, then it was categorized as no normalization of CRP. |
From Week 12 through Week 52 |
|
| Secondary |
Number of Participants With Normalization of C-Reactive Protein (CRP) From Week 12 Through Week 24: ITT Population |
Normalization of CRP was defined as CRP levels <10 mg/L. If there were two or more consecutive visits with CRP >=10 mg/L, then it was categorized as no normalization of CRP. |
From Week 12 through Week 24 |
|
| Secondary |
Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 52: Week 52 Analysis Set |
Successful adherence to the prednisone taper from Week 12 through Week 52 was defined as participants who did not take rescue therapy from Week 12 through Week 52 and might include the use of any excess prednisone (beyond the per protocol CS tapering regimen) with a cumulative dose of <=100 mg (or equivalent), such as those employed to manage adverse event (AE) not related to GCA. |
From Week 12 through Week 52 |
|
| Secondary |
Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 24: ITT Population |
Successful adherence to the prednisone taper from Week 12 through Week 24 was defined as participants who did not take rescue therapy from Week 12 through Week 24 and might include the use of any excess prednisone (beyond the per protocol CS tapering regimen) with a cumulative dose of <=100 mg (or equivalent), such as those employed to manage AE not related to GCA. |
From Week 12 through Week 24 |
|
| Secondary |
Total Cumulative Corticosteroid (Including Prednisone) Dose |
Cumulative dose of CS used for GCA disease was defined as the dose taken up to the end of treatment, including expected prednisone in tapering regimen per protocol, CS used in rescue therapy and the use of commercial prednisone (an excess of <=100 mg of prednisone during the study treatment period employed to manage AE not related to GCA). The total cumulative CS dose was based on the total number of days with complete or partial intake, no imputation was done on missed tablets. |
Up to Week 52 |
|
| Secondary |
Time to First Giant Cell Arteritis Disease Flare |
Time to first GCA flare was defined as the duration (in days) from randomization to first GCA flare after clinical remission (defined as resolution of signs and symptoms and normalization of CRP [<10 mg/L]) and up to 52 weeks. Disease flare was defined as either the recurrence of signs or symptoms attributable to active plus an increase in CS dose due to GCA or elevation of ESR attributable to active GCA plus an increase in CS dose due to GCA. Kaplan-Meier method was used for the analysis. Participants who never achieved remission were censored at randomization day; and those who achieved clinical remission and never flared were censored at the end of treatment assessment date up to Week 52. |
Up to Week 52 |
|
| Secondary |
Composite Glucocorticoid Toxicity Index (C-GTI): Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 24: ITT Population |
GTI assessed glucocorticoid (GC) related morbidity and GC-sparing ability of other therapies; composed of 2 components: Composite GTI and Specific List. Composite GTI contained 9 domains and Specific List contained of 23 items (11 domains), used as complementary tool to C-GTI. Composite GTI score was the sum of 9 domain-specific scores at each visit and Cumulative GTI score was the sum of composite GTI scores across each visit. Two cumulative GTI scores: CWS and AIS at Week 24 are reported in this outcome measure (OM). CWS assessed cumulative GC toxicity regardless of whether toxicity had lasting effects or was transient. AIS assessed new therapy effectiveness in decreasing any Baseline GC toxicity over time. For CWS, composite score ranged from 0 to 439 and for AIS, composite score ranged from -346 to 439. For both CWS and AIS, the minimum score implies the least toxicity and the maximum score implies the most toxicity. |
At Week 24 |
|
| Secondary |
Composite Glucocorticoid Toxicity Index: Cumulative Worsening Score and Aggregate Improvement Score at Week 52 |
GTI assessed glucocorticoid (GC) related morbidity and GC-sparing ability of other therapies; composed of 2 components: Composite GTI and Specific List. Composite GTI contained 9 domains and Specific List contained of 23 items (11 domains), used as complementary tool to C-GTI. Composite GTI score was the sum of 9 domain-specific scores at each visit and Cumulative GTI score was the sum of composite GTI scores across each visit. Two cumulative GTI scores: CWS and AIS at Week 52 are reported in this OM. CWS assessed cumulative GC toxicity regardless of whether toxicity had lasting effects or was transient. AIS assessed new therapy effectiveness in decreasing any Baseline GC toxicity over time. For CWS, composite score ranged from 0 to 439 and for AIS, composite score ranged from -346 to 439. For both CWS and AIS, the minimum score implies the least toxicity and the maximum score implies the most toxicity. |
At Week 52 |
|
| Secondary |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious AEs (SAEs) were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were the AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the investigational medicinal product (IMP) to the last dose of the SC IMP +60 days). |
From first dose (i.e., Day 1) up to 60 days after last dose (i.e., up to Week 60) |
|
| Secondary |
Pharmacokinetics (PK): Serum Trough Concentration (Ctrough) of Sarilumab |
Ctrough was pre dose concentration of drug. Data for this outcome measure was not planned to be collected and analyzed for placebo arms (Placebo+52 Week Taper and Placebo+26 Week Taper) as pre-specified in the protocol. |
Pre-dose on Week 0 (Baseline), Weeks 2, 4, 12, 16, 24 and 52 |
|
| Secondary |
Pharmacokinetics: Serum Drug Concentration of Sarilumab Post-dose at Week 24 |
Serum concentrations of functional sarilumab were analyzed using validated enzyme linked immunosorbent assay. |
post-dose at Week 24 |
|
| Secondary |
Percentage of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response |
ADA response categories: 1) Treatment-boosted ADA positive participant: Participant with a positive ADA assay response at Baseline and with at least a 4-fold increase in titer compared to Baseline during TEAE period. 2) Treatment-emergent ADA positive participant: Participant with non-positive assay (meaning negative or missing) response at Baseline but with a positive assay response during the TEAE period (defined as the time from the first dose of the IMP to the last dose of the SC IMP + 60 days). Titer values were categorized as low (titer <1,000); moderate (1,000<= titer <=10,000) and high (titer >10,000). |
From Day 1 (Baseline) up to last dose date of study drug + 60 days (i.e., up to Week 60) |
|
| Secondary |
Pharmacodynamics: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52 |
ESR is a laboratory test to provide non-specific measure of inflammation in the body. The test assessed the rate at which red blood cells fell in a test tube and was measured in millimeters per hour. |
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52 |
|
| Secondary |
Pharmacodynamics: Change From Baseline in C-reactive Protein (CRP) Level at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52 |
CRP is a protein made by the liver. CRP levels increase in blood when inflammation occurs in the body. |
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52 |
|
| Secondary |
Pharmacodynamics: Change From Baseline in Interleukin-6 (IL-6) at Weeks 2, 12, 24, and 52 |
Interleukin-6 is a protein produced in the body. Levels of IL-6 often increase when there is inflammation (redness, warmth, swelling, and pain as a result of infection, irritation, or injury), either acute or chronic. |
Baseline, Weeks 2, 12, 24, and 52 |
|
| Secondary |
Pharmacodynamics: Change From Baseline in Soluble Interleukin-6 Receptor (sIL-6R) Level at Weeks 2, 12, 24, and 52 |
Interleukin-6 is a protein produced in the body. Levels of IL-6 often increase when there is inflammation (redness, warmth, swelling, and pain as a result of infection, irritation, or injury), either acute or chronic. sIL-6R is one of the receptors that bind IL-6. |
Baseline, Weeks 2, 12, 24, and 52 |
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