Sclerosis, Systemic
Conditions
Brief summary
This multicenter, randomized, double-blind, placebo-controlled, two-arm, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in participants with systemic sclerosis. Participants will be randomized to receive either RoActemra/Actemra 162 mg subcutaneously weekly or placebo for 48 weeks. From Week 48 to Week 96, all participants will receive open-label RoActemra/Actemra 162 mg subcutaneously weekly. Anticipated time on study treatment is 96 weeks.
Interventions
DRUGPlacebo
Subcutaneously weekly, Weeks 0-48
DRUGtocilizumab [RoActemra/Actemra]
162 mg subcutaneously weekly, Weeks 0-48
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 years of age * Systemic sclerosis, as defined by American College of Rheumatology (1980) criteria * Disease duration of \</= 60 months (defined as time from first non-Raynaud phenomenon manifestation) * \>/= 15 and \</= 40 mRSS units at screening * Active disease, as defined by protocol * Uninvolved skin at injection sites * Negative pregnancy test for a female subject of childbearing potential
Exclusion criteria
* Major surgery (including joint surgery) within 8 weeks prior to and/or during study enrollment * Rheumatic autoimmune disease other than systemic sclerosis * Skin thickening (scleroderma) limited to areas distal to the elbows or knees at screening * Previous treatment with tocilizumab * History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies * Severe cardiopulmonary disease * Known active current or history of recurrent infections * Use of any investigational, biologic, or immunosuppressive therapies including intra-articular or parenteral corticosteroids prior to study enrollment as specified in the protocol * As specified in the protocol, any current or past medical condition or medical history involving but not limited to the nervous, renal, pulmonary, endocrine, and gastrointestinal organ systems determined by the Principal Investigator to pose a significant safety risk to any subject while participating in the study * Primary or secondary immunodeficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24 | Baseline, Week 24 | Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement. |
| Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Week 48 | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 8 after last dose that were absent before treatment or that worsened relative to pretreatment state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48 | Baseline, Weeks 24 and 48 | The Clinician's Global Assessment evaluated the overall impact of SSc on the participant as assessed by the physician on a VAS with scores ranging from 0 to 100 mm, with higher scores indicating worse disease in terms of severity, damage, or overall disease, but there was no standardization for the scale. |
| Change From Baseline in Patient's Global Assessment at Week 24 and Week 48 | Baseline, Weeks 24 and 48 | The Patient's Global Assessment was a patient's reported outcome that represented the participant's overall assessment of his or her current SSc on a 100 mm horizontal VAS scale (0 mm to 100 mm), with higher scores indicating worsening disease. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48 | Baseline, Weeks 24 and 48 | This FACIT-Fatigue Scale was a 13-item measure with participants scoring each item on a 5-point scale (0 to 4) up to 52 points. The endpoint measured was fatigue. On this scale, a numerical increase indicated an improvement in the participant's condition. |
| Change From Baseline in 5-D Itch Scale at Week 24 and Week 48 | Baseline, Weeks 24 and 48 | The 5-D Itch Scale contained five domains of duration, degree, direction, disability, and distribution. The endpoint of the scale was pruritus. Each domain was scored on a 5-point scale, the scores of each of the five domains were achieved separately and then summed together to obtain a total 5-D score. 5-D scores ranged between 5 (no pruritus) and 25 (most severe pruritus). |
| Change From Baseline in mRSS at Week 48 | Baseline, Week 48 | Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement. |
| Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Baseline, Weeks 24 and 48 | SHAQ-DI assessed five scleroderma-specific visual analogue scale (VAS) items to explore the impact of participant's disease. These items were developed to measure the effect of scleroderma on five elements of disease that could have a great impact on a participant's daily activities. Each VAS item was rated separately (0-100 millimeters \[mm\]), with higher scores indicating more severe disease. The five items were: 1) intestinal disease, 2) breathing problem, 3) Raynaud syndrome, 4) finger ulcers, and 5) overall disease. |
| Change From Baseline in Tender Joint Count 28 (TJC28) | Baseline, Weeks 3, 8, 16, 24, 32, 40, and 48 | Joint tenderness was evaluated as per assessment of 28 joints. Joints on both sides of the body, including shoulders, elbows, wrists, 10 metacarpal phalangeal (MCP) joints, 10 proximal interphalangeal joint (PIP) joints, and both knees, were assessed. Joints were classified as not tender = 0 or tender = 1. Observed data was presented for this outcome measure. |
| Area Under the Concentration-Time Curve (AUC) From Time 0 to 168 Hour (AUC0-168) | Pre-dose, 24, 48, 72, 96, 120 or 144, and 168 hours post dose for Baseline and Week 16 | AUC was a measure of the serum concentration of the drug over time which was measured in micrograms times (\*) hour per milliliters (µg\*hr/mL). It is used to characterize drug absorption. |
| Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48 | Observed data was presented for this outcome measure. |
| Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48 | Observed data was presented for this outcome measure. |
| Percentage of Participants With Anti-Tocilizumab Antibody | Baseline, and post-baseline (up to Week 48) | — |
| Percentage of Participants Who Maintained or Improved in mRSS From Week 24 to Week 48 | Week 48 | Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement. Percentage of participants with an improvement in mRSS at Week 24 (change from baseline \<0) that maintained or further improved at Week 48 were reported as Yes and No with Yes = improvers at week 24 that had a change from baseline in mRSS at Week 48 \<= change from baseline at Week 24. |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48 | Baseline, Weeks 24 and 48 | The HAQ-DI scale consisted of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The total score indicated the participant's self-assessed level of disability. There are four possible responses for each component: 0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; 3 = unable to do. The HAQ-DI was the sum of the domain scores, divided by the number of domains that have a score (i.e. the average score), with total range of 0 to 3, higher scores showing larger functional limitation. |
Countries
Canada, France, Germany, United Kingdom, United States
Participant flow
Pre-assignment details
Randomization was stratified by joint involvement at baseline (\>=4 or \<4 tender joints of 28 tender joint count \[TJC\]). The study consisted of double-blind (Week 0-Week 48) and open-label (Week 48-Week 96) periods. Data analyzed up to Weeks 24 and 48 (data cut-off: 11 July 2014), and up to Week 96 (data cut-off: 05 August 2015) are reported.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received TCZ matched placebo by SC injection qw for Week 0 to Week 48 (blinded-treatment period) and then received TCZ (162 mg) SC injection qw in the open-label period for Week 48 to Week 96. | 44 |
| Tocilizumab Participants received TCZ (162 mg) by SC injection qw for Week 0 to Week 48 (blinded-treatment period) and then in the open-label period for Week 48 to Week 96. | 43 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded-Treatment Period (Up to Week 24) | Adverse Event | 2 | 3 |
| Blinded-Treatment Period (Up to Week 24) | Death | 0 | 1 |
| Blinded-Treatment Period (Up to Week 24) | Lack of Efficacy | 1 | 1 |
| Blinded-Treatment Period (Up to Week 24) | Lost to Follow-up | 0 | 1 |
| Blinded-Treatment Period (Up to Week 24) | Non-compliance | 1 | 0 |
| Blinded-Treatment Period (Up to Week 24) | Withdrawal by Subject | 4 | 2 |
| Blinded-Treatment Period (Up to Week 48) | Adverse Event | 4 | 5 |
| Blinded-Treatment Period (Up to Week 48) | Death | 0 | 3 |
| Blinded-Treatment Period (Up to Week 48) | Lack of Efficacy | 0 | 1 |
| Blinded-Treatment Period (Up to Week 48) | Lost to Follow-up | 0 | 1 |
| Blinded-Treatment Period (Up to Week 48) | Non-Compliance | 1 | 0 |
| Blinded-Treatment Period (Up to Week 48) | Physician Decision | 1 | 0 |
| Blinded-Treatment Period (Up to Week 48) | Withdrawal by Subject | 5 | 3 |
| Open-label Period (Week 48 to Week 96) | Adverse Event | 4 | 1 |
| Open-label Period (Week 48 to Week 96) | Lack of Efficacy | 1 | 1 |
| Open-label Period (Week 48 to Week 96) | Non-compliance | 1 | 0 |
| Open-label Period (Week 48 to Week 96) | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Tocilizumab | Total |
|---|---|---|---|
| Age, Continuous | 48.1 years STANDARD_DEVIATION 12.9 | 51.2 years STANDARD_DEVIATION 11.7 | 49.6 years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 35 Participants | 32 Participants | 67 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 44 | 28 / 43 | 32 / 44 | 34 / 43 | 39 / 44 | 38 / 43 |
| serious Total, serious adverse events | 11 / 44 | 9 / 43 | 15 / 44 | 14 / 43 | 22 / 44 | 17 / 43 |
Outcome results
Primary
Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24
Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement.
Time frame: Baseline, Week 24
Population: Intent-to-treat (ITT) population included all participants randomized who had received any study drug at the time of the Week 24 cutoff date (14 January 2014). Here, number of participants analyzed included only those participants who were evaluable for this outcome measure at any time point up to Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24 | -1.22 unit on a scale |
| Tocilizumab | Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24 | -3.92 unit on a scale |
Comparison: The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.091595% CI: [-5.85, 0.45]Mixed Models Analysis
Primary
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 8 after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Week 48
Population: Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-emergent adverse events | 90.9 percentage of participants |
| Placebo | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-emergent serious adverse events | 34.1 percentage of participants |
| Tocilizumab | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-emergent adverse events | 97.7 percentage of participants |
| Tocilizumab | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-emergent serious adverse events | 32.6 percentage of participants |
Secondary
Area Under the Concentration-Time Curve (AUC) From Time 0 to 168 Hour (AUC0-168)
AUC was a measure of the serum concentration of the drug over time which was measured in micrograms times (\*) hour per milliliters (µg\*hr/mL). It is used to characterize drug absorption.
Time frame: Pre-dose, 24, 48, 72, 96, 120 or 144, and 168 hours post dose for Baseline and Week 16
Population: Pharmacokinetic (PK) population included all participants who received at least one TCZ injection and had at least one PK sample with detectable results. Here, n = participants evaluable for the specific item at specified time point in specified time frame.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration-Time Curve (AUC) From Time 0 to 168 Hour (AUC0-168) | Baseline (n=7) | 686 µg*hr/mL | Standard Deviation 455 |
| Placebo | Area Under the Concentration-Time Curve (AUC) From Time 0 to 168 Hour (AUC0-168) | Week 16 (n=4) | 7508 µg*hr/mL | Standard Deviation 2369 |
Secondary
Change From Baseline in 5-D Itch Scale at Week 24 and Week 48
The 5-D Itch Scale contained five domains of duration, degree, direction, disability, and distribution. The endpoint of the scale was pruritus. Each domain was scored on a 5-point scale, the scores of each of the five domains were achieved separately and then summed together to obtain a total 5-D score. 5-D scores ranged between 5 (no pruritus) and 25 (most severe pruritus).
Time frame: Baseline, Weeks 24 and 48
Population: ITT population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure and n included those who were evaluable for the specific item at specified time point in specified time frame.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in 5-D Itch Scale at Week 24 and Week 48 | Week 24 (n=41, 41) | -1.73 units on a scale |
| Placebo | Change From Baseline in 5-D Itch Scale at Week 24 and Week 48 | Week 48 (n=40, 41) | -1.08 units on a scale |
| Tocilizumab | Change From Baseline in 5-D Itch Scale at Week 24 and Week 48 | Week 24 (n=41, 41) | -0.94 units on a scale |
| Tocilizumab | Change From Baseline in 5-D Itch Scale at Week 24 and Week 48 | Week 48 (n=40, 41) | -2.19 units on a scale |
Comparison: Change From Baseline in 5-D Itch Scale at Week 24. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.365195% CI: [-0.94, 2.51]Mixed Models Analysis
Comparison: Change From Baseline in 5-D Itch Scale at Week 48. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.284195% CI: [-3.16, 0.94]Mixed Models Analysis
Secondary
Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48
The Clinician's Global Assessment evaluated the overall impact of SSc on the participant as assessed by the physician on a VAS with scores ranging from 0 to 100 mm, with higher scores indicating worse disease in terms of severity, damage, or overall disease, but there was no standardization for the scale.
Time frame: Baseline, Weeks 24 and 48
Population: ITT population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure and n included those who were evaluable for the specific item at specified time point in specified time frame.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48 | Week 24 (n=41, 39) | -7.25 mm |
| Placebo | Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48 | Week 48 (n=41, 40) | -9.39 mm |
| Tocilizumab | Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48 | Week 24 (n=41, 39) | -8.24 mm |
| Tocilizumab | Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48 | Week 48 (n=41, 40) | -18.41 mm |
Comparison: Change From Baseline in Clinician's Global Assessment at Week 24.The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.811895% CI: [-9.2, 7.23]Mixed Models Analysis
Comparison: Change From Baseline in Clinician's Global Assessment at Week 48.The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.076895% CI: [-19.04, 1]Mixed Models Analysis
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48
This FACIT-Fatigue Scale was a 13-item measure with participants scoring each item on a 5-point scale (0 to 4) up to 52 points. The endpoint measured was fatigue. On this scale, a numerical increase indicated an improvement in the participant's condition.
Time frame: Baseline, Weeks 24 and 48
Population: ITT population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure and n included those who were evaluable for the specific item at specified time point in specified time frame.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48 | Week 24 (n=41, 42) | 1.26 units on a scale |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48 | Week 48 (n=40, 42) | 0.36 units on a scale |
| Tocilizumab | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48 | Week 24 (n=41, 42) | 2.68 units on a scale |
| Tocilizumab | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48 | Week 48 (n=40, 42) | 3.11 units on a scale |
Comparison: Change From Baseline in FACIT-Fatigue Score at Week 24. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.519795% CI: [-2.97, 5.82]Mixed Models Analysis
Comparison: Change From Baseline in FACIT-Fatigue Score at Week 48. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.188695% CI: [-1.38, 6.88]Mixed Models Analysis
Secondary
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48
The HAQ-DI scale consisted of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The total score indicated the participant's self-assessed level of disability. There are four possible responses for each component: 0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; 3 = unable to do. The HAQ-DI was the sum of the domain scores, divided by the number of domains that have a score (i.e. the average score), with total range of 0 to 3, higher scores showing larger functional limitation.
Time frame: Baseline, Weeks 24 and 48
Population: ITT population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure and n included those who were evaluable for the specific item at specified time point in specified time frame.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48 | Week 24 (n=42, 41) | 0.118 units on a scale |
| Placebo | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48 | Week 48 (n=41, 41) | 0.205 units on a scale |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48 | Week 24 (n=42, 41) | 0.137 units on a scale |
| Tocilizumab | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48 | Week 48 (n=41, 41) | -0.002 units on a scale |
Comparison: Change From Baseline in HAQ-DI Score at Week 24. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interactionp-value: 0.850395% CI: [-0.186, 0.225]Mixed Models Analysis
Comparison: Change From Baseline in HAQ-DI Score at Week 48. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.121295% CI: [-0.471, 0.056]Mixed Models Analysis
Secondary
Change From Baseline in mRSS at Week 48
Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement.
Time frame: Baseline, Week 48
Population: ITT population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure at specified time point up to 48 weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in mRSS at Week 48 | -2.77 unit on a scale |
| Tocilizumab | Change From Baseline in mRSS at Week 48 | -6.33 unit on a scale |
Comparison: The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.057995% CI: [-7.23, 0.12]Mixed Models Analysis
Secondary
Change From Baseline in Patient's Global Assessment at Week 24 and Week 48
The Patient's Global Assessment was a patient's reported outcome that represented the participant's overall assessment of his or her current SSc on a 100 mm horizontal VAS scale (0 mm to 100 mm), with higher scores indicating worsening disease.
Time frame: Baseline, Weeks 24 and 48
Population: ITT population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure and n included those who were evaluable for the specific item at specified time point in specified time frame.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Patient's Global Assessment at Week 24 and Week 48 | Week 24 (n=42, 42) | 1.53 mm |
| Placebo | Change From Baseline in Patient's Global Assessment at Week 24 and Week 48 | Week 48 (n=41, 42) | -2.70 mm |
| Tocilizumab | Change From Baseline in Patient's Global Assessment at Week 24 and Week 48 | Week 24 (n=42, 42) | -2.33 mm |
| Tocilizumab | Change From Baseline in Patient's Global Assessment at Week 24 and Week 48 | Week 48 (n=41, 42) | -11.00 mm |
Comparison: Change From Baseline in Patient's Global Assessment at Week 24. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.406395% CI: [-13.04, 5.34]Mixed Models Analysis
Comparison: Change From Baseline in Patient's Global Assessment at Week 48. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.137195% CI: [-19.31, 2.71]Mixed Models Analysis
Secondary
Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI)
SHAQ-DI assessed five scleroderma-specific visual analogue scale (VAS) items to explore the impact of participant's disease. These items were developed to measure the effect of scleroderma on five elements of disease that could have a great impact on a participant's daily activities. Each VAS item was rated separately (0-100 millimeters \[mm\]), with higher scores indicating more severe disease. The five items were: 1) intestinal disease, 2) breathing problem, 3) Raynaud syndrome, 4) finger ulcers, and 5) overall disease.
Time frame: Baseline, Weeks 24 and 48
Population: ITT population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure and n included those who were evaluable for the specific item at specified time point in specified timeframe.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Intestinal VAS Score (n=42, 41) | 5.81 mm |
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Breathing VAS Scores (n=42, 41) | 8.54 mm |
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Raynaud syndrome (n=42, 41) | 2.41 mm |
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Finger ulcers VAS Score (n=42, 41) | 9.20 mm |
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Overall disease (n=42, 41) | 1.89 mm |
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Intestinal VAS Score (n=41, 41) | 7.91 mm |
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Breathing VAS Scores (n=41, 41) | 0.55 mm |
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Raynaud syndrome (n=41, 41) | 0.30 mm |
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Finger ulcers VAS Score (n=41, 41) | 4.97 mm |
| Placebo | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Overall disease (n=41, 41) | 3.46 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Raynaud syndrome (n=41, 41) | -4.18 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Intestinal VAS Score (n=42, 41) | 5.38 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Intestinal VAS Score (n=41, 41) | 1.11 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Breathing VAS Scores (n=42, 41) | 4.42 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Overall disease (n=41, 41) | -4.36 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Raynaud syndrome (n=42, 41) | 1.13 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Breathing VAS Scores (n=41, 41) | 2.09 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Finger ulcers VAS Score (n=42, 41) | 14.09 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 48: Finger ulcers VAS Score (n=41, 41) | -0.83 mm |
| Tocilizumab | Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) | Week 24: Overall disease (n=42, 41) | 1.81 mm |
Comparison: Change From Baseline in Intestinal VAS Score at Week 24. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.933695% CI: [-10.78, 9.91]Mixed Models Analysis
Comparison: Change From Baseline in Breathing VAS Score at Week 24. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.460995% CI: [-15.21, 6.96]Mixed Models Analysis
Comparison: Change From Baseline in Raynaud Syndrome Score at Week 24. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.849395% CI: [-14.7, 12.13]Mixed Models Analysis
Comparison: Change From Baseline in Finger Ulcers Score at Week 24. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.471795% CI: [-8.59, 18.37]Mixed Models Analysis
Comparison: Change From Baseline in Overall Disease Score at Week 24. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.987695% CI: [-9.93, 9.78]Mixed Models Analysis
Comparison: Change From Baseline in Intestinal VAS Score at Week 48. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.240795% CI: [-18.3, 4.71]Mixed Models Analysis
Comparison: Change From Baseline in Breathing VAS Score at Week 48. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.774295% CI: [-9.18, 12.26]Mixed Models Analysis
Comparison: Change From Baseline in Raynaud Syndrome Score at Week 48. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.518295% CI: [-18.28, 9.31]Mixed Models Analysis
Comparison: Change From Baseline in Finger Ulcers Score at Week 48. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.310695% CI: [-17.2, 5.59]Mixed Models Analysis
Comparison: Change From Baseline in Overall Disease Score at Week 48. The analysis included the fixed, categorical effects of treatment, visit, the stratification factor of joint involvement at the baseline visit, and treatment-by-visit interaction, as well as the continuous covariates of baseline score and baseline score-by-visit interaction.p-value: 0.171795% CI: [-19.11, 3.48]Mixed Models Analysis
Secondary
Change From Baseline in Tender Joint Count 28 (TJC28)
Joint tenderness was evaluated as per assessment of 28 joints. Joints on both sides of the body, including shoulders, elbows, wrists, 10 metacarpal phalangeal (MCP) joints, 10 proximal interphalangeal joint (PIP) joints, and both knees, were assessed. Joints were classified as not tender = 0 or tender = 1. Observed data was presented for this outcome measure.
Time frame: Baseline, Weeks 3, 8, 16, 24, 32, 40, and 48
Population: ITT population. Here, n = participants evaluable for the specific item at specified time point in specified time frame.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 16 (n=18, 17) | -3.50 joint count | Standard Deviation 6 |
| Placebo | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 32 (n=12, 11) | -3.33 joint count | Standard Deviation 6.62 |
| Placebo | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 8 (n=18, 19) | -3.06 joint count | Standard Deviation 6.67 |
| Placebo | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 40 (n=10, 10) | -3.80 joint count | Standard Deviation 6.76 |
| Placebo | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 24 (n=17, 16) | -2.06 joint count | Standard Deviation 6.28 |
| Placebo | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 48 (n=12, 10) | -2.92 joint count | Standard Deviation 7.08 |
| Placebo | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 3 (n=20, 19) | -2.75 joint count | Standard Deviation 4.27 |
| Tocilizumab | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 48 (n=12, 10) | -5.10 joint count | Standard Deviation 7.29 |
| Tocilizumab | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 3 (n=20, 19) | -2.32 joint count | Standard Deviation 5.55 |
| Tocilizumab | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 8 (n=18, 19) | -4.00 joint count | Standard Deviation 6.16 |
| Tocilizumab | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 16 (n=18, 17) | -3.65 joint count | Standard Deviation 7.59 |
| Tocilizumab | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 24 (n=17, 16) | -4.31 joint count | Standard Deviation 7.34 |
| Tocilizumab | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 32 (n=12, 11) | -3.18 joint count | Standard Deviation 7.4 |
| Tocilizumab | Change From Baseline in Tender Joint Count 28 (TJC28) | Week 40 (n=10, 10) | -4.30 joint count | Standard Deviation 8.23 |
Secondary
Mean Serum Concentrations of Interleukin (IL)-6 by Visit
Observed data was presented for this outcome measure.
Time frame: Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48
Population: Safety population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure and n included those who were evaluable for the specific item at specified time point in specified time frame.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 1: Absolute values (n=43, 43) | 17.24 picograms per milliliters (pg/mL) | Standard Deviation 22.77 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 8: Change From Baseline(n=41,38) | 0.15 picograms per milliliters (pg/mL) | Standard Deviation 18.65 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 2: Change From Baseline (n=42, 40) | -3.07 picograms per milliliters (pg/mL) | Standard Deviation 17.85 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 16: Absolute values (n=32,33) | 12.51 picograms per milliliters (pg/mL) | Standard Deviation 14.06 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Baseline (n=43, 42) | 15.02 picograms per milliliters (pg/mL) | Standard Deviation 18.19 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 16: Change From Baseline (n=31,32) | -1.26 picograms per milliliters (pg/mL) | Standard Deviation 11.34 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 3: Absolute values (n=42, 40) | 12.47 picograms per milliliters (pg/mL) | Standard Deviation 10.72 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 24: Absolute values (n=36,34) | 10.19 picograms per milliliters (pg/mL) | Standard Deviation 10.55 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 1: Change From Baseline (n=42, 42) | 1.33 picograms per milliliters (pg/mL) | Standard Deviation 27.29 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 24: Change From Baseline(n=35,33) | -2.74 picograms per milliliters (pg/mL) | Standard Deviation 12.43 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 3: Change From Baseline (n=41, 39) | -3.60 picograms per milliliters (pg/mL) | Standard Deviation 15.28 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 48: Absolute values (n=32,27) | 10.50 picograms per milliliters (pg/mL) | Standard Deviation 11.82 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 2: Absolute values (n=43, 41) | 12.60 picograms per milliliters (pg/mL) | Standard Deviation 13.78 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 48: Change From Baseline (n=31,26) | -2.61 picograms per milliliters (pg/mL) | Standard Deviation 14.92 |
| Placebo | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 8: Absolute values (n=42, 39) | 15.39 picograms per milliliters (pg/mL) | Standard Deviation 19.04 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 48: Change From Baseline (n=31,26) | 55.60 picograms per milliliters (pg/mL) | Standard Deviation 35.86 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Baseline (n=43, 42) | 13.57 picograms per milliliters (pg/mL) | Standard Deviation 14.69 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 1: Absolute values (n=43, 43) | 158.91 picograms per milliliters (pg/mL) | Standard Deviation 326.42 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 2: Absolute values (n=43, 41) | 107.10 picograms per milliliters (pg/mL) | Standard Deviation 73.75 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 2: Change From Baseline (n=42, 40) | 94.54 picograms per milliliters (pg/mL) | Standard Deviation 67.99 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 3: Absolute values (n=42, 40) | 116.58 picograms per milliliters (pg/mL) | Standard Deviation 75.31 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 3: Change From Baseline (n=41, 39) | 104.44 picograms per milliliters (pg/mL) | Standard Deviation 71.84 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 8: Absolute values (n=42, 39) | 115.31 picograms per milliliters (pg/mL) | Standard Deviation 66.39 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 8: Change From Baseline(n=41,38) | 104.14 picograms per milliliters (pg/mL) | Standard Deviation 62.95 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 16: Absolute values (n=32,33) | 98.36 picograms per milliliters (pg/mL) | Standard Deviation 61.65 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 16: Change From Baseline (n=31,32) | 88.86 picograms per milliliters (pg/mL) | Standard Deviation 59.77 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 24: Absolute values (n=36,34) | 84.67 picograms per milliliters (pg/mL) | Standard Deviation 68.37 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 24: Change From Baseline(n=35,33) | 73.61 picograms per milliliters (pg/mL) | Standard Deviation 68.07 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 48: Absolute values (n=32,27) | 65.30 picograms per milliliters (pg/mL) | Standard Deviation 35.95 |
| Tocilizumab | Mean Serum Concentrations of Interleukin (IL)-6 by Visit | Week 1: Change From Baseline (n=42, 42) | 147.37 picograms per milliliters (pg/mL) | Standard Deviation 326.2 |
Secondary
Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit
Observed data was presented for this outcome measure.
Time frame: Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48
Population: Safety population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure and n included those who were evaluable for the specific item at specified time point in specified time frame.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 2: Change From Baseline (n=43, 40) | 6.13 pg/mL | Standard Deviation 41.6 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 8: Change From Baseline (n=42, 38) | 0.91 pg/mL | Standard Deviation 5.07 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 1: Absolute values (n=44, 43) | 51.03 pg/mL | Standard Deviation 59.12 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 16: Absolute values (n=32, 33) | 37.71 pg/mL | Standard Deviation 10.3 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 3: Absolute values (n=44, 40) | 41.64 pg/mL | Standard Deviation 27.07 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 16: Change From Baseline (n=32, 32) | -0.08 pg/mL | Standard Deviation 5.71 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 2: Absolute values (n=43, 41) | 44.07 pg/mL | Standard Deviation 42.15 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 24: Absolute values (n=36, 34) | 38.72 pg/mL | Standard Deviation 13.06 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 3: Change From Baseline (n=44, 39) | 4.03 pg/mL | Standard Deviation 26 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 24: Change From Baseline (n=36, 33) | 1.11 pg/mL | Standard Deviation 6.47 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 1: Change From Baseline (n=44, 42) | 13.42 pg/mL | Standard Deviation 57.91 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 48: Absolute values (n=32, 27) | 36.52 pg/mL | Standard Deviation 9.93 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 8: Absolute values (n=42, 39) | 38.66 pg/mL | Standard Deviation 11.95 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 48: Change From Baseline (n=32, 26) | -0.75 pg/mL | Standard Deviation 5.2 |
| Placebo | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Baseline (n=44, 42) | 37.61 pg/mL | Standard Deviation 11.12 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 48: Change From Baseline (n=32, 26) | 454.19 pg/mL | Standard Deviation 163.93 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Baseline (n=44, 42) | 39.39 pg/mL | Standard Deviation 10.16 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 1: Absolute values (n=44, 43) | 237.34 pg/mL | Standard Deviation 71.38 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 1: Change From Baseline (n=44, 42) | 198.39 pg/mL | Standard Deviation 69.41 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 2: Absolute values (n=43, 41) | 329.90 pg/mL | Standard Deviation 81.93 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 2: Change From Baseline (n=43, 40) | 291.38 pg/mL | Standard Deviation 79.29 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 3: Absolute values (n=44, 40) | 384.88 pg/mL | Standard Deviation 99.41 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 3: Change From Baseline (n=44, 39) | 346.68 pg/mL | Standard Deviation 95.96 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 8: Absolute values (n=42, 39) | 486.62 pg/mL | Standard Deviation 116.41 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 8: Change From Baseline (n=42, 38) | 447.77 pg/mL | Standard Deviation 114.4 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 16: Absolute values (n=32, 33) | 525.48 pg/mL | Standard Deviation 164.9 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 16: Change From Baseline (n=32, 32) | 486.43 pg/mL | Standard Deviation 163.32 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 24: Absolute values (n=36, 34) | 520.18 pg/mL | Standard Deviation 167.97 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 24: Change From Baseline (n=36, 33) | 482.10 pg/mL | Standard Deviation 168.44 |
| Tocilizumab | Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit | Week 48: Absolute values (n=32, 27) | 491.44 pg/mL | Standard Deviation 164.82 |
Secondary
Percentage of Participants Who Maintained or Improved in mRSS From Week 24 to Week 48
Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement. Percentage of participants with an improvement in mRSS at Week 24 (change from baseline \<0) that maintained or further improved at Week 48 were reported as Yes and No with Yes = improvers at week 24 that had a change from baseline in mRSS at Week 48 \<= change from baseline at Week 24.
Time frame: Week 48
Population: ITT population. Here number of participants analyzed included those with mRSS change from baseline \<0 at Week 24 and with non-missing change from baseline in mRSS at Week 48.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Maintained or Improved in mRSS From Week 24 to Week 48 | 44.4 percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained or Improved in mRSS From Week 24 to Week 48 | 68.2 percentage of participants |
Comparison: The logistic regression model included the fixed categorical effects of treatment and the stratification factor of joint involvement at the baseline visit. The continuous covariate of baseline mRSS score was also included in the model.p-value: 0.215995% CI: [0.6, 9.5]Regression, Logistic
Secondary
Percentage of Participants With Anti-Tocilizumab Antibody
Time frame: Baseline, and post-baseline (up to Week 48)
Population: Safety population. Here, number of participants analyzed included only those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Anti-Tocilizumab Antibody | Baseline | 7.0 percentage of participants |
| Placebo | Percentage of Participants With Anti-Tocilizumab Antibody | Post-Baseline | 0.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Anti-Tocilizumab Antibody | Baseline | 2.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Anti-Tocilizumab Antibody | Post-Baseline | 2.4 percentage of participants |