Systemic Juvenile Idiopathic Arthritis
Conditions
Keywords
Flare, arthritis, IL-1beta antagonist, systemic juvenile idiopathic arthritis, Juvenile Rheumatoid, Systemic juvenile idiopathic arthritis with active flare
Brief summary
This study assessed the initial efficacy and safety of canakinumab over a 4 week period in patients with systemic juvenile idiopathic arthritis (SJIA) having a flare. Response to treatment will be according to the adapted American College of Rheumatology(ACR)Pediatric 30 criteria at Day 15.
Interventions
DRUGCanakinumab
Canakinumab was supplied in individual 6 mL glass vials each containing 150 mg canakinumab powder as a lyophilized cake. Each reconstituted vial provided 150mg of canakinumab per 1 mL.
DRUGPlacebo
Placebo was provided in individual 6 mL glass vials each containing 150 mg placebo powder matching canakinumab as a lyophilized cake. Each reconstitued vial provided 150mg of placebo per 1 mL.
Sponsors
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Southwest Pediatric Nephrology Study Group
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 19 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of systemic juvenile idiopathic arthritis as per ILAR definition that must have occurred at least 2 months prior to enrollment with onset of disease \< 16 years of age: * Arthritis in one or more joints with or preceded by fever of at least 2 weeks duration that is documented to be daily/quotidian for at least 3 days and accompanied by one or more of the following: * evanescent nonfixed erythematous rash, * generalized lymph node enlargement, * hepatomegaly and/ or splenomegaly, * serositis 2. Parent's or legal guardian's written informed consent and child's assent, if appropriate, or patient's informed consent for ≥ 18 years of age 3. Male and female patients aged ≥ 2 to \< 20 years of age 4. Active disease at the time of enrollment defined as follows: * At least 2 joints with active arthritis * Documented spiking, intermittent fever (body temperature \> 38°C) for at least 1 day during the screening period within 1 week before first canakinumab/placebo dose * C-reactive protein (CRP) \> 30 mg/L (normal range \< 10 mg/L) 5. Naïve to canakinumab 6. Other protocol defined inclusion criteria may apply
Exclusion criteria
Patients who fulfilled one or more of the following criteria were not eligible for inclusion in this study: 1. Pregnant or nursing (lactating) female patients 2. Female patients having reached sexual maturity unless their career, lifestyle, or sexual orientation precluded intercourse with a male partner and/or they were using an acceptable method of contraception 3. History of hypersensitivity to study drug or to biologics. 4. Diagnosis of active macrophage-activation syndrome (MAS) (Ravelli, Magni-Manzoni and Pistorio 2005) within the last 6 months 5. With active or recurrent bacterial, fungal or viral infection, including patients with evidence of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C infection 6. Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria | Baseline, Day 15, Day 29 | Adapted ACR Pediatric 30 criteria determined responders (improved from baseline of at least 30% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2.Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4.Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Achieving the Adapted ACR Pediatric 70 | Baseline, Day 15, Day 29 | Adapted ACR Pediatric 70 criteria determined responders (improved from baseline of at least 70% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L) |
| Percentage of Patients Achieving the Adapted ACR Pediatric 90 | Baseline, Day 15, Day 29 | Adapted ACR Pediatric 90 criteria determined responders (improved from baseline of at least 90% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L) |
| Percentage of Patients Achieving the Adapted ACR Pediatric 100 | baseline, Day 15, Day 29 | Adapted ACR Pediatric 100 criteria determined responders (ie improved from baseline of at least 100% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation |
| Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ) | Baseline, Day 15 | CHAQ assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty' (0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement. |
| Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria | Baseline, Day 15, Day 29 | Adapted ACR Pediatric 50 criteria determined responders (improved from baseline of at least 50% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30%) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L) |
| Percentage of Patients Who Had Body Temperature ≤ 38°C | Day 3 | Body temperature was derived from vital signs evaluation. No conversion of body temperature was performed, no matter how it was measured. |
| Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50) | Over 4 week study period (Baseline, Day 15, Day 29) | CHQ-PF50 measures HRQoL in children 5-18 years old from parent's perspective. Questionnaire completed by parent without input from patient. Total score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents. Mixed linear model on change from baseline in CHQ-PF50 score with treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Covariance analysis used a repeated measures approach, so all timepoints over time were taken into account. |
| Change in Disability Score Over Time by Use of the CHAQ | At 4 week study period | The disability dimension of CHAQ consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). Mixed linear model on change from baseline in CHAQ score included treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Negative change indicates improvement. |
| Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ | Baseline, Day 29 | CHAQ, assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement. |
Countries
Argentina, Belgium, Brazil, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Norway, Peru, Poland, South Africa, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections. | 43 |
| Placebo Patients received a single dose matching placebo of canakinumab on day 1. | 41 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Unsatisfactory therapeutic effect | 6 | 37 |
Baseline characteristics
| Characteristic | Canakinumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 8.3 years STANDARD_DEVIATION 5.08 | 9.7 years STANDARD_DEVIATION 4.32 | 9.0 years STANDARD_DEVIATION 4.75 |
| Sex: Female, Male Female | 27 Participants | 23 Participants | 50 Participants |
| Sex: Female, Male Male | 16 Participants | 18 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 43 | 3 / 41 |
| serious Total, serious adverse events | 2 / 43 | 2 / 41 |
Outcome results
Primary
Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
Adapted ACR Pediatric 30 criteria determined responders (improved from baseline of at least 30% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2.Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4.Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)
Time frame: Baseline, Day 15, Day 29
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria | Day 15 | 83.7 percentage of participants |
| Canakinumab | Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria | Day 29 | 79.1 percentage of participants |
| Placebo | Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria | Day 15 | 9.8 percentage of participants |
| Placebo | Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria | Day 29 | 9.8 percentage of participants |
Secondary
Change in Disability Score Over Time by Use of the CHAQ
The disability dimension of CHAQ consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). Mixed linear model on change from baseline in CHAQ score included treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Negative change indicates improvement.
Time frame: At 4 week study period
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab | Change in Disability Score Over Time by Use of the CHAQ | -0.8 Units on a Scale | Standard Error 0.15 |
| Placebo | Change in Disability Score Over Time by Use of the CHAQ | -0.2 Units on a Scale | Standard Error 0.2 |
Secondary
Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50)
CHQ-PF50 measures HRQoL in children 5-18 years old from parent's perspective. Questionnaire completed by parent without input from patient. Total score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents. Mixed linear model on change from baseline in CHQ-PF50 score with treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Covariance analysis used a repeated measures approach, so all timepoints over time were taken into account.
Time frame: Over 4 week study period (Baseline, Day 15, Day 29)
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Observed cases only were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab | Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50) | CHQ-PF50 physical score | 16.9 units on a scale | Standard Error 3.46 |
| Canakinumab | Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50) | CHQ-PF50 psychosocial score | 6.2 units on a scale | Standard Error 2.15 |
| Placebo | Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50) | CHQ-PF50 physical score | 4.9 units on a scale | Standard Error 3.97 |
| Placebo | Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50) | CHQ-PF50 psychosocial score | -1.1 units on a scale | Standard Error 2.49 |
Secondary
Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ
CHAQ, assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.
Time frame: Baseline, Day 29
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab | Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ | 20.6 Units on a scale | Standard Error 5.59 |
| Placebo | Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ | 62.5 Units on a scale | Standard Error 9.7 |
Secondary
Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ)
CHAQ assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty' (0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.
Time frame: Baseline, Day 15
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab | Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ) | 20.3 Units on a scale | Standard Error 5.08 |
| Placebo | Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ) | 66.7 Units on a scale | Standard Error 6.35 |
Secondary
Percentage of Patients Achieving the Adapted ACR Pediatric 100
Adapted ACR Pediatric 100 criteria determined responders (ie improved from baseline of at least 100% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation
Time frame: baseline, Day 15, Day 29
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Patients Achieving the Adapted ACR Pediatric 100 | Day 15 | 32.6 percent of participants |
| Canakinumab | Percentage of Patients Achieving the Adapted ACR Pediatric 100 | Day 29 | 32.6 percent of participants |
| Placebo | Percentage of Patients Achieving the Adapted ACR Pediatric 100 | Day 15 | 0 percent of participants |
| Placebo | Percentage of Patients Achieving the Adapted ACR Pediatric 100 | Day 29 | 2.4 percent of participants |
Secondary
Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
Adapted ACR Pediatric 50 criteria determined responders (improved from baseline of at least 50% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30%) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)
Time frame: Baseline, Day 15, Day 29
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria | Day 15 | 67.4 percentage of participants |
| Canakinumab | Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria | Day 29 | 76.7 percentage of participants |
| Placebo | Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria | Day 15 | 4.9 percentage of participants |
| Placebo | Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria | Day 29 | 4.9 percentage of participants |
Secondary
Percentage of Patients Achieving the Adapted ACR Pediatric 70
Adapted ACR Pediatric 70 criteria determined responders (improved from baseline of at least 70% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)
Time frame: Baseline, Day 15, Day 29
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Patients Achieving the Adapted ACR Pediatric 70 | Day 15 | 60.5 percent of participants |
| Canakinumab | Percentage of Patients Achieving the Adapted ACR Pediatric 70 | Day 29 | 65.1 percent of participants |
| Placebo | Percentage of Patients Achieving the Adapted ACR Pediatric 70 | Day 15 | 2.4 percent of participants |
| Placebo | Percentage of Patients Achieving the Adapted ACR Pediatric 70 | Day 29 | 2.4 percent of participants |
Secondary
Percentage of Patients Achieving the Adapted ACR Pediatric 90
Adapted ACR Pediatric 90 criteria determined responders (improved from baseline of at least 90% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)
Time frame: Baseline, Day 15, Day 29
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Patients Achieving the Adapted ACR Pediatric 90 | Day 15 | 41.9 percent of participants |
| Canakinumab | Percentage of Patients Achieving the Adapted ACR Pediatric 90 | Day 29 | 46.5 percent of participants |
| Placebo | Percentage of Patients Achieving the Adapted ACR Pediatric 90 | Day 15 | 0 percent of participants |
| Placebo | Percentage of Patients Achieving the Adapted ACR Pediatric 90 | Day 29 | 2.4 percent of participants |
Secondary
Percentage of Patients Who Had Body Temperature ≤ 38°C
Body temperature was derived from vital signs evaluation. No conversion of body temperature was performed, no matter how it was measured.
Time frame: Day 3
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Percentage of Patients Who Had Body Temperature ≤ 38°C | 100 Percent of participants |
| Placebo | Percentage of Patients Who Had Body Temperature ≤ 38°C | 86.8 Percent of participants |