Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis
Brief summary
This study assesses the long-term safety and efficacy of adalimumab in pediatric subjects with ulcerative colitis.
Interventions
BIOLOGICALAdalimumab
every other week or weekly subcutaneous injection
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
\- Subject must have successfully enrolled and completed M11-290 study
Exclusion criteria
\- Subject considered by the investigator, for any reason, to be an unsuitable candidate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From first dose of study drug until 70 days following last dose of study drug (up to 298 weeks). | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug. |
| Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96,108,120, 144, 168, 192, 216, 240, 264, and 288 | The Partial Mayo Score (PMS) is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Physician's Global Assessment (PGA), scored from 0 (normal) to 3 (severe disease). The overall Partial Mayo score ranges from 0 to 9 with higher scores representing more severe disease. Clinical remission was defined as a PMS ≤ 2 and no individual subscore \> 1. |
| Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96,108,120, 144, 168, 192, 216, 240, 264, and 288 | The Partial Mayo Score (PMS) is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Physician's Global Assessment (PGA), scored from 0 (normal) to 3 (severe disease). The overall Partial Mayo score ranges from 0 to 9 with higher scores representing more severe disease. Clinical response was defined as a decrease in PMS ≥ 2 points and ≥ 30% from Study M11-290 Baseline. |
| Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96,108,120, 144, 168, 192, 216, 240, 264, and 288 | The Pediatric Ulcerative Colitis Activity Index (PUCAI) measures UC disease activity in children and adolescents by evaluating the following 6 areas: abdominal pain, number of stools per day, stool consistency, amount of blood in stools, nocturnal stooling, and activity level. The PUCAI score ranges from 0 to 85 with higher scores representing more severe disease. Recommended cut-off scores to differentiate disease activity are 0-9 (inactive), 10-34 (mild), 35-64 (moderate), and \> 65 (severe). Clinical remission was defined as a PUCAI score \< 10. |
| Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96,108,120, 144, 168, 192, 216, 240, 264, and 288 | The Pediatric Ulcerative Colitis Activity Index (PUCAI) measures UC disease activity in children and adolescents by evaluating the following 6 areas: abdominal pain, number of stools per day, stool consistency, amount of blood in stools, nocturnal stooling, and activity level. The PUCAI score ranges from 0 to 85 with higher scores representing more severe disease. Recommended cut-off scores to differentiate disease activity are 0-9 (inactive), 10-34 (mild), 35-64 (moderate), and \> 65 (severe). PUCAI response was defined as a decrease in PUCAI score ≥ 20 points from Study M11-290 Baseline. |
Countries
Japan, Poland, Slovakia, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab Participants received adalimumab every other week (EOW) or every week (EW) subcutaneous injection for up to 288 weeks.
(Prior to Amendment 4): Participants who enrolled into the study from blinded treatment in Study M11-290 received open-label adalimumab 0.6 mg/kg (maximum dose of 40 mg) EOW.
Participants who received open-label adalimumab 0.6 mg/kg (maximum of 40 mg) EW in Study M11-290 maintained the same dose in Study M10-870.
(After Amendment 4): Participants with a body weight \< 25 kg received open-label adalimumab 20 mg EOW.
Participants with a body weight ≥ 25 kg - \< 40 kg received open-label adalimumab 40 mg EOW.
Participants with a body weight ≥ 40 kg received open-label adalimumab 80 mg EOW. | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 18 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | other | 2 |
| Overall Study | Required alternative (or prohibited) therapy | 1 |
| Overall Study | Subject noncompliance | 3 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Adalimumab |
|---|---|
| Age, Continuous | 14.7 years STANDARD_DEVIATION 3.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 54 Participants |
| Proportion of Participants Who Achieve PUCAI Remission at Baseline | 42 Participants |
| Proportion of Participants Who Achieve PUCAI Response at Study M11-290 Baseline | 46 Participants |
| Proportion of Participants with Partial Mayo Score (PMS) Remission at Baseline | 46 Participants |
| Proportion of Participants with PMS Response at Study M11-290 Baseline | 54 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 52 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 59 |
| other Total, other adverse events | 54 / 59 |
| serious Total, serious adverse events | 16 / 59 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Time frame: From first dose of study drug until 70 days following last dose of study drug (up to 298 weeks).
Population: Integrated Full Analysis Set (IFAS) included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adalimumab | Number of Participants With Adverse Events (AEs) | Any TEAE | 55 Participants |
| Adalimumab | Number of Participants With Adverse Events (AEs) | TESAE | 15 Participants |
Primary
Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS)
The Partial Mayo Score (PMS) is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Physician's Global Assessment (PGA), scored from 0 (normal) to 3 (severe disease). The overall Partial Mayo score ranges from 0 to 9 with higher scores representing more severe disease. Clinical remission was defined as a PMS ≤ 2 and no individual subscore \> 1.
Time frame: Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96,108,120, 144, 168, 192, 216, 240, 264, and 288
Population: Integrated Full Analysis Set (IFAS) included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 8 | 47 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 24 | 43 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 36 | 45 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 48 | 40 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 120 | 33 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 216 | 29 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 240 | 28 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 264 | 27 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 4 | 50 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 12 | 51 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 60 | 42 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 72 | 42 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 84 | 40 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 96 | 36 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 108 | 37 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 144 | 32 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 168 | 31 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 192 | 30 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Remission as Measured by Partial Mayo Score (PMS) | Week 288 | 25 Participants |
Primary
Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline)
The Partial Mayo Score (PMS) is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Physician's Global Assessment (PGA), scored from 0 (normal) to 3 (severe disease). The overall Partial Mayo score ranges from 0 to 9 with higher scores representing more severe disease. Clinical response was defined as a decrease in PMS ≥ 2 points and ≥ 30% from Study M11-290 Baseline.
Time frame: Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96,108,120, 144, 168, 192, 216, 240, 264, and 288
Population: Integrated Full Analysis Set (IFAS) included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 144 | 35 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 264 | 28 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 288 | 26 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 4 | 56 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 8 | 55 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 12 | 56 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 24 | 51 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 36 | 50 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 48 | 47 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 60 | 46 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 72 | 44 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 84 | 43 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 96 | 42 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 108 | 40 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 120 | 39 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 168 | 35 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 192 | 32 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 216 | 30 Participants |
| Adalimumab | Proportion of Participants Who Achieve Clinical Response as Measured by PMS (From Study M11-290 Baseline) | Week 240 | 29 Participants |
Primary
Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission
The Pediatric Ulcerative Colitis Activity Index (PUCAI) measures UC disease activity in children and adolescents by evaluating the following 6 areas: abdominal pain, number of stools per day, stool consistency, amount of blood in stools, nocturnal stooling, and activity level. The PUCAI score ranges from 0 to 85 with higher scores representing more severe disease. Recommended cut-off scores to differentiate disease activity are 0-9 (inactive), 10-34 (mild), 35-64 (moderate), and \> 65 (severe). Clinical remission was defined as a PUCAI score \< 10.
Time frame: Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96,108,120, 144, 168, 192, 216, 240, 264, and 288
Population: Integrated Full Analysis Set (IFAS) included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 4 | 50 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 36 | 44 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 48 | 39 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 84 | 40 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 120 | 34 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 144 | 33 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 168 | 30 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 8 | 46 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 12 | 50 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 24 | 42 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 60 | 38 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 72 | 42 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 96 | 37 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 108 | 37 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 192 | 28 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 216 | 28 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 240 | 27 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 264 | 26 Participants |
| Adalimumab | Proportion of Participants Who Achieve Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission | Week 288 | 24 Participants |
Primary
Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline)
The Pediatric Ulcerative Colitis Activity Index (PUCAI) measures UC disease activity in children and adolescents by evaluating the following 6 areas: abdominal pain, number of stools per day, stool consistency, amount of blood in stools, nocturnal stooling, and activity level. The PUCAI score ranges from 0 to 85 with higher scores representing more severe disease. Recommended cut-off scores to differentiate disease activity are 0-9 (inactive), 10-34 (mild), 35-64 (moderate), and \> 65 (severe). PUCAI response was defined as a decrease in PUCAI score ≥ 20 points from Study M11-290 Baseline.
Time frame: Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96,108,120, 144, 168, 192, 216, 240, 264, and 288
Population: Integrated Full Analysis Set (IFAS) included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 48 | 38 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 96 | 37 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 108 | 36 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 120 | 34 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 144 | 32 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 168 | 30 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 192 | 27 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 216 | 25 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 240 | 26 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 4 | 47 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 8 | 47 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 12 | 49 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 24 | 42 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 36 | 43 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 60 | 39 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 72 | 40 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 84 | 37 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 264 | 23 Participants |
| Adalimumab | Proportion of Participants Who Achieve PUCAI Response (From Study M11-290 Baseline) | Week 288 | 21 Participants |