Psoriasis
Conditions
Keywords
Pediatric Psoriasis
Brief summary
This study will evaluate the safety and efficacy of etanercept (Enbrel®) in children with Psoriasis.
Detailed description
On enrollment, participants underwent randomization in a 1:1 ratio to receive placebo or etanercept during the initial double-blind period. Participants could enter an escape group and receive open-label etanercept until week 12 if, at or after week 4, their Psoriasis Area and Severity Index (PASI) score either increased by more than 50% over baseline and by a minimum of 4 points at one visit or increased by more than 25% and by a minimum of 4 points at each of two consecutive visits. During the open-label treatment period, all patients (including those who entered the escape group) received open-label etanercept. Participants who did not achieve PASI 50 at week 24 or PASI 75 at week 36 could discontinue the study or add topical standard-of-care therapy (low-to-moderate-potency topical corticosteroids) and continue to receive open-label etanercept until week 48. At week 36, participants with PASI 50 at week 24 or PASI 75 at week 36 were randomly assigned to placebo or etanercept for 12 weeks in the withdrawal period. Participants in whom PASI 75 was lost resumed open-label etanercept through week 48 in the re-treatment period.
Interventions
DRUGEtanercept
Etanercept 0.8 mg/kg (up to an intended dose of 50 mg) by subcutaneous injection once a week
DRUGPlacebo
Placebo matching to etanercept administered by subcutaneous injection once a week
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patients with plaque psoriasis * Patient may not receive certain psoriasis medications during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI 75) at Week 12 | Baseline and week 12 | The percentage of participants who achieved 75% or greater improvement (decrease) from baseline in PASI score after 12 weeks of treatment. The PASI score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Participants who entered the escape arm or had missing data at week 12 were considered non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) at Week 12 | Week 12 | The sPGA is a static measurement based on induration, erythema, and scaling. The sPGA is assessed on a scale from 0 to 5: 0 = clear (no evidence of plaque elevation, erythema or scaling) 1. = almost clear (minimal plaque elevation, erythema or scaling) 2. = mild (mild plaque elevation or scaling, light red coloration) 3. = moderate (moderate plaque elevation, scaling, light red coloration) 4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration) 5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration). Participants who entered the escape arm or had missing data at week 12 were considered non-responders. |
| Percent Improvement From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 12 | Baseline and week 12 | The Children's Dermatology Life Quality Index (CDLQI) was used to assess the impact of psoriasis on subject health-related quality of life. The CDLQI has 10 items assessing health-related quality of life (HRQOL) in patients with skin disease each measured on a scale from 0 (Not at all) to 3 (Very much). The total score ranges from 0 to 30, with lower scores indicating better quality of life. If participants were ≥ 13 years old, the text instrument was completed by the participants themselves. Participants ≥ 8 but \< 13 years old used the cartoon version of the instrument and participants ≤ 7 years old used the cartoon version of the instrument completed with help from the parents or caregivers. Percent improvement from baseline = (Baseline Value - Post-baseline Value) / Baseline Value \* 100. Participants who entered the escape arm or who had missing data at week 12 were considered to have 0% improvement from baseline. |
| Percentage of Participants Achieving a ≥ 50% Improvement in PASI Score (PASI 50) at Week 12 | Baseline and week 12 | The percentage of participants who achieved 50% or greater improvement from baseline in PASI score after 12 weeks of treatment. PASI is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Participants who entered the escape arm or had missing data at week 12 were considered non-responders. |
| Number of Participants With Adverse Events During the Double-blind Treatment Period | 12 weeks | The severity assessment for adverse events and infections was done using the Common Toxicity Criteria (CTC) Version 2.0, where Grade 0 = no toxicity, Grade 1 = mild toxicity, Grade 2 = moderate toxicity, Grade 3 = severe toxicity, Grade 4 = life-threatening toxicity. Serious adverse events were any events that suggested a significant hazard or side effect, regardless of the investigator's or sponsor's opinion on the relationship to study medication. These included, but were not limited to, events at any dose that were fatal, life threatening, required in-patient hospitalization or prolonged hospitalization, were a persistent or significant disability/incapacity, or were a congenital abnormality/birth defect. Medical events that jeopardized a participant, required intervention to prevent one of the above outcomes, or resulted in urgent investigation could be considered serious. |
| Etanercept Serum Concentration | Day 1 (predose), week 12, week 24, and week 48 | Serum concentrations for etanercept were measured by using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 0.627 ng/mL. |
| Percentage of Participants Achieving a ≥ 90% Improvement in PASI Score (PASI 90) at Week 12 | Baseline and week 12 | The percentage of participants who achieved 90% or greater improvement from baseline in PASI score after 12 weeks of treatment. The PASI score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Participants who entered the escape arm or had missing data at week 12 were considered non-responders. |
Participant flow
Recruitment details
This 48-week study was conducted at 42 sites in the United States and Canada. The first participant was enrolled on September 8, 2004, and the last participant on November 29, 2005.
Pre-assignment details
On enrollment, participants underwent randomization at a 1:1 ratio by an interactive voice-response system.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to receive placebo administered by subcutaneous injection once a week during the 12-week, double-blind, placebo-controlled treatment period (day 1 to week 12). | 105 |
| Etanercept Participants randomized to receive 0.8 mg/kg etanercept administered by subcutaneous injection once a week during the 12-week, double-blind, placebo-controlled treatment period (day 1 to week 12). | 106 |
| Total | 211 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Treatment Period: Week 1-12 | Adverse Event | 0 | 1 | 0 | 0 |
| Double-blind Treatment Period: Week 1-12 | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Open-label Treatment Period: Weeks 13-36 | Adverse Event | 3 | 2 | 0 | 0 |
| Open-label Treatment Period: Weeks 13-36 | Incomplete Responders | 34 | 25 | 0 | 0 |
| Open-label Treatment Period: Weeks 13-36 | Lost to Follow-up | 1 | 1 | 0 | 0 |
| Open-label Treatment Period: Weeks 13-36 | Withdrawal by Subject | 2 | 2 | 0 | 0 |
| Withdrawal Period: Weeks 37-48 | Entered Retreatment | 0 | 0 | 29 | 13 |
| Withdrawal Period: Weeks 37-48 | Lost to Follow-up | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Etanercept | Total |
|---|---|---|---|
| Age, Continuous | 13.00 years | 14.00 years | 13.00 years |
| Age, Customized 12 to 17 years | 67 Participants | 68 Participants | 135 Participants |
| Age, Customized 4 to 11 years | 38 Participants | 38 Participants | 76 Participants |
| Duration of Psoriasis | 5.80 years | 6.80 years | 5.90 years |
| Psoriasis Area and Severity Index (PASI) | 16.40 units on a scale | 16.70 units on a scale | 16.40 units on a scale |
| Race/Ethnicity, Customized Asian | 6 Participants | 9 Participants | 15 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 3 Participants | 11 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 14 Participants | 8 Participants | 22 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 75 Participants | 83 Participants | 158 Participants |
| Sex: Female, Male Female | 52 Participants | 51 Participants | 103 Participants |
| Sex: Female, Male Male | 53 Participants | 55 Participants | 108 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 105 | 59 / 106 | 10 / 32 | 174 / 208 | 54 / 59 | 23 / 69 | 26 / 68 | 9 / 30 | 8 / 12 |
| serious Total, serious adverse events | 0 / 105 | 0 / 106 | 0 / 32 | 0 / 208 | 0 / 59 | 0 / 69 | 0 / 68 | 0 / 30 | 0 / 12 |
Outcome results
Primary
Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI 75) at Week 12
The percentage of participants who achieved 75% or greater improvement (decrease) from baseline in PASI score after 12 weeks of treatment. The PASI score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Participants who entered the escape arm or had missing data at week 12 were considered non-responders.
Time frame: Baseline and week 12
Population: The intent-to-treat population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI 75) at Week 12 | 11.0 percentage of participants |
| Etanercept | Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI 75) at Week 12 | 57.0 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Etanercept Serum Concentration
Serum concentrations for etanercept were measured by using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 0.627 ng/mL.
Time frame: Day 1 (predose), week 12, week 24, and week 48
Population: Participants assigned to etanercept at any time during the study, with available data.~Week 12 excludes participants assigned to placebo who escaped to etanercept. Week 48 includes participants randomized to etanercept at week 36 and remaining on etanercept to week 48. Participants randomized to placebo and retreated with etanercept are excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Etanercept Serum Concentration | Day 1 | 1.50 ng/mL | Standard Deviation 3.13 |
| Placebo | Etanercept Serum Concentration | Week 12 | 1614 ng/mL | Standard Deviation 828 |
| Placebo | Etanercept Serum Concentration | Week 24 | 2104 ng/mL | Standard Deviation 1255 |
| Placebo | Etanercept Serum Concentration | Week 48 | 1650 ng/mL | Standard Deviation 1126 |
Secondary
Number of Participants With Adverse Events During the Double-blind Treatment Period
The severity assessment for adverse events and infections was done using the Common Toxicity Criteria (CTC) Version 2.0, where Grade 0 = no toxicity, Grade 1 = mild toxicity, Grade 2 = moderate toxicity, Grade 3 = severe toxicity, Grade 4 = life-threatening toxicity. Serious adverse events were any events that suggested a significant hazard or side effect, regardless of the investigator's or sponsor's opinion on the relationship to study medication. These included, but were not limited to, events at any dose that were fatal, life threatening, required in-patient hospitalization or prolonged hospitalization, were a persistent or significant disability/incapacity, or were a congenital abnormality/birth defect. Medical events that jeopardized a participant, required intervention to prevent one of the above outcomes, or resulted in urgent investigation could be considered serious.
Time frame: 12 weeks
Population: The safety population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Grade 3 infection | 0 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Any adverse event | 62 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Non-infectious AE leading to withdrawal from Study | 0 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Infection leading to withdrawal from Study | 0 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Non-infectious adverse event | 46 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Injection site reaction | 5 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Serious non-infectious adverse event | 0 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Serious infection | 0 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Infection | 33 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Death | 0 Participants |
| Placebo | Number of Participants With Adverse Events During the Double-blind Treatment Period | Grade 3 non-infectious adverse event | 3 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Grade 3 infection | 0 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Serious non-infectious adverse event | 0 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Non-infectious adverse event | 42 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Non-infectious AE leading to withdrawal from Study | 1 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Any adverse event | 68 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Serious infection | 0 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Infection leading to withdrawal from Study | 0 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Grade 3 non-infectious adverse event | 0 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Infection | 50 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Injection site reaction | 7 Participants |
| Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Death | 0 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Injection site reaction | 1 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Death | 0 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Non-infectious adverse event | 9 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Infection | 9 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Serious non-infectious adverse event | 0 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Serious infection | 0 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Grade 3 non-infectious adverse event | 0 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Grade 3 infection | 0 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Non-infectious AE leading to withdrawal from Study | 0 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Infection leading to withdrawal from Study | 0 Participants |
| Escape: Etanercept | Number of Participants With Adverse Events During the Double-blind Treatment Period | Any adverse event | 16 Participants |
Secondary
Percentage of Participants Achieving a ≥ 50% Improvement in PASI Score (PASI 50) at Week 12
The percentage of participants who achieved 50% or greater improvement from baseline in PASI score after 12 weeks of treatment. PASI is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Participants who entered the escape arm or had missing data at week 12 were considered non-responders.
Time frame: Baseline and week 12
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a ≥ 50% Improvement in PASI Score (PASI 50) at Week 12 | 23 percentage of participants |
| Etanercept | Percentage of Participants Achieving a ≥ 50% Improvement in PASI Score (PASI 50) at Week 12 | 75 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving a ≥ 90% Improvement in PASI Score (PASI 90) at Week 12
The percentage of participants who achieved 90% or greater improvement from baseline in PASI score after 12 weeks of treatment. The PASI score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Participants who entered the escape arm or had missing data at week 12 were considered non-responders.
Time frame: Baseline and week 12
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a ≥ 90% Improvement in PASI Score (PASI 90) at Week 12 | 7 percentage of participants |
| Etanercept | Percentage of Participants Achieving a ≥ 90% Improvement in PASI Score (PASI 90) at Week 12 | 27 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) at Week 12
The sPGA is a static measurement based on induration, erythema, and scaling. The sPGA is assessed on a scale from 0 to 5: 0 = clear (no evidence of plaque elevation, erythema or scaling) 1. = almost clear (minimal plaque elevation, erythema or scaling) 2. = mild (mild plaque elevation or scaling, light red coloration) 3. = moderate (moderate plaque elevation, scaling, light red coloration) 4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration) 5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration). Participants who entered the escape arm or had missing data at week 12 were considered non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) at Week 12 | 13 percentage of participants |
| Etanercept | Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) at Week 12 | 53 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percent Improvement From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 12
The Children's Dermatology Life Quality Index (CDLQI) was used to assess the impact of psoriasis on subject health-related quality of life. The CDLQI has 10 items assessing health-related quality of life (HRQOL) in patients with skin disease each measured on a scale from 0 (Not at all) to 3 (Very much). The total score ranges from 0 to 30, with lower scores indicating better quality of life. If participants were ≥ 13 years old, the text instrument was completed by the participants themselves. Participants ≥ 8 but \< 13 years old used the cartoon version of the instrument and participants ≤ 7 years old used the cartoon version of the instrument completed with help from the parents or caregivers. Percent improvement from baseline = (Baseline Value - Post-baseline Value) / Baseline Value \* 100. Participants who entered the escape arm or who had missing data at week 12 were considered to have 0% improvement from baseline.
Time frame: Baseline and week 12
Population: Intent-to-treat population with available CDLQI data at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Improvement From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 12 | 17.5 percent improvement | Standard Error 8.3 |
| Etanercept | Percent Improvement From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 12 | 52.3 percent improvement | Standard Error 6.1 |
p-value: <0.0001Van Elteren test