Atopic Dermatitis
Conditions
Keywords
Atopic, dermatitis, asthma, children, modification, Atopic dermatitis/atopy
Brief summary
This study consists of a 3-year double-blind phase during which patients will receive atopic dermatitis (AD) treatment either with pimecrolimus cream 1% long-term management (LTM) or with a conventional corticosteroid-based treatment (1:1 ratio), followed by a 2 to 3-year open-label (OL) phase (all patients receiving pimecrolimus cream 1% LTM). At the end of the double-blind phase, the two treatment groups will be compared with respect to their efficacy in controlling AD; at the end of the OL phase, the incidence of asthma at the age of 6 years will be compared.
Interventions
DRUGPimecrolimus
Pimecrolimus cream 1 %
DRUGCorticosteroid
conventional corticosteroid-based treatment
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Months to 18 Months
Healthy volunteers
No
Inclusion criteria
* Diagnosis of atopic dermatitis * Family history of atopy * 3 to 18 months of age at baseline * At least mild atopic dermatitis at baseline (investigator global assessment \[IGA\] greater or equal to 2) * Clinical evidence of atopic dermatitis for no longer than 3 months
Exclusion criteria
* Diagnosis of or substantial clinical evidence for food or other allergies at baseline Other protocol related criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Atopic Dermatitis (AD) Disease Control Over 36 Months | 36 months | Proportion of disease-free days in Step 2 or less (per Patient) using total number of days in study as the denominator- double-blind phase. Intent to Treat Population: defined as all randomized patients who were dispensed study medication and had at least one post baseline efficacy measurement. |
| Effect of Early Use of Pimecrolimus Cream 1% in Reducing the Incidence of Asthma at 6 Years of Age | 6 years | Note: The results for this efficacy variable are not reported due to early termination of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Corticosteroid and Pimecrolimus Drug Use | 48 months | Corticosteroid and pimecrolimus study medication days of exposure during the 36 month double-blind phase. Note: Although the double-blind phase was designed to be 36 months (3 years) in length, the last double-blind visit for some patients occurred after 36 months. |
| Long Term Safety in Infants and Young Children | 6 years | Note: The results of this secondary outcome is not reported due to early termination of the study. |
| Patient/Caregiver Quality of Life | From Baseline to Visit 5 , 6, 8, 10, 12, and 14 | Change from Baseline in the total Parents' Index of Quality of Life-Atopic Dermatitis (PIQoL-AD) score in the double-blind phase. PIQoL-AD Score = (sum of valid items/number of valid items) \* 28. Scores range from a minimum value of 0 to a maximum value of 28 with a high total overall score indicating poor quality of life. |
| Atopic Dermatitis (AD) Remission Time | 36 month Double-Blind Phase | Longest duration of atopic dermatitis (AD) remission during the 36 month double-blind treatment phase. A remission day was defined as a diary day with a positive response (yes) to the question No or almost no eczema? and a response of no treatment except emollients to the question Medication used. |
| Incidence of Allergic Rhinitis, Allergic Conjunctivitis and Food Allergies | 6 years (36 month Double-Blind Phase) | Percentage of Patients who had allergic rhinitis, allergic conjunctivitis and food allergies at the end of the 36 month double blind study. Note: The results at six years are not reported due to early termination of the study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pimecrolimus (Elidel) Treatment Group Pimecrolimus (Elidel) 1% Cream twice a day/topical corticosteroid rescue | 543 |
| Control Treatment Group Management with vehicle/topical corticosteroid rescue. | 544 |
| Total | 1,087 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lack of Efficacy | 5 | 10 |
| Overall Study | Lost to Follow-up | 114 | 120 |
| Overall Study | Protocol Violation | 3 | 5 |
| Overall Study | Randomized but did not take medication | 3 | 1 |
| Overall Study | Withdrawal by Subject | 127 | 136 |
Baseline characteristics
| Characteristic | Pimecrolimus (Elidel) Treatment Group | Control Treatment Group | Total |
|---|---|---|---|
| Age Continuous | 7.1 months STANDARD_DEVIATION 3.76 | 7.4 months STANDARD_DEVIATION 4.06 | 7.3 months STANDARD_DEVIATION 3.91 |
| Age, Customized 12 months to Less than or equal to 18 months | 81 Participants | 99 Participants | 180 Participants |
| Age, Customized 3 months to Less than 6 months | 230 Participants | 223 Participants | 453 Participants |
| Age, Customized 6 months to Less than 12 months | 231 Participants | 220 Participants | 451 Participants |
| Age, Customized Greater than 18 months | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Less than 3 months | 1 Participants | 2 Participants | 3 Participants |
| Parents' Index of Quality of Life - Atopic Dermatitis Score | 6.5 Scores on PIQoL-AD Scale STANDARD_DEVIATION 4.73 | 6.9 Scores on PIQoL-AD Scale STANDARD_DEVIATION 4.92 | 6.7 Scores on PIQoL-AD Scale STANDARD_DEVIATION 4.83 |
| Sex: Female, Male Female | 194 Participants | 218 Participants | 412 Participants |
| Sex: Female, Male Male | 349 Participants | 326 Participants | 675 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 482 / 543 | 467 / 544 |
| serious Total, serious adverse events | 42 / 543 | 37 / 544 |
Outcome results
Primary
Atopic Dermatitis (AD) Disease Control Over 36 Months
Proportion of disease-free days in Step 2 or less (per Patient) using total number of days in study as the denominator- double-blind phase. Intent to Treat Population: defined as all randomized patients who were dispensed study medication and had at least one post baseline efficacy measurement.
Time frame: 36 months
Population: Intent to Treat Population: all randomized patients who were dispensed study medication and had at least one post baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pimecrolimus (Elidel) Treatment Group | Atopic Dermatitis (AD) Disease Control Over 36 Months | 0.4404 Proportion of disease free days | Standard Deviation 0.29876 |
| Control Treatment Group | Atopic Dermatitis (AD) Disease Control Over 36 Months | 0.4346 Proportion of disease free days | Standard Deviation 0.29317 |
Comparison: A disease-free day in Step 2 or less was defined as a diary day with variable No or almost no eczema?=yes and medication used variable=no except emollients, yellow label medication 2X day, or medication deviation of yellow label medication 1x day.p-value: 0.790195% CI: [-0.029, 0.0381]ANCOVA
Primary
Effect of Early Use of Pimecrolimus Cream 1% in Reducing the Incidence of Asthma at 6 Years of Age
Note: The results for this efficacy variable are not reported due to early termination of the study.
Time frame: 6 years
Secondary
Atopic Dermatitis (AD) Remission Time
Longest duration of atopic dermatitis (AD) remission during the 36 month double-blind treatment phase. A remission day was defined as a diary day with a positive response (yes) to the question No or almost no eczema? and a response of no treatment except emollients to the question Medication used.
Time frame: 36 month Double-Blind Phase
Population: Intent-to-Treat population: all randomized patients who were dispensed study medication and had at least one post baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pimecrolimus (Elidel) Treatment Group | Atopic Dermatitis (AD) Remission Time | 105.9547 Days | Standard Deviation 137.6135 |
| Control Treatment Group | Atopic Dermatitis (AD) Remission Time | 117.1071 Days | Standard Deviation 150.33993 |
Secondary
Corticosteroid and Pimecrolimus Drug Use
Corticosteroid and pimecrolimus study medication days of exposure during the 36 month double-blind phase. Note: Although the double-blind phase was designed to be 36 months (3 years) in length, the last double-blind visit for some patients occurred after 36 months.
Time frame: 48 months
Population: Safety population: all randomized patients who were dispensed study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimecrolimus (Elidel) Treatment Group | Corticosteroid and Pimecrolimus Drug Use | 0-12 months (Year 1) | 146.6 Days of Exposure | Standard Deviation 105.75 |
| Pimecrolimus (Elidel) Treatment Group | Corticosteroid and Pimecrolimus Drug Use | 25-36 months (Year 3) | 42.2 Days of Exposure | Standard Deviation 83.65 |
| Pimecrolimus (Elidel) Treatment Group | Corticosteroid and Pimecrolimus Drug Use | 13-24 months (Year 2) | 75.0 Days of Exposure | Standard Deviation 105.08 |
| Pimecrolimus (Elidel) Treatment Group | Corticosteroid and Pimecrolimus Drug Use | 37-48 months (Year 4) | 1.1 Days of Exposure | Standard Deviation 5.74 |
| Pimecrolimus (Elidel) Treatment Group | Corticosteroid and Pimecrolimus Drug Use | Double -blind phase | 264.8 Days of Exposure | Standard Deviation 259.49 |
| Control Treatment Group | Corticosteroid and Pimecrolimus Drug Use | 37-48 months (Year 4) | 1.0 Days of Exposure | Standard Deviation 5.34 |
| Control Treatment Group | Corticosteroid and Pimecrolimus Drug Use | Double -blind phase | 249.6 Days of Exposure | Standard Deviation 251.71 |
| Control Treatment Group | Corticosteroid and Pimecrolimus Drug Use | 0-12 months (Year 1) | 147.6 Days of Exposure | Standard Deviation 112.69 |
| Control Treatment Group | Corticosteroid and Pimecrolimus Drug Use | 13-24 months (Year 2) | 65.0 Days of Exposure | Standard Deviation 97.42 |
| Control Treatment Group | Corticosteroid and Pimecrolimus Drug Use | 25-36 months (Year 3) | 36.6 Days of Exposure | Standard Deviation 76.31 |
Secondary
Incidence of Allergic Rhinitis, Allergic Conjunctivitis and Food Allergies
Percentage of Patients who had allergic rhinitis, allergic conjunctivitis and food allergies at the end of the 36 month double blind study. Note: The results at six years are not reported due to early termination of the study.
Time frame: 6 years (36 month Double-Blind Phase)
Population: Intent to Treat Population defined as all randomized patients who were dispensed study medication and had at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pimecrolimus (Elidel) Treatment Group | Incidence of Allergic Rhinitis, Allergic Conjunctivitis and Food Allergies | Diagnosis of Food Allergy | 16.1 Percentage of Participants |
| Pimecrolimus (Elidel) Treatment Group | Incidence of Allergic Rhinitis, Allergic Conjunctivitis and Food Allergies | Diagnosis of Allergic rhinitis | 18.6 Percentage of Participants |
| Pimecrolimus (Elidel) Treatment Group | Incidence of Allergic Rhinitis, Allergic Conjunctivitis and Food Allergies | Diagnosis of Allergic conjunctivitis | 12.4 Percentage of Participants |
| Control Treatment Group | Incidence of Allergic Rhinitis, Allergic Conjunctivitis and Food Allergies | Diagnosis of Food Allergy | 13.2 Percentage of Participants |
| Control Treatment Group | Incidence of Allergic Rhinitis, Allergic Conjunctivitis and Food Allergies | Diagnosis of Allergic rhinitis | 16.4 Percentage of Participants |
| Control Treatment Group | Incidence of Allergic Rhinitis, Allergic Conjunctivitis and Food Allergies | Diagnosis of Allergic conjunctivitis | 10.5 Percentage of Participants |
Secondary
Long Term Safety in Infants and Young Children
Note: The results of this secondary outcome is not reported due to early termination of the study.
Time frame: 6 years
Secondary
Patient/Caregiver Quality of Life
Change from Baseline in the total Parents' Index of Quality of Life-Atopic Dermatitis (PIQoL-AD) score in the double-blind phase. PIQoL-AD Score = (sum of valid items/number of valid items) \* 28. Scores range from a minimum value of 0 to a maximum value of 28 with a high total overall score indicating poor quality of life.
Time frame: From Baseline to Visit 5 , 6, 8, 10, 12, and 14
Population: Intent-to-Treat Population: all randomized patients who were dispensed study medication and had at least one post baseline efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimecrolimus (Elidel) Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 5 (Week 14) | -2.6 Scores on PIQoL-AD Scale | Standard Deviation 3.67 |
| Pimecrolimus (Elidel) Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 6 (Week 27) | -2.7 Scores on PIQoL-AD Scale | Standard Deviation 3.84 |
| Pimecrolimus (Elidel) Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 8 (Week 53) | -2.9 Scores on PIQoL-AD Scale | Standard Deviation 3.97 |
| Pimecrolimus (Elidel) Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 10 (Week 88) | -3.1 Scores on PIQoL-AD Scale | Standard Deviation 4.13 |
| Pimecrolimus (Elidel) Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 12 (Week 122) | -3.3 Scores on PIQoL-AD Scale | Standard Deviation 4.15 |
| Pimecrolimus (Elidel) Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 14 (Week 158) | -3.5 Scores on PIQoL-AD Scale | Standard Deviation 4.28 |
| Control Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 12 (Week 122) | -3.6 Scores on PIQoL-AD Scale | Standard Deviation 4.39 |
| Control Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 5 (Week 14) | -2.3 Scores on PIQoL-AD Scale | Standard Deviation 3.37 |
| Control Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 10 (Week 88) | -3.5 Scores on PIQoL-AD Scale | Standard Deviation 4.23 |
| Control Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 6 (Week 27) | -2.7 Scores on PIQoL-AD Scale | Standard Deviation 3.83 |
| Control Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 14 (Week 158) | -3.8 Scores on PIQoL-AD Scale | Standard Deviation 4.35 |
| Control Treatment Group | Patient/Caregiver Quality of Life | Change in Baseline to Visit 8 (Week 53) | -3.1 Scores on PIQoL-AD Scale | Standard Deviation 4.23 |