Psoriasis
Conditions
Brief summary
The purpose of this study is to evaluate the potential of DFD-06 to suppress the hypothalamic-pituitary-adrenal (HPA) axis when applied twice daily for 15 days.
Detailed description
This is a 15-day, single arm, multicenter, multi-dose, open-label, two stage, sequential study. In the first stage, subjects who are at least 12 years of age and not more than 16.9 years (16 years and 11 months) of age with moderate to severe plaque psoriasis will be treated with DFD-06 (at least 20 completed subjects). In the second stage subjects who are at least 6 years of age and not more than 11.9 years (11 years and 11 months) of age with moderate to severe plaque psoriasis will be treated with DFD-06 (at least 20 completed subjects). An attempt will be made to enroll subjects throughout the age range of each cohort including the lower age range. DFD-06 will be applied twice daily to all affected areas on the body excluding face, scalp, groin, axillae and other intertriginous areas. Subjects must have ≥10% Body Surface Area (BSA) treated to achieve maximal use exposure.
Interventions
DRUGDFD06
Apply twice per day for 15 days
Sponsors
Prosoft Clinical
Primus Pharmaceuticals
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In the first stage, subjects who are at least 12 years of age and not more than 16.9 years (16 years and 11 months) of age with moderate to severe plaque psoriasis will be treated with DFD-06 (at least 20 completed subjects). In the second stage subjects who are at least 6 years of age and not more than 11.9 years (11 years and 11 months) of age with moderate to severe plaque psoriasis will be treated with DFD-06 (at least 20 completed subjects).
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects and the parent or legal guardian understand the study procedures and agree to participate by giving assent and written informed consent, respectively. Subject's parent or legal guardian must be willing to authorize use and disclosure of protected health information collected for the study. * Subjects must be at least 6 years and not more than 16.9 years of age, with body weight greater than or equal to 45 pounds at Screening. * Subjects must present with a clinical diagnosis of stable (at least 3 months) plaque psoriasis. * Subjects with psoriasis involving ≥10% Body Surface Area (BSA), not including the face, scalp, groin, axillae and other intertriginous areas at the Baseline Visit. * Subjects must have an Investigator Global Assessment (IGA) grade of at least 3 (moderate) at the Baseline Visit.
Exclusion criteria
* Subject has a current diagnosis of unstable forms of psoriasis including guttate, erythrodermic, exfoliative or pustular psoriasis. * Subject has a history of organ transplant requiring immunosuppression, HIV, or other immunocompromised state. * Subject has received treatment for any type of cancer within 5 years of the Baseline Visit except skin cancer and cervical cancer (in situ) are allowed if at least 1 year before the Baseline Visit. * Subject has a history or presence of intracranial hypertension. * Subject has had prolonged exposure to natural or artificial sources of ultraviolet radiation within 30 days prior to the initiation of treatment or is intending to have such exposure during the study that is thought by the investigator to likely modify the subject's disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With HPA Axis Suppression at Day 15 | Day 15 | The percentage of subjects with abnormal cortisol response for ACTH stimulation test at Day 15 (cortisol level ≤18 µg/dL at 30 minutes post stimulation) is the primary variable |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement in IGA Grade From Baseline | Baseline up to Day 15 | Numbers of subjects with improvements by at least 1 pint in IGA grade will be provided as descriptive statistics. |
| Plasma Concentration of Clobetasol Propionate | Day 15 0 hour, 1 hour, 3 hours, 6 hours after application | Plasma concentrations of clobetasol propionate after multiple doses of DFD-06 under maximal use condition with the final-to-be-marketed formulation. |
Countries
United States
Participant flow
Pre-assignment details
Normal response to cosyntropin stimulation defined as a Screening Cosyntropin Stimulation Test (CST) with a 30-minute post-stimulation cortisol level of \> 18 ug/dL.
Participants by arm
| Arm | Count |
|---|---|
| DFD-06 Cream This is a single arm, open label study and there will be no reference or control product used in this study
DFD06: Apply twice per day for 15 days | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | DFD-06 Cream |
|---|---|
| Age, Continuous | 14.2 years STANDARD_DEVIATION 1.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Investigator Global Assessment | 3 units on a scale STANDARD_DEVIATION 0 |
| Percent Body Surface Area Affected | 14.2 percent body surface area |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 5 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 | 17 Participants |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 8 / 22 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
Percentage of Subjects With HPA Axis Suppression at Day 15
The percentage of subjects with abnormal cortisol response for ACTH stimulation test at Day 15 (cortisol level ≤18 µg/dL at 30 minutes post stimulation) is the primary variable
Time frame: Day 15
Population: The Evaluable population included those subjects in the Safety population who had both Screening and Day 15 serum cortisol data (pre- and post-cosyntropin stimulation) and had a normal response to Screening Cosyntropin Stimulation Test with a 30-minute post-stimulation cortisol level of \> 18 μg/dL and applied at least 80% of expected (29) applications
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DFD-06 Cream | Percentage of Subjects With HPA Axis Suppression at Day 15 | 3 Participants |
Secondary
Number of Participants With Improvement in IGA Grade From Baseline
Numbers of subjects with improvements by at least 1 pint in IGA grade will be provided as descriptive statistics.
Time frame: Baseline up to Day 15
Population: The Evaluable population included those subjects in the Safety population who had both Screening and Day 15 serum cortisol data (pre- and post-cosyntropin stimulation) and had a normal response to Screening Cosyntropin Stimulation Test with a 30-minute post-stimulation cortisol level of \> 18 μg/dL and applied at least 80% of expected (29) applications
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DFD-06 Cream | Number of Participants With Improvement in IGA Grade From Baseline | Day 8 1-point improvement in IGA | 15 participants |
| DFD-06 Cream | Number of Participants With Improvement in IGA Grade From Baseline | Day 8 2-point improvement in IGA | 2 participants |
| DFD-06 Cream | Number of Participants With Improvement in IGA Grade From Baseline | Day 15 1 point improvement in IGA | 8 participants |
| DFD-06 Cream | Number of Participants With Improvement in IGA Grade From Baseline | Day 15 2-point improvement in IGA | 10 participants |
| DFD-06 Cream | Number of Participants With Improvement in IGA Grade From Baseline | Day 15 3-point improvement in IGA | 2 participants |
Secondary
Plasma Concentration of Clobetasol Propionate
Plasma concentrations of clobetasol propionate after multiple doses of DFD-06 under maximal use condition with the final-to-be-marketed formulation.
Time frame: Day 15 0 hour, 1 hour, 3 hours, 6 hours after application
Population: The Evaluable population included those subjects in the Safety population who had both Screening and Day 15 serum cortisol data (pre- and post-cosyntropin stimulation) and had a normal response to Screening Cosyntropin Stimulation Test with a 30-minute post-stimulation cortisol level of \> 18 μg/dL and applied at least 80% of expected (29) applications.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DFD-06 Cream | Plasma Concentration of Clobetasol Propionate | 1 hour clobetasol plasma level | 40.370 pg/mL | Standard Deviation 32.55 |
| DFD-06 Cream | Plasma Concentration of Clobetasol Propionate | 3 hour clobetasol plasma level | 64.250 pg/mL | Standard Deviation 41.93 |
| DFD-06 Cream | Plasma Concentration of Clobetasol Propionate | 6 hour clobetasol plasma level | 42.143 pg/mL | Standard Deviation 27.32 |
| DFD-06 Cream | Plasma Concentration of Clobetasol Propionate | 0 hour clobetasol plasma level | 51.486 pg/mL | Standard Deviation 48.35 |
| DFD-06 Cream | Plasma Concentration of Clobetasol Propionate | Average of 1, 3 and 6 hour | 45.47 pg/mL | Standard Deviation 32.49 |