Dermatomyositis, Juvenile Dermatomyositis
Conditions
Keywords
dermatomyositis, Acthar gel
Brief summary
This study will assess the safety and efficacy of H.P. Acthar gel for treating the cutaneous manifestations in patients with refractory classic dermatomyositis, juvenile dermatomyositis, and amyopathic dermatomyositis. Our hypothesis is that H.P. Acthar gel will be both safe and effective for such patients.
Detailed description
Adult and juvenile dermatomyositis (DM) are systemic immune-mediated inflammatory diseases most commonly affecting the skin and musculoskeletal system. Amyopathic dermatomyositis is a subtype of dermatomyositis that affects only the skin and lacks the characteristic muscle involvement. Treatment of these conditions, in particular the cutaneous manifestations, is challenging and currently no universally effective single treatment exists. Many patients have cutaneous manifestations that are refractory to numerous medications. H.P. Acthar gel (adrenocorticotropic hormone gel) received FDA approval for treatment of a variety of diseases, including dermatomyositis, in 1952. Despite this there is a paucity of clinical data concerning the efficacy of H.P. Acthar gel for treating dermatomyositis. Recently a small, retrospective case series describing significant improvement in both cutaneous and musculoskeletal symptoms in 5 patients with refractory dermatomyositis treated with H.P. Acthar gel was reported and has resulted in renewed interest in use of this medication in dermatomyositis patient (reference below). The proposed efficacy of H.P. Acthar gel has been attributed to its unique ability to induce production of endogenous cortisol, corticosterone, aldosterone, and to bind melanocortin receptors on lymphocytes and other cells to modulate immunologic responses.
Interventions
DRUGH.P. Acthar Gel
80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks
Sponsors
Mallinckrodt
The Cleveland Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be 18 years of age or older with refractory cutaneous symptoms related to either classic dermatomyositis (CD), juvenile dermatomyositis (JD), or amyopathic dermatomyositis(AD). Diagnosis will be based on either Bohan and Peter criteria (CD and JD) or Sontheimer's criteria (AD) * Must have had a skin biopsy with histologic features consistent with dermatomyositis and current cutaneous manifestations consistent with dermatomyositis. * Although not mandatory, patients with evidence of current or previous active myositis will be eligible for enrollment. Patients will be considered to have refractory disease if cutaneous manifestations exist despite treatment with steroids and at least one steroid-sparing systemic treatment commonly found to be useful in patients with dermatomyositis. These may include azathioprine, cyclosporine, mycophenolate mofetil, IVIG, methotrexate, cyclophosphamide, chlorambucil, sirolimus, adalimumab, infliximab and rituximab. * Use of topical medications and sunscreen currently and in past will be noted but not weighed for assessment of refractory cutaneous disease.
Exclusion criteria
* Patients with dermatomyositis who have minimal-to-no active cutaneous features (focal involvement with less than 1% total body surface area involved or minimal modified CDASI activity score). * Patients whose cutaneous findings are not consistent with dermatomyositis and/or have previous biopsy results suggestive of an alternative diagnosis * Patients with inflammatory myositis other than dermatomyositis, such as polymyositis or inclusion body myositis. * Patients with malignancy-associated dermatomyositis * Patients with clear features of an overlap myositis * Patients younger than 18 years old * Patients with acutely active or chronic infections. * Patients with uncontrolled diabetes, hypertension, cardiovascular, hepatic, or renal disease * Pregnant or lactating females. * Patients with any medical condition that is felt by the primary investigator to place the patient at unreasonable risk for adverse effects during treatment with H.P. Acthar. * Hypersensitivity to H.P. Acthar, any of its components (allergy to pig-derived proteins) * Patients with osteoporosis * Patients who have had surgery within 8 weeks of screening * Patients with a history of or current gastric ulcers * Patients taking daily doses of systemic corticosteroids greater than the equivalent of 40mg prednisone.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cutaneous Dermatomyositis at 6 Months | 6 months | Change between baseline at 6 months in modified CDASI-A (Cutaneous Dermatomyositis Disease Area and Severity Index) scores at these timepoints. The CDASI-A score ranges from 0 to 100 with higher scores reflecting more severe disease activity. |
| Change in Physician's Global Assessment (PGA) Visual Acuity Score From Baseline to 6 Months | 6 months | Change from baseline to 6 months in Physician's Global Assessment (PGA) visual acuity score. Scores range from 0-10 with Higher scores reflecting severe disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Patient Global Itch Score of Dermatomyositis at 6 Months | 6 months | Change between baseline and 6 months in patient assessed Global Itch Score at these timepoints. The Global Itch score ranges from 0 to 10 with higher scores reflect more severe itching. |
| Change From Baseline in Patient Assessment of Dermatomyositis at 6 Months. | 6 months | Change between baseline and 6 months in patient assessed Global Skin Score at these timepoints. The Global Skin Score ranges from 0 to 10 with lower 0 representing worst sign condition imaginable and 10 representing perfect health. |
| Change From Baseline in Patient Assessment of DLQI Dermatomyositis at 6 Months | 6 months | Change between baseline and 6 months in patient assessed Dermatology Life Quality Index (DLQI) scores at these timepoints. The DLQI ranges from 0 to 30 with higher scores implying more significant impact on quality of life. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Change in Dose of Systemic Corticosteroids and/or Steroid-sparing Immunosuppressive Agents | 6 months | Median/mean change in dose of systemic corticosteroids and/or steroid-sparing immunosuppressive agents from initiation to completion of study |
| Number of Patients With Change in HbA1c | 6 months | Median/mean change in HbA1c |
| Number of Patients With Adverse Effects. | 6 months | Safety and tolerability of H.P. Acthar gel based on frequency and types of adverse effects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| H.P Acthar Gel 80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | H.P Acthar Gel | — |
|---|---|---|
| Age, Continuous | 56 years | — |
| Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI-A) | 19 units on a scale | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 19 participants | — |
| Sex: Female, Male Female | 14 Participants | — |
| Sex: Female, Male Male | 5 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 11 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
Primary
Change From Baseline in Cutaneous Dermatomyositis at 6 Months
Change between baseline at 6 months in modified CDASI-A (Cutaneous Dermatomyositis Disease Area and Severity Index) scores at these timepoints. The CDASI-A score ranges from 0 to 100 with higher scores reflecting more severe disease activity.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| H.P Acthar Gel | Change From Baseline in Cutaneous Dermatomyositis at 6 Months | -9 units on a scale |
Comparison: Analysis performed was two-sided Wilcoxon signed rank test. Median differences with interquartile range are reported in outcome measure data.p-value: <0.001Wilcoxon signed rank test
Primary
Change in Physician's Global Assessment (PGA) Visual Acuity Score From Baseline to 6 Months
Change from baseline to 6 months in Physician's Global Assessment (PGA) visual acuity score. Scores range from 0-10 with Higher scores reflecting severe disease activity.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| H.P Acthar Gel | Change in Physician's Global Assessment (PGA) Visual Acuity Score From Baseline to 6 Months | -1.9 units on a scale |
Comparison: Analysis performed was two-sided Wilcoxon signed rank test. Median differences with interquartile range are reported in outcome measure data.p-value: <0.001Wilcoxon signed rank test
Secondary
Change From Baseline in Patient Assessment of Dermatomyositis at 6 Months.
Change between baseline and 6 months in patient assessed Global Skin Score at these timepoints. The Global Skin Score ranges from 0 to 10 with lower 0 representing worst sign condition imaginable and 10 representing perfect health.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| H.P Acthar Gel | Change From Baseline in Patient Assessment of Dermatomyositis at 6 Months. | 2 units on a scale |
Comparison: Analysis performed was two-sided Wilcoxon signed rank test. Median differences with interquartile range are reported in outcome measure data.p-value: 0.002Wilcoxon signed rank test
Secondary
Change From Baseline in Patient Assessment of DLQI Dermatomyositis at 6 Months
Change between baseline and 6 months in patient assessed Dermatology Life Quality Index (DLQI) scores at these timepoints. The DLQI ranges from 0 to 30 with higher scores implying more significant impact on quality of life.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| H.P Acthar Gel | Change From Baseline in Patient Assessment of DLQI Dermatomyositis at 6 Months | -5 units on a scale |
Comparison: Analysis performed was two-sided Wilcoxon signed rank test. Median differences with interquartile range are reported in outcome measure data.p-value: <0.001Wilcoxon signed rank test
Secondary
Change From Baseline in Patient Global Itch Score of Dermatomyositis at 6 Months
Change between baseline and 6 months in patient assessed Global Itch Score at these timepoints. The Global Itch score ranges from 0 to 10 with higher scores reflect more severe itching.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| H.P Acthar Gel | Change From Baseline in Patient Global Itch Score of Dermatomyositis at 6 Months | -1 units on a scale |
Comparison: Analysis performed was two-sided Wilcoxon signed rank test. Median differences with interquartile range are reported in outcome measure data.p-value: 0.05Wilcoxon signed rank test
Other Pre-specified
Number of Patients With Adverse Effects.
Safety and tolerability of H.P. Acthar gel based on frequency and types of adverse effects.
Time frame: 6 months
Other Pre-specified
Number of Patients With Change in Dose of Systemic Corticosteroids and/or Steroid-sparing Immunosuppressive Agents
Median/mean change in dose of systemic corticosteroids and/or steroid-sparing immunosuppressive agents from initiation to completion of study
Time frame: 6 months
Other Pre-specified
Number of Patients With Change in HbA1c
Median/mean change in HbA1c
Time frame: 6 months