Clinical trial NCT02245841
Conditions: Dermatomyositis Juvenile Dermatomyositis
Keywords: dermatomyositis Acthar gel
Sponsor: The Cleveland Clinic
Start date: 2015-06-15; Completion date: 2021-07-14
Enrollment: 19 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: 80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks
Interventions: intervention 1: H.P. Acthar Gel
Intervention descriptions: intervention 1: 80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks

Protocol documents:
Prot_SAP_000.pdf: 
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Efficacy and Safety of H.P. Acthar gel for the treatment of refractory cutaneous 
manifestations of dermatomyositis 
 
Principal Investigator:  Anthony Fernandez, MD, PhD 
 
 
Introduction   
 
     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 (1, 2). 
Background and Significance 
     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 patients (3).  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.  Our hypothesis is that H.P. Acthar gel will be safe and effective for treating the cutaneous 
manifestations of dermatomyositis in patients with refractory classic dermatomyositis, juvenile 
dermatomyositis, and amyopathic dermatomyositis. 
 
Study Design 
 
Methods 
   
Prospective, Open-label study 
 
Sample 
 


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Our sample will include approximately 10-15 patients with refractory cutaneous symptoms related to 
either classic dermatomyositis, juvenile dermatomyositis, or amyopathic dermatomyositis.  This sample 
size was chosen to ensure adequate power to detect 50% decreases in the mean total and activity scores of 
the modified CDASI, and 75% decreases in the mean damage scores.  This is not affected by the baseline 
modified CDASI score (though the % change and coefficient of variation will change based on this level).   
Our  inclusion/exclusion criteria are as follows: 
 
Inclusion Criteria: 
• Patients > 18 years old 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) (4-7). 
 
• Patients 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 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). 
 


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• 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. 
 
 
 
 
 
 


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Research Procedures  
 
1)  Upon enrollment patients will undergo a thorough history (including assessing time of diagnosis), 
review of systems, and a complete physical examination. 
2) A detailed examination of the skin and mucous membranes will be performed, noting for 
presence/absence of the following: scalp erythema and atrophy, heliotrope rash, typical erythema and 
atrophy of sun-exposed areas on the neck, upper chest and upper back (shawl sign), erythema +/- scaling 
of the elbows and/or knees (Gottron’s sign), gottron’s papules, periungual erythema, ragged cuticles, 
proximal nailfold capillary loops, palmar scaling and hyperkeratosis (mechanic’s hands), a rash involving 
the hips (holster sign), oral ulcerations, cutaneous ulcerations, purpura. 
3)  Objective cutaneous dermatomyositis scoring by the primary investigator using the modified 
Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) score and Abbreviated 
Cutaneous Assessment Tool (aCAT) will be performed at each visit (8-13). 
4)  Objective general cutaneous disease scoring by the primary investigator using the Physician Global 
Activity for (a) overall skin (b) skin activity (c) skin damage will be performed at each visit (each 
assessed using both VAS-0-10 visual analog scale and Likert scale- 0-4 for each) (9). 
5)  Objective scoring tools to be completed by the patient at each visit will include:  Patient Global 
Assessment (Skin) Score (0-10 visual analog scale), Patient Global (Itch) Score (0-10 visual analog 
scale), and the Dermatology Life Quality Index (validated quality of life assessment) (8-12). 
6) Photographs of all cutaneous lesions will be performed at baseline and at each follow-up visit. 
7) Evaluation for current presence of myositis will be performed using the Manual Muscle Testing 8 
(MMT-8) scoring tool by the primary investigator, as well as with serologic studies below (11, 12). 
8) Completion of the Myositis Disease Activity Assessment Tool (MDAAT) by the primary investigator 
to assess disease activity of extramuscular organ systems (12). 
9) Serologic studies at baseline will include an AM cortisol level, CBC w/ diff, CMP, CK, aldolase, LDH, 
comprehensive myositis panel (ARUP labs), C3, C4, and HbA1c.  The above serologic studies (except for 
the comprehensive myositis panel) will be repeated at the final visit. 


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10) Patients may continue their current immunosuppressive treatment regimens at the time of starting 
H.P. Acthar.  If it is felt that patients should taper off of medications they will require a washout period: 
- corticosteroids- 2weeks  
- methotrexate/azathioprine/mycophenolate/cyclosporine/sirolimus- 4 weeks 
- adalimumab/infliximab/IVIG/chlorambucil/cyclophosphamide- 8 weeks 
- rituximab- 6 months.   
They will be instructed to continue topical medications, moisturizers, and sunscreen based on their current 
practice, which will be recorded at baseline and during subsequent visits. 
11) All patients will receive 80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 
24 weeks (approximately 6 months).  
12) Patients will require follow-up visits in person at 1mo (+/- 5 days), 3mo (+/- 5 days), and 6mo (+/- 
5 days) after initiation of the H.P. Acthar, at which time examinations and clinical scoring tool 
assessments will be repeated.   
13)  If corticosteroids are continued in patients receiving H.P. Acthar gel they will be tapered at the 
primary investigator’s discretion based on clinical evaluation at follow-up appointments. 
14)  H.P. Acthar will be discontinued in any given patient at the primary investigator’s discretion if 
deemed necessary for the patient’s overall health and well-being at any point during the study.  
 
 
Serologic Studies 
 
Baseline 
6mo  
CBC w/ diff 
X 
X 
CMP 
X 
X 
AM cortisol level 
X 
X 
Creatine Kinase 
X 
X 
Aldolase 
X 
X 
LDH 
X 
X 
C3 
X 
X 
C4 
X 
X 
HbA1c 
X 
X 
Comprehensive myositis panel (ARUP labs) 
X 
 
 
Length of above tests is that of a typical phlebotomy blood draw. 
 
 
 
 
 


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Research Protocol Guidelines (continued) 
 
 
 
Clinical Assessments 
 
Baseline 
1 mo +/- 5d 
3mo +/- 5d 
6mo  +/- 5d 
Modified CDASI 
X 
X 
X 
X 
aCAT 
X 
X 
X 
X 
PGA (VAS scoring) 
X 
X 
X 
X 
PGA (Likert scoring) 
X 
X 
X 
X 
Global Patient Score 
(by pt) 
X 
X 
X 
X 
Global Itch Score (by 
pt) 
X 
X 
X 
X 
DLQI 
X 
X 
X 
X 
MMT-8 
X 
X 
X 
X 
MDAAT 
X 
X 
X 
X 
 
Length of each test/procedure: 
Modified CDASI: 5 min 
aCAT:  5-10 min 
PGA (VAS scoring): < 1 minute 
PGA (Likert scoring): < 1 minute 
Global Patient Score: < 1 min 
Global Itch Score: < 1 min  
DLQI: 5 min 
MMT-8: 5 min 
MDAAT: 15-30 min (depending on severity of disease) 
 
**see references above associated with each individual test for details concerning validity and reliability 
 
 
 
Study End Points 
1. Primary end-points: 
     Statistically significant improvement in cutaneous manifestations of dermatomyositis based on 
changes in modified CDASI score, CAT score, and Physican’s Global Assessment (overall, 
activity, damage) scores at end of study vs. baseline. 
 
2. Secondary end-points: 
a) Statistically significant change in MDAAT Score and MMT-8 score 


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b) Statistically significant change in Global Patient Score, Global Itch Score, and/or the Dermatology 
Life Quality Index scores between baseline and 6 months. 
c)  Safety and tolerability of H.P. Acthar gel based on frequency and types of adverse effects. 
d)  median/mean change in glucocorticoid dose from initiation to completion of study. 
e)  median/mean change in dose of systemic steroid-sparing immunosuppressive agents from initiation to 
completion of study. 
f)  median/mean change in HbA1c 
 
Data Analysis 
Access to Data will be limited to the P.I., research coordinator, and research nurse. Approval from the 
IRB to allow access to data will be sought via an IRB amendment application if any additional research 
personnel are added to the study. 
Confidentiality of patients will be protected by assigning numbers to patients and avoiding use of PHI. 
Results of the study will be reported in aggregate and anonymously 
Statistical analyses will be conducted by the section of Biostatistics in the Quantitative Health Sciences 
department at the Cleveland Clinic using the methods described below: 
Statistical Methods 
Patient and disease characteristics will be summarized using means, standard deviations, medians and 
other percentiles of interest for continuous measures and frequencies and percentages for categorical 
factors.  Changes in scoring tool measures from baseline to six months will be calculated and compared 
using paired t-tests.  If necessary, transformations of the data will be performed prior to analysis to meet 
distributional assumptions.   If proper transformations cannot be found, then nonparametric Wilcoxon 


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signed rank tests will be performed.  To assess trends scores over time, linear mixed effect models will be 
fit and estimates of the average change per month will be calculated.  Analysis will be performed using 
SAS software (The SAS Institute; Cary, NC).  A significance level of 0.05 will be assumed for all tests. 
 
Sample Size Considerations 
The primary assessment tool will be the CDASI.  Scores for the modified CDASI range from 0 to 100 for 
activity, 0 to 32 for damage, and 0 to132 for the total score.  In the paper by Yassaee (2010), investigators 
found a mean (SD) activity score of 17.83 (10.14), a mean (SD) damage score of 2.27 (2.73), and a mean 
(SD) total score of 20.10 (10.25).  Given the apparent skewed distributions for these scores, a log-normal 
distribution for the scores was assumed.  In these distributions, a coefficient of variation (CV = SD/Mean) 
of 0.6 appears appropriate for activity and total scores, while a CV of 1.25 was assumed for comparisons 
of total score.  The required sample size for each scale to achieve 80% power to detect 25%, 50%, and 
75% decreases in CDASI scores, based on the assumptions above, and assuming use of two-sided paired 
t-tests on log-transformed values.  These calculations further assume that a small positive correlation 
(r=0.25) between baseline and 6-month scores within person, and use of a 0.05 significance level.  Note 
that since Activity and Total CDASI scores assume the same CV, sample size requirements are identical.  
Under these assumptions, 10 patients are need to detect a 50% decrease in the mean CDASI activity score 
or CDASI total score with 80% power.  This sample size would allow adequate power to detect decreases 
of at least 70% in the mean damage score.  Eight patients would be required to detect a 75% decrease in 
the mean damage score.   
Adverse Events and Data Monitoring Committee(DMC) 
• Patients will be instructed to call immediately with any adverse events.  All adverse events will be 
recorded during the administration of H.P. Acthar.  Any serious adverse events will be reported 
immediately to the appropriate contact person at Questcor, as well as to the IRB in accordance with 
their policy. 
• A DMC will not be used because H.P. Acthar is an approved drug for treatment of 
dermatomyositis. 


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• A DRC is not planned given that Acthar is currently used in clinical medicine to treat multiple 
sclerosis and has a well-known adverse effect profile with low risk of significant adverse 
events. 
• An interim analysis is not planned. 
Consent 
Consent will be obtained in a clinical setting by a member of the study team at the time of planned 
enrollment.  Children under the age of 18 and non-English speaking subjects will not be enrolled in this 
clinical study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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References 
 
1.  Femia AN, Vleugels RA, Callen JP. Cutaneous dermatomyositis: an updated review of treatment 
options and internal associations.  Am J Clin Dermatol. 2013 Aug;14(4):291-313. 
2.  Krathen MS, Fiorentino DF, Werth VP.  Dermatomyositis.  Curr Dir Autoimmun 2008; 10: 313-332. 
3.  Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: 
a retrospective case series. Drug Des Devel Ther 2012;6:133-9. 
4. Bohan A, Peter JB.  Polymyositis and dermatomyositis.  N Engl J Med 1975; 292(7): 344-7. 
5.  Bohan A, Peter JB.  Polymyositis and dermatomyositis.  N Engl J Med 1975; 292(8): 403-7. 
 
6.  Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD.  A systematic review of adult-onset 
clinically amyopathic dermatomyositis (dermatomyositis sine myositis): a missing link within the 
spectrum of the idiopathic inflammatory myopathies.  J Am Acad Dermatol 2006; 54: 597-613. 
 
7.  Euwer RL, Sontheimer RD.  Amyopathic dermatomyositis: a review.  J Invest Dermatol 1993; 100: 
124S-127S. 
8.  Klein RQ, Bangert CA, Costner M, Connolly MK, et al.  Comparison of the reliability and validity of 
outcome instruments for cutaneous dermatomyositis.  Br J Dermatol 2008; 159: 887-894. 
9.  Goreshi R, Okawa J, Rose M, Feng R, et al.  Evaluation of reliability, validity, and responsiveness of 
the CDASI and CAT-BM.  J Invest Dermatol 2012; 132: 1117-1124. 
10.  Carroll CL, Lang W, Snively B, Feldman SR et al.  Development and validation of the 
dermatomyositis skin severity index.  Br J Dermatol 2008; 158: 345-350. 
11.  Rider LG, Werth VP, Huber AM, Alexanderson H et al.  Measures of adult and juvenile 
dermatomyositis, polymyositis, and inclusion body myositis.  Arth Care Res 2011; 63(S11): S118-S157. 
12.  Rider LG, Koziol D, Giannini EH, Jain MS et al.  Validation of manual muscle testing and a subset of 
eight muscles for adult and juvenile idiopathic inflammatory myopathies.  Arth Care and Res 2010; 465-
472. 
13.  Yassaee M, Fiorentino D, Okawa J, Taylor L, Coley AB. Troxel AB, Werth VP.  Modificiation of the 
Cutaneous Dermatomyositis Disease Area and Severity Index, an outcome instrument.  Br J Dermatol 
2010; 162:  669-673.