Efficacy and Safety of H.P. Acthar Gel for the Treatment of Refractory Cutaneous Manifestations of Dermatomyositis

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02245841
• Collaborator: Mallinckrodt (Industry)
• Enrollment: 15
• Location: 1
• Arm: 1
• Actual Duration (Months): 73
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dermatomyositis; Juvenile Dermatomyositis	Drug: H.P. Acthar Gel	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of H.P. Acthar Gel for the Treatment of Refractory Cutaneous Manifestations of Dermatomyositis
• Actual Study Start Date: Jun 15, 2015
• Actual Primary Completion Date: Jul 14, 2021
• Actual Study Completion Date: Jul 14, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: H.P Acthar Gel 80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks	Drug: H.P. Acthar Gel; 80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks; Other Names: Acthar Gel

Outcome Measures

Primary Outcome Measures

1. Change from baseline in cutaneous manifestations of dermatomyositis at 1, 3, and 6 months [6 months]

   Statistically significant change between baseline and 1, 3, and 6 months in cutaneous manifestations of dermatomyositis based on modified CDASI (modified Cutaneous Dermatomyositis Disease Area and Severity Index) scores at these timepoints.

2. Change from baseline in cutaneous manifestations of dermatomyositis at 1, 3, and 6 months [6 months]

   Change between baseline and 1, 3, and 6 months in cutaneous manifestations of dermatomyositis based on Physician's Global Assessment scores at these timepoints.

Secondary Outcome Measures

1. Change from baseline in patient assessment of dermatomyositis at 1, 3, and 6 months [6 months]

   Statistically significant change between baseline and 1, 3, and 6 months in patient assessed "Global Patient Score" at these timepoints.

2. Change from baseline in patient assessment of dermatomyositis at 1, 3, and 6 months [6 months]

   Statistically significant change between baseline and 1, 3, and 6 months in patient assessed "Global Itch Score" at these timepoints.

3. Change from baseline in patient assessment of dermatomyositis at 1, 3, and 6 months [6 months]

   Statistically significant change between baseline and 1, 3, and 6 months in patient assessed Dermatology Life Quality Index (DLQI) scores at these timepoints.

Other Outcome Measures

1. Number of patients with adverse effects. [6 months]

   Safety and tolerability of H.P. Acthar gel based on frequency and types of adverse effects.

2. 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

3. Number of patients with change in HbA1c [6 months]

   Median/mean change in HbA1c

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• The Cleveland Clinic
• Mallinckrodt

Investigators

• Principal Investigator: Anthony P Fernandez, MD, PhD, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344-7. Review.
• Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975 Feb 20;292(8):403-7. Review.
• Euwer RL, Sontheimer RD. Amyopathic dermatomyositis: a review. J Invest Dermatol. 1993 Jan;100(1):124S-127S. Review.
• Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD. A systematic review of adult-onset clinically amyopathic dermatomyositis (dermatomyositis siné myositis): a missing link within the spectrum of the idiopathic inflammatory myopathies. J Am Acad Dermatol. 2006 Apr;54(4):597-613. Epub 2006 Jan 23. Review.
• Klein RQ, Bangert CA, Costner M, Connolly MK, Tanikawa A, Okawa J, Rose M, Fakharzadeh SS, Fiorentino D, Lee LA, Sontheimer RD, Taylor L, Troxel AB, Werth VP. Comparison of the reliability and validity of outcome instruments for cutaneous dermatomyositis. Br J Dermatol. 2008 Sep;159(4):887-94. doi: 10.1111/j.1365-2133.2008.08711.x. Epub 2008 Jul 4.
• Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series. Drug Des Devel Ther. 2012;6:133-9. doi: 10.2147/DDDT.S33110. Epub 2012 Jun 11. Erratum in: Drug Des Devel Ther. 2012;6:163.
• Yassaee M, Fiorentino D, Okawa J, Taylor L, Coley C, Troxel AB, Werth VP. Modification of the cutaneous dermatomyositis disease area and severity index, an outcome instrument. Br J Dermatol. 2010 Mar;162(3):669-73. doi: 10.1111/j.1365-2133.2009.09521.x. Epub 2009 Oct 26.

• Responsible Party: Anthony Fernandez, MD, PhD, Md, PhD, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT02245841
• Other Study ID Numbers: 14-1015
• First Posted: Sep 22, 2014
• Last Update Posted: Sep 16, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Anthony Fernandez, MD, PhD, Md, PhD, The Cleveland Clinic: dermatomyositis; Acthar gel
• Additional relevant MeSH terms: Dermatomyositis; Adrenocorticotropic Hormone

Study Results

No Results Posted as of Sep 16, 2021