Acthar in Treatment of Refractory Dermatomyositis and Polymyositis

NCT01906372 | Completed Phase 2 Results

• 1 other identifier: PRO13050507
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research study is to evaluate the effectiveness of the study drug, ACTH Gel in people diagnosed with dermatomyositis a disease that causes muscle weakness and is associated with a rash (DM) or polymyositis (PM) a disease that causes muscle weakness without a rash. The study doctors want to evaluate whether ACTH Gel will improve the symptoms of this disease. This drug is approved by the Food and Drug Administration (FDA) for dermatomyositis (DM) and polymyositis (PM). ACTH gel has been an FDA-approved treatment for myositis since 1952, and in 2010 the FDA retained PM and DM as diseases approved for ACTH gel use.

Conditions

Dermatomyositis; Polymyositis

Keywords

dermatomyositis; polymyositis

Outcome Measures

Primary Outcomes (1)

• Specific Aim 1: Number of Subjects Meeting IMACS Preliminary Definition of Improvement (DOI).

  3 of any of the 6 core set measures (CSM) improved by ≥ 20%, with no more than 2 CSM worsening by ≥25% (worsening measure cannot include the MMT). The DOI should be met at least once on any of the 6 follow up visits and maintained until week 24. Subjects not meeting DOI during the trial are treatment failures.

  Primary end point: IMACS preliminary definition of improvement (DOI)

Secondary Outcomes (1)

• Steroid-sparing Effect of H.P. Acthar Gel in Refractory Adult PM and DM Patients.

  Steroid sparing effect and safety and tolerability at 24 weeks compared to baseline

Study Arms (1)

Acthar Gel

EXPERIMENTAL

Acthar Gel (Adrenocorticotropic Hormone Gel)in refractory PM and DM patients using an open label design for 6 months. We will enroll 10 active and refractory PM/DM patients over a 15 month period, followed by 6 months of additional follow-up for each subject. Study subjects will self-administer subcutaneously H.P. Acthar Gel 80 units (1 ml) twice a week for a period of six months. Outcome measures were not evaluated on subjects who did not reach the 8 week time point in the trial.

Drug: Adrenocorticotropic Hormone Gel

Interventions

Adrenocorticotropic Hormone Gel DRUG

H.P. Acthar Gel 80 units will be self-administered subcutaneously twice weekly by the subject for a period of 6 months.

Also known as: H.P. Acthar Gel

Acthar Gel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Definite or probable polymyositis (PM) or dermatomyositis (DM) by Bohan and Peter criteria.
• PM patients must either possess a myositis-associated autoantibody or undergo adjudication for confirmation of the PM diagnosis by consensus of two experts to ensure non-PM patients are not enrolled. This step is necessary since there are well-known mimics of PM.
• Age ≥ 18 years.
• Active myositis as defined by baseline Manual Muscle Testing (MMT-8) no greater than 125/150 and at least 2 additional CSM meeting the criteria stipulated below:
• Patient global with a minimum value of 2.0 cm on a 10 cm visual analog scale(VAS)
• Physician global with a minimum value of 2.0 cm on a 10 cm VAS scale
• Health Assessment Questionnaire (HAQ) disability index with a minimum value of 0.25
• Elevation of at least one of the muscle enzymes \[which includes creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)\] at a minimum level of 1.3 x the upper limit of normal.
• Global extramuscular disease activity score with a minimum value of 1.0 cm on a 10 cm VAS scale \[this measure is the physician's composite evaluation and is based on assessments of activity scores on the constitutional, cutaneous, skeletal, gastrointestinal, pulmonary and cardiac scales of the Myositis Disease Activity Assessment Tool (MDAAT)\].
• To ensure that we can enroll active DM patients with a severe rash who may not meet the MMT-8 criterion noted above, we propose additional enrollment criteria such that the International Myositis Assessment and Clinical Studies (IMACS) definition of improvement (DOI) can potentially be met:
• Cutaneous VAS score on MDAAT \> 3 cm on a 10 cm VAS scale, and
• At least 3 of the above 5 (a through e under 4.) criteria.
• Refractory myositis is defined by active disease despite an adequate glucocorticoid trial (\> 2 months of usual glucocorticoid therapy or intolerance to such therapy) and/or ≥ 1 conventional immunosuppressive agent (e.g. methotrexate, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil, IVIG, anti-TNF or rituximab) for a reasonable dose and duration (\> 3 months or intolerance to therapy). It is recommended to enroll refractory patients failing (or intolerant to) both glucocorticoids and at least 1 conventional immunosuppressive agent.
• If the enrolling physician is planning to continue current immunosuppressive agents or glucocorticoids as concomitant therapy with Acthar gel during the trial, then patient must be on a stable glucocorticoid and/or immunosuppressive dose 2 weeks prior to visit 1. The patient should have been on that immunosuppressive medication for at least 8 weeks (and at least 4 weeks for glucocorticoids) prior to visit 1.
• If the enrolling physician is planning to discontinue current immunosuppressive agent or glucocorticoids, then following wash out period is required prior to visit 1.

You may not qualify if:

• Hypersensitivity to Acthar
• Severe cardiac or pulmonary involvement
• Severe muscle damage defined as a baseline global muscle damage score on the MDI (Myositis Damage Index) of ≥ 5 cm on a 10 cm VAS.
• Patients with malignancy within 3 years of screening (except basal cell cancer or squamous cell cancer of skin).
• Uncontrolled diabetes, hepatic or renal disease.
• Ongoing active or chronic infections.
• Pregnant or lactating females.
• For any medical or physical or socio-psychological reasons that PI feels would not allow the subject to complete the study.

Sponsors & Collaborators

• Rohit Aggarwal, MD: lead
• Mallinckrodt: collaborator

Study Sites (2)

North Shore LIJ Medical Center

Great Neck, New York, 11021, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Related Publications (10)

• Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev. 2004 Mar;56(1):1-29. doi: 10.1124/pr.56.1.1.

  PMID: 15001661 BACKGROUND

• Catania A, Lonati C, Sordi A, Carlin A, Leonardi P, Gatti S. The melanocortin system in control of inflammation. ScientificWorldJournal. 2010 Sep 14;10:1840-53. doi: 10.1100/tsw.2010.173.

  PMID: 20852827 BACKGROUND

• Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996 Mar;97(3):375-9.

  PMID: 8604274 BACKGROUND

• Bomback AS, Tumlin JA, Baranski J, Bourdeau JE, Besarab A, Appel AS, Radhakrishnan J, Appel GB. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011 Mar 14;5:147-53. doi: 10.2147/DDDT.S17521.

  PMID: 21448451 BACKGROUND

• Simsarian JP, Saunders C, Smith DM. Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: a prospective, randomized, open-label pilot trial. Drug Des Devel Ther. 2011;5:381-9. doi: 10.2147/DDDT.S19331. Epub 2011 Jul 11.

  PMID: 21792296 BACKGROUND

• 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.

  PMID: 22787386 BACKGROUND

• Rider LG, Giannini EH, Brunner HI, Ruperto N, James-Newton L, Reed AM, Lachenbruch PA, Miller FW; International Myositis Assessment and Clinical Studies Group. International consensus on preliminary definitions of improvement in adult and juvenile myositis. Arthritis Rheum. 2004 Jul;50(7):2281-90. doi: 10.1002/art.20349.

  PMID: 15248228 BACKGROUND

• Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, Barohn RJ, Feldman BM, Harris-Love MO, Koontz DC, Fertig N, Kelley SS, Pryber SL, Miller FW, Rockette HE; RIM Study Group. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013 Feb;65(2):314-24. doi: 10.1002/art.37754.

  PMID: 23124935 BACKGROUND

• Fernandez AP, Gallop J, Polly S, Khanna U. Efficacy and safety of repository corticotropin injection for refractory cutaneous dermatomyositis: a prospective, open-label study. Rheumatology (Oxford). 2024 Dec 1;63(12):3370-3379. doi: 10.1093/rheumatology/kead595.

  PMID: 37941470 DERIVED

• Aggarwal R, Marder G, Koontz DC, Nandkumar P, Qi Z, Oddis CV. Efficacy and safety of adrenocorticotropic hormone gel in refractory dermatomyositis and polymyositis. Ann Rheum Dis. 2018 May;77(5):720-727. doi: 10.1136/annrheumdis-2017-212047. Epub 2017 Dec 13.

  PMID: 29237618 DERIVED

MeSH Terms

Conditions

Dermatomyositis; Polymyositis

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Limitations and Caveats

Small pilot open label single arm trial. Larger double blinded placebo controlled randomized trials are required.

Results Point of Contact

• Title: Rohit Aggarwal, MD
• Organization: University of Pittsburgh, Division of Rheumatology

aggarwalr@upmc.edu

412-647-2840

Study Officials

• Rohit Aggarwal, MD

  University of Pittsburgh, Division of Rheumatology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 5, 2013
• First Posted: July 24, 2013
• Study Start: September 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: May 1, 2016
• Last Updated: September 1, 2017
• Results First Posted: August 2, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)