Acthar in Treatment of Refractory Dermatomyositis and Polymyositis

Open Label Proof of Concept Study to Evaluate Efficacy and Safety of Adrenocorticotropic Hormone Gel in Refractory Dermatomyositis or Polymyositis

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.

Despite its FDA approval there is very limited data on its clinical effectiveness in PM and DM. There was a recent study published in the peer-review journal Drug Design, Development and Therapy on a retrospective case series evaluating Acthar in the treatment of PM and DM. Acthar was administered to five patients who had previously failed multiple steroid and immunosuppressant treatment regimens. The patients received injections of Acthar over the course of 12 weeks or more. Improvement in PM and DM symptoms related to disease exacerbations was seen in all five patients. Symptom improvements included increased muscle strength, resolution of disease-related skin manifestations and improvements in the ability to perform tasks associated with daily living. All of these patients tolerated the treatment well with no significant side effects reported. The paper, "Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series," was authored by Dr. Todd Levine, M.D., Co-Director of the Neurophysiology Department at Banner Good Samaritan Medical Center, Assistant Professor at the University of Arizona in Neurology, and Member of Phoenix Neurological Associates.

H.P. Acthar® Gel, or Acthar, is a prescription medication containing the hormone adrenocorticotropin (hormone produced and secreted by the anterior pituitary gland), also known as ACTH. H.P. Acthar Gel is a highly purified preparation of adrenocorticotropic hormone (ACTH) in a gel that is designed to provide extended release of the ACTH following injection. Acthar was originally approved by the FDA in 1952. It is approved for use in 19 different conditions including dermatomyositis and polymyositis.

Acthar is designed to provide a prolonged release of the medication after it is injected. Acthar is not a steroid; it works by helping your body produce its own natural steroid hormones, such as cortisol, corticosterone, and aldosterone. Acthar is an injection that is given intramuscularly (into the muscle). Subjects enrolled in the study will be asked to self administer Acthar two times per week. Subjects will be provided training by the principal investigator on how to perform the self injections.

Inclusion Criteria:

• 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:

  1. Patient global with a minimum value of 2.0 cm on a 10 cm visual analog scale(VAS)
  2. Physician global with a minimum value of 2.0 cm on a 10 cm VAS scale
  3. Health Assessment Questionnaire (HAQ) disability index with a minimum value of 0.25
  4. 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.
  5. 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:

  1. Cutaneous VAS score on MDAAT > 3 cm on a 10 cm VAS scale, and
  2. 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.

• If previous concomitant medications were discontinued, the following wash out periods are required prior to Visit 1

• Methotrexate -4 weeks

• Other IS agent (e.g. azathioprine, cyclosporine, tacrolimus, leflunomide, mycophenolate mofetil) - 4 weeks

• IVIg or cyclophosphamide - 2 months

• rituximab -6 months

• infliximab or adalimumab -8 weeks

• glucocorticoids - 2 weeks

• etanercept -2 weeks

• anakinra -1 week

Exclusion Criteria:

• Juvenile DM or PM, myositis in overlap with another connective tissue disease, cancer associated myositis, inclusion body myositis, or any other non immune-mediated myopathy.
• 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.