Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis
Condition: Dermatomyositis, Adult Type
MeSH terms: Dermatomyositis
Intervention: Apremilast 30mg
Intervention description: Patients with refractory cutaneous dermatomyositis will be started on apremilast 30 mg twice a day in addition to a stable dose of their treatment regimen (including steroids and steroid sparing agents).
Intervention MeSH terms: Apremilast
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: dermatomyositis; apremilast; recalcitrant cutaneous disease

Summary:

      With limited treatment options available for dermatomyositis, the investigators hypothesize
      that apremilast, a phosphodiesterase-4 (PDE-4) inhibitor, is a safe and efficacious add-on
      treatment in patients with refractory cutaneous dermatomyositis.

      The study will investigate the efficacy, safety and toxicity of apremilast given at 30 mg
      twice daily to patients with refractory cutaneous dermatomyositis. Clinical response will be
      assessed at 1 and 3 months. Patients will also be evaluated for durability of their response
      for up to 6 months.

      Treatment will be monitored with frequent clinical visits (0, 1, 3 and 6 months) and blood
      tests (CBC, CMP, creatine kinase, aldolase). Treatment will be discontinued at disease
      progression or unacceptable adverse events. Disease progression is defined as 4 points
      increase in the cutaneous dermatomyositis disease area and severity index (CDASI) score,
      worsening of muscle disease by manual muscle testing (MMT-8) score and 5 points increase in
      dermatomyositis life quality index (DLQI).

      5 mm skin biopsies from lesional skin will be performed before treatment with apremilast and
      after 3 months of treatment for gene expression profiling and confirmatory
      immunohistochemical stains.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must understand the risks and the benefits/purpose of the study and provide signed and
             dated informed consent.

          -  Must be 18 years at time of signing the informed consent form.

          -  Willing to participate in all required evaluations and procedures in the study
             including the ability to swallow pills without difficulty.

          -  Patients must have a diagnosis of DM based upon the characteristic cutaneous findings
             proposed by Sontheimer[6] and/or a skin biopsy consistent with DM.

          -  Patients must be candidate for systemic therapy for their DM skin disease defined by
             inadequate response to aggressive sun protection along with the use of potent topical
             corticosteroids and/or immunomodulators.

          -  Patients with a diagnosis of dermatomyositis on steroid-sparing agent and/or systemic
             steroids (maximum dose of prednisone 1mg/Kg) and still having cutaneous disease
             activity of at least 5 on the CDASI scale.

          -  If on immunosuppressive treatments and/or steroids, patients must be on stable doses
             for at least 4 weeks (28 days).

          -  Patients must undergo age appropriate cancer screening.

          -  Females of childbearing potential (FCBP) must have a negative pregnancy test at
             screening (day 0 of the study and every month throughout the study). While on
             investigational product and for at least 28 days after taking the last dose of
             investigational product.

        Exclusion Criteria:

          -  Increasing or changing dose of topical therapy within 14 days of study day 0
             (including but not limited to topical corticosteroids, tacrolimus, pimecrolimus).

          -  Increasing or changing systemic steroids dosing within 28 days of study day 0.

          -  Increasing or changing dosing for concurrent therapy agents within 28 days or 5
             half-lives of the biologic agent, whichever is longer, before study day 0:
             methotrexate, azathioprine, mycophenolate mofetil, hydroxychloroquine, dapsone,
             leflunomide, cyclosporine, biologic agents (anti-TNFs), IVIG, rituximab.

          -  History of any clinically significant (as determined by the investigators) cardiac,
             endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic,
             immunologic, or other major uncontrolled disease.

          -  Any condition, including the presence of laboratory abnormalities, which places the
             patient at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          -  Pregnant or breastfeeding.

          -  Untreated Latent Mycobacterium tuberculosis infection or active tuberculosis infection
             as indicated by a positive Purified Protein Derivative (PPD) skin test or T-spot.

          -  Any condition, including the presence of laboratory abnormalities that places the
             patient at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          -  Patients with acute dermatomyositis onset and rapid progression of muscle disease or
             significant systemic involvement including pulmonary diseases associated with DM.

          -  Prior major surgery or major life-threatening medical illness within 2 weeks.

          -  Inflammatory bowel disease, malabsorption or any other gastrointestinal motility
             disorders that limit the absorption of the study drug.

          -  Active hepatitis B or C infection with detectible viral nucleic acid in the blood or
             known Human Immunodeficiency Virus (HIV) positivity.

          -  Prior history of suicide attempt at any time in the patient's lifetime prior to
             screening or randomization, or major psychiatric illness requiring hospitalization
             within the last 3 years.

          -  Active substance abuse or a history of substance abuse within 6 months prior to
             screening.

          -  Use of any investigational drug within 4 weeks prior to randomization, or 5
             pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).

          -  Prior treatment with apremilast.

          -  Any severe systemic illness requiring IV antibiotics within the two weeks prior to
             initiation of the study drug.

          -  Malignancy or history of malignancy within the past four years, except for:

               -  treated [ie, cured] basal cell or squamous cell in situ skin carcinomas;

               -  treated [ie, cured] cervical intraepithelial neoplasia (CIN) or carcinoma in situ
                  of cervix with no evidence of recurrence within the previous 4 years.