Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis

• Status: Completed
• Trial end date: 2021-04-07
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tulane University
• Treatments: Apremilast; Thalidomide

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.