Apremilast for RAS
Condition: Recurrent Aphthous Stomatitis
MeSH terms: Stomatitis; Stomatitis, Aphthous
Intervention: Apremilast 30mg
Intervention description: Apremilast is an oral small-molecule inhibitor of phosphodiesterase (PDE) 4 that works intracellularly to modulate a network of pro-inflammatory and anti-inflammatory mediators. PDE 4 is a cyclic adenosine monophosphate (cAMP)-specific PDE and the dominant PDE in inflammatory cells. PDE4 inhibition elevates intracellular cAMP levels, which in turn down-regulates the inflammatory response by modulating the expression of TNF-alfa, IL-23, IL-17 and other inflammatory cytokines. Cyclic AMP also modulates levels of anti-inflammatory cytokines such as IL-10. Apremilast has immunomodulatory activity and, therefore, has the potential to be effective in the treatment of RAS.
Intervention MeSH terms: Apremilast
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Apremilast 30mg orally twice daily for 16 weeks
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      Determination of treatment efficacy and safety of Apremilast in patients with RAS
    

Eligibility criteria:

        Inclusion Criteria

          1. Male and female subjects between 18 and 70 years of age

          2. Oral ulcers that occurred at least monthly in the 6 month period prior to enrollment

          3. Had at least 2 oral ulcers in the 4 weeks prior to enrollment at baseline

          4. At least 3 oral ulcers during an ulcer flare

          5. Patients must be candidates for systemic therapy for the treatment of oral ulcers,
             those that are considered unsuitable for topical therapy alone based on severity of
             disease, or whose oral ulcers cannot be adequately controlled with topical therapy.

          6. Female premenopausal subjects must use one of the approved contraceptive options while
             taking apremilast and for at least 28 days after administration of the last dose of
             apremilast

          7. Patients are able and willing to provide written informed consent after the nature of
             the study is fully explained.

          8. No evidence of systemic disease

        Exclusion Criteria

          1. Prior use of apremilast.

          2. Use of any investigational drug within 4 weeks prior to randomization, or 5
             pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).

          3. Having received concomitant immune modulating therapy 12 weeks prior to enrollment,
             systemic steroids 6 weeks prior to enrollment or topical steroids within 4 weeks prior
             to enrollment.

          4. Pregnant women or breast-feeding mothers.

          5. Systemic or opportunistic fungal infection.

          6. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
             or other infections (tuberculosis and atypical mycobacterial disease, hepatitis B and
             C and herpes zoster, histoplasmosis, coccidiomycosis) or any major episode of
             infection requiring hospitalization or treatment with IV or oral antibiotics within 4
             weeks of the screening phase.

          7. History of positive test for, or any clinical suspicion of, human immunodeficiency
             virus (HIV), or congenital or acquired immunodeficiency.

          8. History of depression.

          9. Malignancy or history of malignancy, except for:

             a - treated (ie, cured) basal cell or squamous cell in situ skin carcinomas; b -
             treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of
             cervix with no evidence of recurrence within the previous 5 years.

         10. Other than disease under study, any clinically significant (as determined by the
             Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic,
             renal, hematologic, immunologic disease, or other major disease that is currently
             uncontrolled.

         11. Any condition, including the presence of laboratory abnormalities, which would place
             the subject at unacceptable risk if he/she were to participate in the study.

         12. Prior history of suicide attempt at any time in the subject's life time prior to
             screening or randomization, or major psychiatric illness requiring hospitalization
             within the last 3 years.

         13. Active substance abuse or a history of substance abuse within 6 months prior to
             screening.

         14. Presence of any of the following vitamin deficiencies - B1, B2, B6, B12, vitamin C,
             zinc, folate, iron.

         15. Celiac disease.

         16. Inflammatory Bowel Disease.

         17. Genital aphthous ulcers.

         18. Behçet's disease.

         19. History of positive patch test for allergic contact stomatitis.

         20. Positive anti-endomysial or anti-gliadin antibodies.

         21. A diagnosis of uveitis (current or previous).

         22. Erythema nodosum-like lesions (current or previous).

         23. An established diagnosis of a systemic disease (SLE, Reiter's, Sweet's and MAGIC
             syndrome).