Apremilast for RAS

• ClinicalTrials.gov Identifier: NCT03690544
• Recruitment Status: Active, not recruiting
• First Posted: October 1, 2018
• Last Update Posted: December 17, 2020
• Sponsor: Mayo Clinic
• Collaborator: Celgene
• Information provided by (Responsible Party): Alison J. Bruce, Mayo Clinic

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Recurrent Aphthous Stomatitis	Drug: Apremilast 30mg	Early Phase 1

Detailed Description:

The study will be a pilot study using apremilast 30mg orally twice daily, for treatment of RAS in males and females between 18 and 70 years old.

Subjects will be recruited from the clinical practice of the Department of Dermatology or Division of Rheumatology at Mayo Clinic Florida. Fifteen males and females with RAS will be enrolled.

The study will consist of 3 phases: a screening phase, a 16 week treatment phase and an 8 week posttreatment observational follow-up phase.

The screening phase will consist of: obtaining informed consent, demographic information, medical history, inclusion and exclusion criteria, prior and concomitant medication use, adverse events; collecting vital signs and weight; performing complete physical examination and limited physical examination; obtaining hematology, serum chemistry, urinalysis, pregnancy test and providing contraception education.

During the 16-week treatment phase, all subjects receive apremilast.

All subjects who complete the active treatment phase are to enter the 8-week posttreatment observational follow-up phase.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Apremilast 30mg orally twice daily for 16 weeks
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study Evaluating the Efficacy of Apremilast in the Treatment of Subjects With Severe Recurrent Aphthous Stomatitis (RAS)
• Actual Study Start Date: October 12, 2018
• Estimated Primary Completion Date: March 1, 2021
• Estimated Study Completion Date: March 1, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Single Arm; Apremilast 30mg orally twice daily for 16 weeks, sixteen weeks on active study. Post treatment follow-up period of 8 weeks, in the Treatment of Subjects with Severe Recurrent Aphthous Stomatitis (RAS)

Drug: Apremilast 30mg; 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.

Outcome Measures

Primary Outcome Measures :

1. Improvement in duration of RAS lesions [ Time Frame: up to 24 weeks ]
   Improvement in the duration of oral ulcers will be used to factor the improvement of RAS lesions.
2. Percentage change in number of RAS lesions [ Time Frame: up to 24 weeks ]
   The percentage change in the number of oral ulcers will be used to factor the improvement of RAS lesions.
3. Improvement in duration of the remission period between ulcer episodes [ Time Frame: up to 24 weeks ]
   Improvement in duration of the remission period between ulcer episodes will be used to factor the improvement of RAS lesions.

Secondary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 24 weeks ]
   Type, frequency, severity and relationship of the adverse events to apremilast will be assessed and reported.
2. Discontinuation of study participants [ Time Frame: 24 weeks ]
   Number of sbjects who prematurely discontinue treatment with apremilast due to any adverse event.
3. Frequency of clinically significant changes in vital signs and/or laboratory findings [ Time Frame: 24 weeks ]
   The frequency of clinically significant changes in vital signs and/or laboratory findings will be measured through a complete physical examination using physiological parameters, as well as hematology and serum chemistry.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

United States, Florida

Mayo Clinic in Florida

Jacksonville, Florida, United States, 32224

Sponsors and Collaborators

Mayo Clinic

Celgene

Investigators

• Principal Investigator: Alison J Bruce; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Alison J. Bruce, Principle Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03690544
• Other Study ID Numbers: 18-002914
• First Posted: October 1, 2018
• Last Update Posted: December 17, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Stomatitis; Stomatitis, Aphthous; Mouth Diseases; Stomatognathic Diseases; Apremilast; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents