Apremilast for RAS
Primary Purpose
Recurrent Aphthous Stomatitis
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Apremilast 30mg
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Aphthous Stomatitis
Eligibility Criteria
Inclusion Criteria
- Male and female subjects between 18 and 70 years of age
- Oral ulcers that occurred at least monthly in the 6 month period prior to enrollment
- Had at least 2 oral ulcers in the 4 weeks prior to enrollment at baseline
- At least 3 oral ulcers during an ulcer flare
- 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.
- 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
- Patients are able and willing to provide written informed consent after the nature of the study is fully explained.
- No evidence of systemic disease
Exclusion Criteria
- Prior use of apremilast.
- Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
- 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.
- Pregnant women or breast-feeding mothers.
- Systemic or opportunistic fungal infection.
- 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.
- History of positive test for, or any clinical suspicion of, human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency.
- History of depression.
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.
- 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.
- 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.
- 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.
- Active substance abuse or a history of substance abuse within 6 months prior to screening.
- Presence of any of the following vitamin deficiencies - B1, B2, B6, B12, vitamin C, zinc, folate, iron.
- Celiac disease.
- Inflammatory Bowel Disease.
- Genital aphthous ulcers.
- Behçet's disease.
- History of positive patch test for allergic contact stomatitis.
- Positive anti-endomysial or anti-gliadin antibodies.
- A diagnosis of uveitis (current or previous).
- Erythema nodosum-like lesions (current or previous).
- An established diagnosis of a systemic disease (SLE, Reiter's, Sweet's and MAGIC syndrome).
Sites / Locations
- Mayo Clinic in Florida
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm
Arm Description
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)
Outcomes
Primary Outcome Measures
Duration of RAS Lesions
The total length of time (duration) subjects experienced RAS lesions. Measured in weeks
Change in Number of RAS Lesions
Number of participants with fewer oral ulcers at Week 24 compared to Baseline
Duration of the Remission Period Between Ulcer Episodes
The length of time of remission of RAS lesions experienced by the subjects. As measured in months.
Secondary Outcome Measures
Adverse Events
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Discontinuation of Study Participants
Number of subjects who prematurely discontinue treatment with apremilast due to any adverse event.
Change in Visual Analog Scale Pain Score (VAS) From Baseline to 16 Weeks and Baseline to 24 Weeks.
The Visual Analog Scale (VAS) for Pain is a validated tool used to measure pain. A 100mm horizontal line anchored by "no pain" (score of 0) and "pain as bad as it could be" (score of 100).
Full Information
NCT ID
NCT03690544
First Posted
September 4, 2018
Last Updated
June 20, 2022
Sponsor
Mayo Clinic
Collaborators
Celgene
1. Study Identification
Unique Protocol Identification Number
NCT03690544
Brief Title
Apremilast for RAS
Official Title
A Pilot Study Evaluating the Efficacy of Apremilast in the Treatment of Subjects With Severe Recurrent Aphthous Stomatitis (RAS)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
October 12, 2018 (Actual)
Primary Completion Date
July 14, 2021 (Actual)
Study Completion Date
July 14, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Celgene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Determination of treatment efficacy and safety of Apremilast in patients with RAS
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Aphthous Stomatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Apremilast 30mg orally twice daily for 16 weeks
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
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.
Primary Outcome Measure Information:
Title
Duration of RAS Lesions
Description
The total length of time (duration) subjects experienced RAS lesions. Measured in weeks
Time Frame
24 weeks
Title
Change in Number of RAS Lesions
Description
Number of participants with fewer oral ulcers at Week 24 compared to Baseline
Time Frame
baseline, 24 weeks
Title
Duration of the Remission Period Between Ulcer Episodes
Description
The length of time of remission of RAS lesions experienced by the subjects. As measured in months.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Adverse Events
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
24 weeks
Title
Discontinuation of Study Participants
Description
Number of subjects who prematurely discontinue treatment with apremilast due to any adverse event.
Time Frame
24 weeks
Title
Change in Visual Analog Scale Pain Score (VAS) From Baseline to 16 Weeks and Baseline to 24 Weeks.
Description
The Visual Analog Scale (VAS) for Pain is a validated tool used to measure pain. A 100mm horizontal line anchored by "no pain" (score of 0) and "pain as bad as it could be" (score of 100).
Time Frame
baseline, 16 weeks, 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Male and female subjects between 18 and 70 years of age
Oral ulcers that occurred at least monthly in the 6 month period prior to enrollment
Had at least 2 oral ulcers in the 4 weeks prior to enrollment at baseline
At least 3 oral ulcers during an ulcer flare
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.
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
Patients are able and willing to provide written informed consent after the nature of the study is fully explained.
No evidence of systemic disease
Exclusion Criteria
Prior use of apremilast.
Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
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.
Pregnant women or breast-feeding mothers.
Systemic or opportunistic fungal infection.
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.
History of positive test for, or any clinical suspicion of, human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency.
History of depression.
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.
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.
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.
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.
Active substance abuse or a history of substance abuse within 6 months prior to screening.
Presence of any of the following vitamin deficiencies - B1, B2, B6, B12, vitamin C, zinc, folate, iron.
Celiac disease.
Inflammatory Bowel Disease.
Genital aphthous ulcers.
Behçet's disease.
History of positive patch test for allergic contact stomatitis.
Positive anti-endomysial or anti-gliadin antibodies.
A diagnosis of uveitis (current or previous).
Erythema nodosum-like lesions (current or previous).
An established diagnosis of a systemic disease (SLE, Reiter's, Sweet's and MAGIC syndrome).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alison J Bruce
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Apremilast for RAS
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