Trial Outcomes & Findings for Apremilast for RAS (NCT NCT03690544)

Results Overview

The total length of time (duration) subjects experienced RAS lesions. Measured in weeks

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

15 participants

Primary outcome timeframe

24 weeks

Results posted on

2022-07-14

Participant Flow

Participant milestones

Participant milestones
Measure	Single Arm Subjects received 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) 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.
Overall Study STARTED	15
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Apremilast for RAS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single Arm n=15 Participants Subjects received 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) 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.
Age, Continuous	56 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Race/Ethnicity, Customized White	14 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

The total length of time (duration) subjects experienced RAS lesions. Measured in weeks

Outcome measures

Outcome measures
Measure	Single Arm n=15 Participants Subjects received 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) 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.
Duration of RAS Lesions	1.57 weeks Standard Deviation 0.68

PRIMARY outcome

Timeframe: baseline, 24 weeks

Number of participants with fewer oral ulcers at Week 24 compared to Baseline

Outcome measures

Outcome measures
Measure	Single Arm n=15 Participants Subjects received 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) 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.
Change in Number of RAS Lesions	11 participants

PRIMARY outcome

Timeframe: 24 weeks

The length of time of remission of RAS lesions experienced by the subjects. As measured in months.

Outcome measures

Outcome measures
Measure	Single Arm n=15 Participants Subjects received 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) 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.
Duration of the Remission Period Between Ulcer Episodes	2.00 months Standard Deviation 0.85

SECONDARY outcome

Timeframe: 24 weeks

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Outcome measures

Outcome measures
Measure	Single Arm n=15 Participants Subjects received 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) 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.
Adverse Events	11 Participants

SECONDARY outcome

Timeframe: 24 weeks

Number of subjects who prematurely discontinue treatment with apremilast due to any adverse event.

Outcome measures

Outcome measures
Measure	Single Arm n=15 Participants Subjects received 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) 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.
Discontinuation of Study Participants	3 Participants

SECONDARY outcome

Timeframe: baseline, 16 weeks, 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).

Outcome measures

Outcome measures
Measure	Single Arm n=15 Participants Subjects received 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) 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.
Change in Visual Analog Scale Pain Score (VAS) From Baseline to 16 Weeks and Baseline to 24 Weeks. baseline to 16 weeks	-4 units on a scale Standard Deviation 3.0
Change in Visual Analog Scale Pain Score (VAS) From Baseline to 16 Weeks and Baseline to 24 Weeks. baseline to 24 weeks	-2 units on a scale Standard Deviation 4.0

Adverse Events

Single Arm

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Single Arm n=15 participants at risk Subjects received 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) 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.
General disorders Nausea	60.0% 9/15 • Adverse events were collected from baseline to end of study, approximately 24 weeks
Gastrointestinal disorders Diarrhea	33.3% 5/15 • Adverse events were collected from baseline to end of study, approximately 24 weeks

Additional Information

Alison J. Bruce, M.B., Ch.B.

Mayo Clinic

Phone: 904-953-6402

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place