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Apremilast versus placebo for severe recurrent mouth ulcers

Randomized Double Blind Controlled Trial Comparing the Safety and Efficacy of Apremilast Versus Placebo in Severe Forms of Recurrent Aphthous Stomatitis

Phase 3 Interventional University Hospital, Rouen · NCT04227314

This tests whether the oral medicine apremilast can completely heal severe recurring mouth ulcers by 12 weeks in adults who do not respond to or cannot take colchicine.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment134 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity Hospital, Rouen Academic / other
Locations21 sites (Amiens and 20 other locations)
Trial IDNCT04227314 on ClinicalTrials.gov

What this trial studies

This Phase 3 randomized, double-blind, placebo-controlled trial compares oral apremilast to matching placebo in adults with severe primary recurrent aphthous stomatitis who are resistant or intolerant to colchicine. Eligible patients must have at least one oral ulcer at baseline and meet prespecified severity criteria such as giant ulcers, multiple simultaneous ulcers, continuous new lesions, frequent monthly ulcers, or major pain interfering with eating or speaking. Participants are randomized to receive apremilast or placebo and are followed through Week 12 with complete remission of oral ulcers at Week 12 as the primary endpoint. The trial is conducted at multiple French university hospitals with CHU Rouen as the lead site.

Who should consider this trial

Good fit: Adults (≥18 years) with severe primary recurrent aphthous stomatitis who have failed or are intolerant to colchicine and who have at least one oral ulcer at the time of enrollment are the intended participants.

Not a fit: People with mild or infrequent aphthous ulcers, those who respond well to colchicine, or individuals with contraindications to apremilast are unlikely to gain benefit from this trial.

Why it matters

Potential benefit: If successful, apremilast could provide an effective oral option to induce complete healing of severe, colchicine-resistant mouth ulcers and reduce pain and eating or speaking difficulties.

How similar studies have performed: Apremilast has shown benefit for oral ulcers in Behçet's disease and is effective in other inflammatory disorders, but evidence specifically for primary recurrent aphthous stomatitis is limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 1\. Male or female patients aged ≥18 years old with severe primary RAS resistant to colchicine prescribed at a dose of 1mg/day or more for at least 3 months, or intolerant to colchicine

Severity of primary oral aphtous ulcer is defined by the presence of at least one of the following criteria:

i) - At least one giant oral ulcer (≥ 1cm in diameter) confirmed by the investigator during the month preceding inclusion and/or, ii) - Multiple simultaneous oral ulcers ( ≥4), including herpetiform ulcers confirmed by the investigator during the month preceding inclusion and/or, iii) - Continuous evolution of oral ulcers, some lesions healing, as newly appearing oral ulcers develop within the month before inclusion and/or, iv) - Oral ulcers occurring at least 7 days each month during the previous 3 months and/or v) - Major pain related to oral ulcers interfering with eating, speaking, or swallowing

\- In all cases, patients must have at least one oral ulcer on the date of inclusion

2\. Patient having read and understood the information letter and signed the Informed Consent Form 3. For women who are not postmenopausal and who do not plan on having children anymore: agreement to remain abstinent or use two adequate methods of contraception 4. Patient able to comply with the study protocol, in the investigator's judgment 5. Patient affiliated with, or beneficiary of a social security (health insurance) category

Exclusion Criteria:

1. Patient has any significant medical condition, significant laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Patient has secondary RAS (e.g., celiac disease, Crohn's disease, ulcerative colitis, relapsing polychondritis, PFAPFA, AIDS…).
3. Depression and suicidal ideation
4. Co-medication with a cytochrome P450 3A4 (CYP3A4) enzyme inducer ( especially, rifampicin and most anti-epileptic drugs (e.g. carbamazepine, phenytoin)
5. Severely underweight patient (BMI \< 18.5 kg/m2)
6. Patient cannot be followed regularly.
7. Patient has any other inflammatory oral disease, which confounds the ability to interpret data from the study (ie, lichen planus, auto immune bullous diseases with oral involvement),
8. Patient has any medical condition that requires systemic treatment which may confound the ability to interpret data from the study (ie, lupus erythematosus, rheumatoid arthritis...)
9. Patient is currently enrolled in any other therapeutic trial.
10. Other than RAS, subject has 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. Malignancy or history of malignancy or myeloproliferative or lymphoproliferative disease within the past 5 years, except for treated (ie, cured) basal cell or squamous cell carcinomas, in situ cervix carcinoma, or any situation in which the oncologist in charge of the patient considers that oncologic risk allows the use of apremilast.
12. Patient with positive blood test for HIV.
13. Any bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed and the infection cured, at least 4 weeks prior to Screening and no new or recurrent infections prior to the Baseline Visit.
14. Patient has received a live vaccine within 3 months of baseline or plans to do so during study.
15. Patient is a pregnant or breastfeeding (lactating) woman or intending to become pregnant during the study; Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative result from a serum pregnancy test within 1 week prior to randomization.
16. Patient has used systemic therapy which may potentially be effective in RAS within four weeks prior to randomization (including, but not limited to corticosteroids, azathioprine, levamisole, thalidomide).
17. Patient has used biologic therapy including anti TNF within 5 pharmacokinetic half-lives.
18. Prior treatment with apremilast, or participation in a clinical study, involving apremilast.
19. Patient has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
20. Galactose intolerance, lactase deficiency or glucose/galactose malabsorption
21. Patient is deemed unreliable or for any reason not able to comply with the protocol
22. Patient with alcohol dependency
23. Male patient intending to conceive a child with his partner

Where this trial is running

Amiens and 20 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Recurrent Aphtous Stomatitis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.