Recurrent Aphtous StomatitisPhase 3PREMSNCT04227314

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

A Phase 3 study testing Apremilast in people with Recurrent Aphtous Stomatitis, run by University Hospital, Rouen at 21 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

Search all trials

Trial summary

The objective of the study is to assess the superiority of apremilast in comparison with placebo to achieve Complete Remission (CR) of oral ulcers at Week 12, in patients with severe Recurrent aphtous stomatitis resistant or intolerant to colchicine. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Recurrent Aphtous Stomatitis
What is being tested?: Apremilast
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 134 participants
Where: 21 sitesFrance
Study dates: 10 Apr 2022to Dec 2026
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:
- 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

Who cannot join

Patient has any significant medical condition, significant laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Patient has secondary RAS (e.g., celiac disease, Crohn's disease, ulcerative colitis, relapsing polychondritis, PFAPFA, AIDS…).
Depression and suicidal ideation
Co-medication with a cytochrome P450 3A4 (CYP3A4) enzyme inducer ( especially, rifampicin and most anti-epileptic drugs (e.g. carbamazepine, phenytoin)
Severely underweight patient (BMI < 18.5 kg/m2)
Patient cannot be followed regularly.

Show all 23Show fewer

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),
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...)
Patient is currently enrolled in any other therapeutic trial.
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.
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.
Patient with positive blood test for HIV.
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.
Patient has received a live vaccine within 3 months of baseline or plans to do so during study.
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.
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).
Patient has used biologic therapy including anti TNF within 5 pharmacokinetic half-lives.
Prior treatment with apremilast, or participation in a clinical study, involving apremilast.
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.
Galactose intolerance, lactase deficiency or glucose/galactose malabsorption
Patient is deemed unreliable or for any reason not able to comply with the protocol
Patient with alcohol dependency
Male patient intending to conceive a child with his partner

Trial locations and contacts

21 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Pascal JOLY, Pr contact

+3323288 ext. 8265

pascal.joly@chu-rouen.fr

Julien BLOT contact

+3323288 ext. 8265

julien.blot@chu-rouen.fr

City, postcode or hospital

Sites recruiting now only

21 sites in 1 country

France21 sites, 21 recruiting

Chu Amiens
Amiens, 80054
Guillaume Chaby, Dr, 03 22 45 58 41, Guillaume.chaby@chu-amiens.fr
Guillaume Chaby, Dr
Not yet recruiting
Ap-Hp Avicenne
Bobigny, 93000
Christelle Leroux, Dr, 01 49 81 25 12, christelle.leroux@aphp.fr
Christelle Leroux, Dr
Recruiting
Chu Bordeaux
Bordeaux, 33076
Marie Beylot Barry, Pr, 05 57 82 25 00, marie.beylot-barry@chu-bordeaux.fr
Marie Beylot Barry, Pr
Recruiting
Chru Brest
Brest, 29200
Laurent Misery, Pr, 02 98 22 33 15, laurent.misery@chu-brest.fr
Laurent Misery, Pr
Recruiting
Ch Creteil
Créteil, 94010
Pham Thuy-Giao, Dr, 01 57 02 32 15, Pham.Do@chicreteil.fr
Pham Thuy-Giao, Dr
Recruiting
Ch Le Mans
Le Mans, 72037
Nathalie Beneton, Dr, nbeneton@ch-lemans.fr
Nathalie Beneton, Dr
Recruiting
Chu Lille
Lille, 59000
Selma Azib, Dr, 03.20.44.41.91, Selma.MEFTAH@CHRU-LILLE.FR
Selma Azib, Dr
Recruiting
Hcl Hopital Edouard Herriot
Lyon, 69003
Pauline Bouschon, Dr, pauline.bouschon@chu-lyon.fr
Pauline Bouschon, Dr
Recruiting
Ap-Hm La Timone
Marseille, 13385
Marie-Aleth Richard, Pr, 04 91 38 79 91, marie-aleth.richard@ap-hm.fr
Marie-Aleth Richard, Pr
Recruiting
Chu Montpellier
Montpellier, 34295
Céline Girard, Dr, 04 67 33 69 06, celine-girard@chu-montpellier.fr
Céline Girard, Dr
Recruiting
Chu Nantes
Nantes, 44000
Gaelle Quereux, Pr, 02 40 08 31 44, gaelle.quereux@chu-nantes.fr
Gaelle Quereux, Pr
Recruiting
CHU NICE
Nice, 06000
Margaux Garnier, Dr, 04.92.03.66.67, Garnier.m@chu-nice.fr
Margaux Garnier, Dr
Recruiting
Ap-Hp Pitie Salpetriere
Paris, 75013
Céline Bernardeschi, Dr, celine.bernardeschi@aphp.fr
Céline Bernardeschi, Dr
Recruiting
Ap-Hp Pitie-Salpetriere
Paris, 75013
Juliette Rochefort, Dr, 01 42 17 84 16, juliette.rochefort@aphp.fr
Juliette Rochefort, Dr
Not yet recruiting
Hopital Cochin
Paris, 75014
Camille Isnard, 06 09 36 62 46, camille.isnard@aphp.fr"
Camille Isnard
Recruiting
Chu Reims
Reims, 51092
Manuelle Viguier, Pr, 03 10 73 66 76, mviguier@chu-reims.fr
Manuelle Viguier, Pr
Recruiting
Chu Rouen
Rouen, 76031
Pascal Joly, Pr, 02 32 88 68 41, pascal.joly@chu-rouen.fr
Pascal Joly, Pr
Recruiting
Ch Saint-Brieux
Saint-Brieuc, 22023
Gilles Safa, Dr, 02 96 01 71 23, gilles.safa@armorsante.bzh
Gilles Safa, Dr
Not yet recruiting
Chu Saint-Etienne
Saint-Etienne, 42055
Jean-Luc Perrot, Dr, 04 77 82 83 33, j.luc.perrot@chu-st-etienne.fr
Jean-Luc Perrot, Dr
Not yet recruiting
Chu Toulouse
Toulouse, 31059
Vincent Sibaud, Dr, 06 31 53 39 49, Sibaud.Vincent@iuct-oncopole.fr
Vincent Sibaud, Dr
Recruiting
Chru Tours
Tours, 37170
Mahtab Samimi, Pr, 02 47 47 47 47, mahtab.samimi@univ-tours.fr
Mahtab Samimi, Pr
Recruiting

Other trials in France

About this study

Conditions: Recurrent Aphtous Stomatitis
Being tested: Apremilast, Placebo oral tablet

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ApremilastDrug
Apremilast: 30 mg twice daily during a 12 week double blind placebo controlled period, then 30 mg twice daily during an additional 12 week active treatment period
Placebo oral tabletDrug
Placebo: 30 mg twice daily during the initial 12 week double blind placebo controlled period,

Study groups in NCT04227314
Study group	Role	What they receive
Apremilast	Experimental	apremilast: 30 mg twice daily during a 12 week double blind placebo controlled period, then 30 mg twice daily during an additional 12 week active treatment period Receives: Drug: Apremilast
Placebo	Placebo comparator	Placebo: 30 mg twice daily during the initial 12 week double blind placebo controlled period Receives: Drug: Placebo oral tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

Presence of oral ulcer during clinical examination
Presence or absence of oral ulcer
Measured: Week 12
Presence of oral ulcer during clinical examination
Presence or absence of oral ulcer
Measured: Week 14

Secondary outcomes (5)

Number of oral ulcer during clinical examination
Mean cumulative number of oral ulcers at the Week 12 evaluation
Measured: Week 12
Number of oral ulcer during clinical examination
Mean cumulative number of oral ulcers at the Week 14 evaluation
Measured: Week 14
Difference from baseline in quality of life
quality of life will be evaluated using SF36
Measured: Week 14
Occurrence since baseline of severe and adverse events
Measured: Week 14
Occurrence since baseline of non-severe adverse events
Measured: Week 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Apr 2022Dec 2026

First posted13 Jan 2020
Study start10 Apr 2022
Primary completionDec 2026 (estimated)
Study completionDec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Recurrent Aphtous StomatitisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 134 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04227314
Sponsor's protocol ID: 2019/0411/HP
Acronym: PREMS
Status last verified: Feb 2026
First submitted: 13 Dec 2019
Last updated: 17 Feb 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Double Blind Controlled Trial Comparing the Safety and Efficacy of Apremilast Versus Placebo in Severe Forms of Recurrent Aphthous Stomatitis
ClinicalTrials.gov ID: NCT04227314
Acronym / sponsor ID: PREMS / 2019/0411/HP
Conditions: Recurrent Aphtous Stomatitis
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 134 participants (estimated)
Lead sponsor: University Hospital, RouenUniversity, hospital or other
Study start: 10 Apr 2022 (actual)
Primary completion: Dec 2026 (estimated)
Study completion: Dec 2026 (estimated)
First posted: 13 Jan 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Apremilast	Experimental	Drug: Apremilastapremilast: 30 mg twice daily during a 12 week double blind placebo controlled period, then 30 mg twice daily during an additional 12 week active treatment period
Placebo	Placebo comparator	Drug: Placebo oral tabletPlacebo: 30 mg twice daily during the initial 12 week double blind placebo controlled period

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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:
- 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

Key exclusion criteria (23 listed)

Patient has any significant medical condition, significant laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Patient has secondary RAS (e.g., celiac disease, Crohn's disease, ulcerative colitis, relapsing polychondritis, PFAPFA, AIDS…).
Depression and suicidal ideation
Co-medication with a cytochrome P450 3A4 (CYP3A4) enzyme inducer ( especially, rifampicin and most anti-epileptic drugs (e.g. carbamazepine, phenytoin)
Severely underweight patient (BMI < 18.5 kg/m2)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ApremilastApremilast: 30 mg twice daily during a 12 week double blind placebo controlled period, then 30 mg twice daily during an additional 12 week active treatment period	Drug	Apremilast
Placebo oral tabletPlacebo: 30 mg twice daily during the initial 12 week double blind placebo controlled period,	Drug	Placebo

Primary outcome

Presence of oral ulcer during clinical examination
Time frame: Week 12
Presence or absence of oral ulcer
Presence of oral ulcer during clinical examination
Time frame: Week 14
Presence or absence of oral ulcer

5 secondary outcomes

Number of oral ulcer during clinical examination
Time frame: Week 12
Number of oral ulcer during clinical examination
Time frame: Week 14
Difference from baseline in quality of life
Time frame: Week 14
Occurrence since baseline of severe and adverse events
Time frame: Week 14
Occurrence since baseline of non-severe adverse events
Time frame: Week 14

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Pascal JOLY, Pr contact

+3323288 ext. 8265

pascal.joly@chu-rouen.fr

Julien BLOT contact

+3323288 ext. 8265

julien.blot@chu-rouen.fr

Pascal JOLY, Pr principal investigator

University Hospital, Rouen

21 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Apremilast in people with Recurrent Aphtous Stomatitis, run by University Hospital, Rouen at 21 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Pascal JOLY, Pr (+3323288 ext. 8265, pascal.joly@chu-rouen.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Presence of oral ulcer during clinical examination (time frame: Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04227314.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.