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

NCT04227314 | Recruiting Phase 3

• 1 other identifier: 2019/0411/HP
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 21

Brief 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.

Conditions

Recurrent Aphtous Stomatitis

Outcome Measures

Primary Outcomes (2)

• Presence of oral ulcer during clinical examination

  Presence or absence of oral ulcer

  Week 12

• Presence of oral ulcer during clinical examination

  Presence or absence of oral ulcer

  Week 14

Secondary Outcomes (5)

• Number of oral ulcer during clinical examination

  Week 12

• Number of oral ulcer during clinical examination

  Week 14

• Difference from baseline in quality of life

  Week 14

• Occurrence since baseline of severe and adverse events

  Week 14

• Occurrence since baseline of non-severe adverse events

  Week 14

Study Arms (2)

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

Drug: Apremilast

Placebo

PLACEBO COMPARATOR

Placebo: 30 mg twice daily during the initial 12 week double blind placebo controlled period

Drug: Placebo oral tablet

Interventions

Apremilast DRUG

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

Apremilast

Placebo oral tablet DRUG

Placebo: 30 mg twice daily during the initial 12 week double blind placebo controlled period,

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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:
• \. 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (21)

Chu Amiens

Amiens, 80054, France

NOT YET RECRUITING

Ap-Hp Avicenne

Bobigny, 93000, France

RECRUITING

Chu Bordeaux

Bordeaux, 33076, France

RECRUITING

Chru Brest

Brest, 29200, France

RECRUITING

Ch Creteil

Créteil, 94010, France

RECRUITING

Ch Le Mans

Le Mans, 72037, France

RECRUITING

Chu Lille

Lille, 59000, France

RECRUITING

Hcl Hopital Edouard Herriot

Lyon, 69003, France

RECRUITING

Ap-Hm La Timone

Marseille, 13385, France

RECRUITING

Chu Montpellier

Montpellier, 34295, France

RECRUITING

Chu Nantes

Nantes, 44000, France

RECRUITING

CHU NICE

Nice, 06000, France

RECRUITING

Ap-Hp Pitie Salpetriere

Paris, 75013, France

RECRUITING

Ap-Hp Pitie-Salpetriere

Paris, 75013, France

NOT YET RECRUITING

Hopital Cochin

Paris, 75014, France

RECRUITING

Chu Reims

Reims, 51092, France

RECRUITING

Chu Rouen

Rouen, 76031, France

RECRUITING

Ch Saint-Brieux

Saint-Brieuc, 22023, France

NOT YET RECRUITING

Chu Saint-Etienne

Saint-Etienne, 42055, France

NOT YET RECRUITING

Chu Toulouse

Toulouse, 31059, France

RECRUITING

Chru Tours

Tours, 37170, France

RECRUITING

MeSH Terms

Interventions

apremilast

Study Officials

• Pascal JOLY, Pr

  University Hospital, Rouen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pascal JOLY, Pr

CONTACT

+3323288; pascal.joly@chu-rouen.fr

Julien BLOT

CONTACT

+3323288; julien.blot@chu-rouen.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double blind study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2019
• First Posted: January 13, 2020
• Study Start: April 10, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (21)