APREMILAST for Recurrent aphthous stomatitis

Inclusion criteria

• {"criterion_text":"- 1.\tMale 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.i) At least one large / giant oral ulcer (≥ 1cm in diameter) confirmed by the investigator during the 3 months month preceding inclusion and/or, ii) Multiple simultaneous oral ulcers (≥4), including herpetiform ulcers confirmed by the investigator during the 3 months preceding inclusion and/or, iii) Continuous evolution of oral ulcers, some lesions healing, as newly appearing oral ulcers develop within the 3 months before inclusion and/or, iv) Ulcers occurring at least 7 days each month during the previous 3 months (15) and/or v) Major pain related to oral ulcers interfering with eating, speaking, or swallowing\n- 2.\tPatient having read and understood the information letter and signed the Informed Consent Form\n- 3.\tFor women: a.\tWomen of childbearing potential : i.\tEffective contraception according to CTFG contraception recommendations (V1.1 21/09/2020) since at least 4 weeks before randomization and during treatment, And; ii.\tNegative blood pregnancy test; b.\tWomen surgically sterile (absence of ovaries and/or uterus); c.\tPostmenopausal women (non-medically induced amenorrhea for at least 12 months prior to the inclusion visit). Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Barrier methods must always be supplemented with the use of a spermicide.\n- 4.\tPatient able to comply with the study protocol, in the investigator’s judgment\n- 5.\tPatient affiliated with, or beneficiary of a social security (health insurance) category"}

Exclusion criteria

• {"criterion_text":"- 1.\tHistory of clinically significant or uncontrolled disease (as determined by the investigator), which places the subject at unacceptable risk if he/she were to participate in the study.\n- 10.\tHypersensitivity of the active substance(s) or to any of the excipients of racecadotril\n- 11.\tPatient is currently enrolled in any other therapeutic trial\n- 12.\tOther than RAS, subject has any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal (defined by creatinine clearance <30 mL / min estimated by Cockroft-Gault equation), hematologic, immunologic disease, or other major disease that is currently uncontrolled in the opinion of the investigator\n- 13.\tMalignancy 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.\n- 14.\tPatients with positive blood test for HIV.\n- 15.\tAny severe 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.\n- 16.\tPatient 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 and use an effective contraception.\n- 17.\tPatient 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)\n- 18.\tPatient has used biologic therapy, including anti-TNF, within 5 pharmacokinetic half-lives of the administrated product.\n- 19.\tPrior treatment with apremilast, or participation in a clinical study, involving apremilast.\n- 2.\tPatient has secondary RAS (e.g., celiac disease, Crohn’s disease, ulcerative colitis, relapsing polychondritis, PFAPFA, AIDS…).\n- 20.\tGalactose intolerance, lactase deficiency or glucose/galactose malabsorption\n- 21.\tPatient is deemed unreliable or for any reason not able to comply with the protocol\n- 22.\tPatient with alcohol dependency\n- 23.\tPersons referred to in articles L1121-5 to L1121-8 of the CSP (pregnant or breastfeeding (lactating) woman, deprived of liberty by administrative or judicial decision or placed under judicial protection (guardianship or supervision)\n- 3.\tDepression and suicidal ideation, in particular prior history of suicide attempt at any time in the subject’s lifetime prior to signing the informed consent, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.\n- 4.\tCo-medication with a cytochrome P450 3A4 (CYP3A4) enzyme inducer (especially, rifampicin and most anti-epileptic drugs (e.g. carbamazepine, phenytoin)\n- 5.\tPatient severely underweight patient (BMI < 16 kg/m2)\n- 6.\tPatient cannot be followed regularly\n- 7.\tPatient 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),\n- 8.\tPatient has any medical condition that requires systemic treatment which may confound the ability to interpret data from the study (ie, lupus erythematosus, rheumatoid arthritis...)\n- 9.\tHypersensitivity of the active substance(s) or to any of the excipients of OTEZLA and placebo"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint will be sustained complete response (CR) (i.e., no oral ulcer at both the Week 12 and Week 14 and Week 16 evaluations), assessed by a blind evaluator (so that the evaluator will not be aware of any digestive complaints from the patient, that may be frequent with apremilast)","definition_or_measurement_approach":"Sustained complete response defined as no oral ulcer at Week 12 and Week 14 and Week 16 evaluations; assessment performed by a blinded evaluator (evaluator unaware of patient's digestive complaints)."}

France

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

23-02-2026

Processing Time Days

538

Number Of Sites

22

Number Of Participants

134

Primary sponsor

Full Name

Centre Hospitalier Universitaire Rouen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France