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Randomized double blind controlled trial comparing the safety and efficacy of apremilast versus placebo in severe forms of recurrent aphthous stomatitis - PREMS - 2019/0411/HP
EU CTIS ID: 2024-514659-13-00
What this study is testing
The primary objective of this study is to assess the superiority of apremilast in comparison with placebo to achieve sustained Complete Remission (CR) of oral ulcers, in patients with severe RAS resistant or intolerant to colchicine at Week 12 and Week 14 and Week 16.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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.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
- 2. Patient having read and understood the information letter and signed the Informed Consent Form
- 3. For women: a. Women of childbearing potential : i. Effective contraception according to CTFG contraception recommendations (V1.1 21/09/2020) since at least 4 weeks before randomization and during treatment, And; ii. Negative blood pregnancy test; b. Women surgically sterile (absence of ovaries and/or uterus); c. Postmenopausal 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.
- 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 likely can't join if
- 1. History 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.
- 10. Hypersensitivity of the active substance(s) or to any of the excipients of racecadotril
- 11. Patient is currently enrolled in any other therapeutic trial
- 12. Other 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
- 13. 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.
- 14. Patients with positive blood test for HIV.
See the full eligibility criteria
Who can 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.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
- 2. Patient having read and understood the information letter and signed the Informed Consent Form
- 3. For women: a. Women of childbearing potential : i. Effective contraception according to CTFG contraception recommendations (V1.1 21/09/2020) since at least 4 weeks before randomization and during treatment, And; ii. Negative blood pregnancy test; b. Women surgically sterile (absence of ovaries and/or uterus); c. Postmenopausal 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.
- 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
What rules you out
- 1. History 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.
- 10. Hypersensitivity of the active substance(s) or to any of the excipients of racecadotril
- 11. Patient is currently enrolled in any other therapeutic trial
- 12. Other 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
- 13. 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.
- 14. Patients with positive blood test for HIV.
- 15. Any 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.
- 16. Patient 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.
- 17. 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)
- 18. Patient has used biologic therapy, including anti-TNF, within 5 pharmacokinetic half-lives of the administrated product.
- 19. Prior treatment with apremilast, or participation in a clinical study, involving apremilast.
- 2. Patient has secondary RAS (e.g., celiac disease, Crohn’s disease, ulcerative colitis, relapsing polychondritis, PFAPFA, AIDS…).
- 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. Persons 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)
- 3. Depression 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.
- 4. Co-medication with a cytochrome P450 3A4 (CYP3A4) enzyme inducer (especially, rifampicin and most anti-epileptic drugs (e.g. carbamazepine, phenytoin)
- 5. Patient severely underweight patient (BMI < 16 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. Hypersensitivity of the active substance(s) or to any of the excipients of OTEZLA and placebo
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.