Brief Title
Randomized Double Blind Controlled Trial Comparing the Safety and Efficacy of Apremilast Versus Placebo in Severe Forms of Recurrent Aphthous Stomatitis
Official Title
Randomized Double Blind Controlled Trial Comparing the Safety and Efficacy of Apremilast Versus Placebo in Severe Forms of Recurrent Aphthous Stomatitis
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Presence of oral ulcer during clinical examination
Secondary Outcome
Number of oral ulcer during clinical examination
Condition
Recurrent Aphtous Stomatitis
Intervention
Apremilast
Study Arms / Comparison Groups
Apremilast
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
134
Start Date
January 2022
Completion Date
June 2027
Primary Completion Date
June 2027
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Pascal JOLY, Pr, +3323288, [email protected]
Administrative Informations
NCT ID
NCT04227314
Organization ID
2019/0411/HP
Responsible Party
Sponsor
Study Sponsor
University Hospital, Rouen
Study Sponsor
Pascal JOLY, Pr, Principal Investigator, Rouen University Hospital
Verification Date
November 2021