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

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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