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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)

Primary Purpose

Recurrent Aphtous Stomatitis

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Apremilast
Placebo oral tablet
Sponsored by
University Hospital, Rouen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Aphtous Stomatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Apremilast

    Placebo

    Arm 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

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

    Outcomes

    Primary Outcome Measures

    Presence of oral ulcer during clinical examination
    Presence or absence of oral ulcer
    Presence of oral ulcer during clinical examination
    Presence or absence of oral ulcer

    Secondary Outcome Measures

    Number of oral ulcer during clinical examination
    Mean cumulative number of oral ulcers at the Week 12 evaluation
    Number of oral ulcer during clinical examination
    Mean cumulative number of oral ulcers at the Week 14 evaluation
    Difference from baseline in quality of life
    quality of life will be evaluated using SF36
    Occurrence since baseline of severe and adverse events
    Occurrence since baseline of non-severe adverse events

    Full Information

    First Posted
    December 13, 2019
    Last Updated
    November 19, 2021
    Sponsor
    University Hospital, Rouen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04227314
    Brief Title
    Randomized Double Blind Controlled Trial Comparing the Safety and Efficacy of Apremilast Versus Placebo in Severe Forms of Recurrent Aphthous Stomatitis
    Acronym
    PREMS
    Official Title
    Randomized Double Blind Controlled Trial Comparing the Safety and Efficacy of Apremilast Versus Placebo in Severe Forms of Recurrent Aphthous Stomatitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 2022 (Anticipated)
    Primary Completion Date
    June 2027 (Anticipated)
    Study Completion Date
    June 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University Hospital, Rouen

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Recurrent Aphtous Stomatitis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Masking Description
    double blind study
    Allocation
    Randomized
    Enrollment
    134 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Apremilast
    Arm Type
    Experimental
    Arm 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
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo: 30 mg twice daily during the initial 12 week double blind placebo controlled period
    Intervention Type
    Drug
    Intervention Name(s)
    Apremilast
    Intervention 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
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo oral tablet
    Intervention Description
    Placebo: 30 mg twice daily during the initial 12 week double blind placebo controlled period,
    Primary Outcome Measure Information:
    Title
    Presence of oral ulcer during clinical examination
    Description
    Presence or absence of oral ulcer
    Time Frame
    Week 12
    Title
    Presence of oral ulcer during clinical examination
    Description
    Presence or absence of oral ulcer
    Time Frame
    Week 14
    Secondary Outcome Measure Information:
    Title
    Number of oral ulcer during clinical examination
    Description
    Mean cumulative number of oral ulcers at the Week 12 evaluation
    Time Frame
    Week 12
    Title
    Number of oral ulcer during clinical examination
    Description
    Mean cumulative number of oral ulcers at the Week 14 evaluation
    Time Frame
    Week 14
    Title
    Difference from baseline in quality of life
    Description
    quality of life will be evaluated using SF36
    Time Frame
    Week 14
    Title
    Occurrence since baseline of severe and adverse events
    Time Frame
    Week 14
    Title
    Occurrence since baseline of non-severe adverse events
    Time Frame
    Week 14

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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: 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. 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). Patient has used biologic therapy including anti TNF within 5 pharmacokinetic half-lives. Prior treatment with apremilast, or participation in a clinical study, involving apremilast. 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. Galactose intolerance, lactase deficiency or glucose/galactose malabsorption Patient is deemed unreliable or for any reason not able to comply with the protocol Patient with alcohol dependency Male patient intending to conceive a child with his partner
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Pascal JOLY, Pr
    Phone
    +3323288
    Ext
    8265
    Email
    pascal.joly@chu-rouen.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Julien BLOT
    Phone
    +3323288
    Ext
    8265
    Email
    julien.blot@chu-rouen.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Pascal JOLY, Pr
    Organizational Affiliation
    Rouen University Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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