<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03836885</url>
  </required_header>
  <id_info>
    <org_study_id>049-2018</org_study_id>
    <nct_id>NCT03836885</nct_id>
  </id_info>
  <brief_title>Apremilast - Oral Lichen Planus Trial</brief_title>
  <acronym>APOLP</acronym>
  <official_title>The APOLP Trial: A Single-Center, Randomized, 16 Weeks, Explanatory, Parallel-Group, Superiority, Blinded, Placebo-Controlled, Clinical Trial of Apremilast Use in Oral Lichen Planus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sunnybrook Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sunnybrook Health Sciences Centre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Apremilast for the management of oral lichen planus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Oral lichen planus (OLP) affects approximately 1.27% of the general population. Inflammatory&#xD;
      responses constitute a major component of OLP pathogenesis where targeted therapies play an&#xD;
      important role in managing this condition. Apremilast is a new well-tolerated and relatively&#xD;
      safe anti-inflammatory therapy that has been approved for managing psoriasis and psoriatic&#xD;
      arthritis. Given its safer profile, Apremilast may ameliorate inflammatory responses in&#xD;
      clinically active OLP without the experience of serious adverse events associated with other&#xD;
      systemic immunosuppressive therapies used to treat OLP. The plan is to conduct a&#xD;
      single-center, explanatory, randomized, 16 weeks, parallel group, superiority, blinded,&#xD;
      placebo-controlled, clinical trial.&#xD;
&#xD;
      The main objective is treatment success assessment. Other objectives include exploring the&#xD;
      efficacy of Apremilast in clinically active OLP adult patients considered for systemic&#xD;
      treatment and failed topical corticosteroid therapy. It is hypothesized that Apremilast will&#xD;
      induce more treatment success as compared to placebo in patients who failed the standard&#xD;
      treatment of topical corticosteroids.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study was terminated due to delay in enrollment.&#xD;
  </why_stopped>
  <start_date type="Actual">November 21, 2019</start_date>
  <completion_date type="Actual">April 22, 2020</completion_date>
  <primary_completion_date type="Actual">April 22, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessing treatment success defined as Physician Global Assessment (PhGA) of 0 or 1</measure>
    <time_frame>Baseline to 16 weeks</time_frame>
    <description>The primary outcome will be assessing treatment success with Apremilast as compared to placebo defined as Physician Global Assessment (PhGA) of 0 or 1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Achieving complete remission defined as achieving a score of 0 on PhGA scale</measure>
    <time_frame>12 weeks and 16 weeks</time_frame>
    <description>Complete remission is defined as achieving a score of 0 on PhGA scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physician Global Assessment (PhGA)</measure>
    <time_frame>Baseline to 16 weeks</time_frame>
    <description>Physician Global Assessment (PhGA) grading score from 0 to 4. Score of 0 is clear, score of 1 is almost clear, score of 2 is mild disease, score of 3 is moderate disease, and a score of 4 is severe disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Assessment (PtA)</measure>
    <time_frame>Baseline to 16 weeks</time_frame>
    <description>Patient Assessment (PtA) grading score from 0 to 4. Score of 0 is clear, score of 1 is almost clear, score of 2 is mild disease, score of 3 is moderate disease, and a score of 4 is severe disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Achieving partial response</measure>
    <time_frame>Baseline to 12 weeks</time_frame>
    <description>Percentage of patients who achieve partial response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual Analogue Scale (VAS)</measure>
    <time_frame>Baseline to 16 weeks</time_frame>
    <description>Patient assessment of pain score from 0 to 10. VAS is a scale demonstrated by a 10 cm horizontal line marked from 0-10 with the left end marked as no symptoms (0) and the right end marked as worst symptoms (10).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral Health Impact Profile (OHIP-14) Scale</measure>
    <time_frame>Baseline to 16 weeks</time_frame>
    <description>Patient assessment of overall disease impact on quality of life is a self-filled validated scale that focuses on seven domains: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability and handicap. Participants will be asked to respond according to frequency of impact on a 5-point scale coded: never (score 0), hardly ever (score 1), occasionally (score 2), fairly often (score 3) and very often (score 4).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Oral Mucositis Index (MOMI) Scale</measure>
    <time_frame>Baseline weeks to 16 weeks</time_frame>
    <description>Physician assessment using a validated 20 item scale in OLP, is used to rate four types of mucosal changes (atrophy, edema, erythema, and ulceration) in nine anatomical areas of the oral cavity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of Apremilast</measure>
    <time_frame>6 weeks to 16 weeks</time_frame>
    <description>Relationship of adverse events to study treatment. Difference in proportions between the two study arms for each AE at each time point will be assessed and changes in the incidence of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Standardized steroid and anti-fungal rinses used</measure>
    <time_frame>6 weeks to 16 weeks</time_frame>
    <description>Differences in total dexamethasone and nystatin mouthwashes quantity used at each time point between the two study arms will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Mass Index (BMI)</measure>
    <time_frame>Baseline to 16 weeks</time_frame>
    <description>Differences in BMI scores at each time point between two study arms will be assessed</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Oral Lichen Planus</condition>
  <arm_group>
    <arm_group_label>Apremilast</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast</intervention_name>
    <description>Apremilast tablets. Titration will occur in the initial five days of treatment as per dosing in psoriasis as follows: Day 1: 10 mg; Day 2: 20 mg; Day 3: 30 mg; Day 4: 40 mg; Day 5: 50 mg. Day 6 and thereafter patients will be dosed at 60 mg for a total of 12 weeks.</description>
    <arm_group_label>Apremilast</arm_group_label>
    <other_name>Otezla</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo Oral tablets. Patients randomized to the control arm will receive color, taste, shape and odour matched oral placebo. The number of tablets and the days taken is analogous to the intervention arm had they been randomized to the intervention arm.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Each participant must meet all of the following inclusion criteria to participate in this&#xD;
        study:&#xD;
&#xD;
          1. Must be 18 years or older at time of consent.&#xD;
&#xD;
          2. Patients must have clinically active OLP that is being considered for systemic&#xD;
             therapy; and an oral biopsy within the last 12 months of randomization showing a&#xD;
             lichenoid reaction correlating clinically with OLP.&#xD;
&#xD;
          3. Must have failed topical corticosteroids therapy. Topical corticosteroid failure is&#xD;
             defined as receiving a trial of at least 4 weeks of high potency topical&#xD;
             corticosteroids without achieving sufficient improvement by patients.&#xD;
&#xD;
          4. Must be in general good health (except for disease under study) as judged by the&#xD;
             Investigator, based on medical history, physical examination, clinical laboratories,&#xD;
             and urinalysis. (NOTE: The definition of good health means a subject does not have&#xD;
             uncontrolled significant co-morbid conditions). Laboratory work-up includes the&#xD;
             following: complete blood count (CBC), creatinine, albumin, aspartate aminotransferase&#xD;
             (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin,&#xD;
             serum, Beta-HCG (if female), Hepatitis C antibodies and HgbA1C.&#xD;
&#xD;
          5. Male participants must use a recognized effective method of contraception with any&#xD;
             female partner (i.e. at a minimum, barrier plus an additional method of contraception)&#xD;
             while on investigational product and for at least 4 weeks after taking the last dose&#xD;
             of investigational product.&#xD;
&#xD;
          6. Female participants of childbearing potential (FCBP)† must have a negative pregnancy&#xD;
             test at Screening. While on investigational product and for at least 4 weeks after&#xD;
             taking the last dose of investigational product, FCBP who engage in activity in which&#xD;
             conception is possible must use one of the approved contraceptive§ options described&#xD;
             below:&#xD;
&#xD;
               1. Option 1: Any one of the following highly effective methods: hormonal&#xD;
                  contraception (oral, injection, implant, transdermal patch, vaginal ring);&#xD;
                  intrauterine device (IUD); tubal ligation; prior hysterectomy; prior bilateral&#xD;
                  oophorectomy or salpingo-oophorectomy; or partner's vasectomy;&#xD;
&#xD;
                  OR&#xD;
&#xD;
               2. Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of&#xD;
                  natural [animal] membrane [for example, polyurethane]; plus one additional&#xD;
                  barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide;&#xD;
                  or (c) contraceptive sponge with spermicide.&#xD;
&#xD;
                    -  A female of childbearing potential is a sexually mature female who 1) has&#xD;
                       not undergone a hysterectomy (the surgical removal of the uterus) or&#xD;
                       bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not&#xD;
                       been postmenopausal for at least 24 consecutive months (that is, has had&#xD;
                       menses at any time during the preceding 24 consecutive months).&#xD;
&#xD;
                    -  The female subject's chosen form of contraception must be effective by the&#xD;
                       time the female subject is randomized into the study (for example, hormonal&#xD;
                       contraception should be initiated at least 28 days before randomization).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        All participants meeting any of the following exclusion criteria at baseline will be&#xD;
        excluded from participation in this study:&#xD;
&#xD;
          1. Inability to give written consent by the patient or alternative decision maker (will&#xD;
             be assessed at screening visit).&#xD;
&#xD;
          2. Unwillingness to use at least one effective method of contraception due to unknown&#xD;
             fetal risks&#xD;
&#xD;
          3. Use of systemic or topical therapy for OLP other than allowed concomitant care for&#xD;
             symptomatic relief in the past 4 weeks.&#xD;
&#xD;
          4. Hypersensitivity to Apremilast or use of Apremilast within 4 weeks prior to start of&#xD;
             study drug. The contraindications to Apremilast use include prior hypersensitivity&#xD;
             reactions, breast-feeding, and pregnancy (Uptodate.com® accessed August 1st, 2016). An&#xD;
             increased incidence of depression or depressed mood by 1.3% for Apremilast 30 mg BID&#xD;
             (twice a day) (OTEZLA® drug monograph accessed August 1st, 2016) was observed in phase&#xD;
             3 psoriasis studies. Celgene suggests that prescribers should carefully weigh the&#xD;
             risks and benefits in patients with a history of depression and/or suicidal thoughts&#xD;
             or behaviour. The research team will discuss these psychiatric adverse events in the&#xD;
             screening visit where patients/caregivers will be instructed to notify the treating&#xD;
             team for any mood changes.&#xD;
&#xD;
          5. History of palpitations/tachyarrhythmia, severe renal impairment (eGFR less than or&#xD;
             equal to 29), or lactose intolerance within the past 5 years. Apremilast pills contain&#xD;
             lactose; however, the use of concurrent lactase enzyme in lactose intolerant&#xD;
             participants will not be considered and lactose intolerant patients will still be&#xD;
             excluded even if they take lactase enzyme supplementation. This is explained by the&#xD;
             potential exacerbation of gastrointestinal symptoms with Apremilast as an Adverse&#xD;
             Event (AE).&#xD;
&#xD;
          6. CYP3A4 inducers have been shown to diminish Apremilast levels (Lexi-Comp Online™&#xD;
             Interaction Monograph accessed August 1st, 2015); hence, patients will be excluded if&#xD;
             they are on concomitant Carbamazepine, Enzalutamide, Fosphenytoin, Lumacaftor,&#xD;
             Mitotane, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, and Rifapentine.&#xD;
&#xD;
          7. As per Celgene, the presence of any of the following will exclude a subject from&#xD;
             enrollment:&#xD;
&#xD;
               1. Other than disease under study, any clinically significant (as determined by the&#xD;
                  Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric,&#xD;
                  hepatic, renal, hematologic, immunologic disease, or other major disease that is&#xD;
                  currently uncontrolled.&#xD;
&#xD;
               2. Any condition, including the presence of laboratory abnormalities, which would&#xD;
                  place the subject at unacceptable risk if he/she were to participate in the&#xD;
                  study.&#xD;
&#xD;
               3. Prior history of suicide attempt at any time in the subject's life time prior to&#xD;
                  screening or randomization, or major psychiatric illness requiring&#xD;
                  hospitalization within the last 3 years.&#xD;
&#xD;
               4. Pregnant or breast feeding.&#xD;
&#xD;
               5. Active substance abuse or a history of substance abuse within 6 months prior to&#xD;
                  Screening.&#xD;
&#xD;
               6. Malignancy or history of malignancy, except for:&#xD;
&#xD;
                    -  treated [ie, cured] basal cell or squamous cell in situ skin carcinomas;&#xD;
&#xD;
                    -  treated [ie, cured] cervical intraepithelial neoplasia (CIN) or carcinoma in&#xD;
                       situ of cervix with no evidence of recurrence within the previous 5 years.&#xD;
&#xD;
               7. Use of any investigational drug within 4 weeks prior to randomization, or 5&#xD;
                  pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).&#xD;
&#xD;
               8. Prior treatment with apremilast&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hagen Klieb, HBSc, MSc, DMD, FRCD(C)</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Health Sciences Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>February 8, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>June 23, 2020</last_update_submitted>
  <last_update_submitted_qc>June 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sunnybrook Health Sciences Centre</investigator_affiliation>
    <investigator_full_name>Dr. Hagen Klieb</investigator_full_name>
    <investigator_title>Oral Pathologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lichen Planus, Oral</mesh_term>
    <mesh_term>Lichen Planus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apremilast</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03836885
org study id: 049-2018
nct id: NCT03836885
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Apremilast for the management of oral lichen planus.
Oral lichen planus (OLP) affects approximately 1.27% of the general population. Inflammatory
      responses constitute a major component of OLP pathogenesis where targeted therapies play an
      important role in managing this condition. Apremilast is a new well-tolerated and relatively
      safe anti-inflammatory therapy that has been approved for managing psoriasis and psoriatic
      arthritis. Given its safer profile, Apremilast may ameliorate inflammatory responses in
      clinically active OLP without the experience of serious adverse events associated with other
      systemic immunosuppressive therapies used to treat OLP. The plan is to conduct a
      single-center, explanatory, randomized, 16 weeks, parallel group, superiority, blinded,
      placebo-controlled, clinical trial.

      The main objective is treatment success assessment. Other objectives include exploring the
      efficacy of Apremilast in clinically active OLP adult patients considered for systemic
      treatment and failed topical corticosteroid therapy. It is hypothesized that Apremilast will
      induce more treatment success as compared to placebo in patients who failed the standard
      treatment of topical corticosteroids.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Assessing treatment success defined as Physician Global Assessment (PhGA) of 0 or 1
time frame: Baseline to 16 weeks
description: The primary outcome will be assessing treatment success with Apremilast as compared to placebo defined as Physician Global Assessment (PhGA) of 0 or 1.
measure: Achieving complete remission defined as achieving a score of 0 on PhGA scale
time frame: 12 weeks and 16 weeks
description: Complete remission is defined as achieving a score of 0 on PhGA scale
measure: Physician Global Assessment (PhGA)
time frame: Baseline to 16 weeks
description: Physician Global Assessment (PhGA) grading score from 0 to 4. Score of 0 is clear, score of 1 is almost clear, score of 2 is mild disease, score of 3 is moderate disease, and a score of 4 is severe disease.
measure: Patient Assessment (PtA)
time frame: Baseline to 16 weeks
description: Patient Assessment (PtA) grading score from 0 to 4. Score of 0 is clear, score of 1 is almost clear, score of 2 is mild disease, score of 3 is moderate disease, and a score of 4 is severe disease.
measure: Achieving partial response
time frame: Baseline to 12 weeks
description: Percentage of patients who achieve partial response
measure: Visual Analogue Scale (VAS)
time frame: Baseline to 16 weeks
description: Patient assessment of pain score from 0 to 10. VAS is a scale demonstrated by a 10 cm horizontal line marked from 0-10 with the left end marked as no symptoms (0) and the right end marked as worst symptoms (10).
measure: Oral Health Impact Profile (OHIP-14) Scale
time frame: Baseline to 16 weeks
description: Patient assessment of overall disease impact on quality of life is a self-filled validated scale that focuses on seven domains: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability and handicap. Participants will be asked to respond according to frequency of impact on a 5-point scale coded: never (score 0), hardly ever (score 1), occasionally (score 2), fairly often (score 3) and very often (score 4).
measure: Modified Oral Mucositis Index (MOMI) Scale
time frame: Baseline weeks to 16 weeks
description: Physician assessment using a validated 20 item scale in OLP, is used to rate four types of mucosal changes (atrophy, edema, erythema, and ulceration) in nine anatomical areas of the oral cavity
measure: Safety and tolerability of Apremilast
time frame: 6 weeks to 16 weeks
description: Relationship of adverse events to study treatment. Difference in proportions between the two study arms for each AE at each time point will be assessed and changes in the incidence of treatment.
measure: Standardized steroid and anti-fungal rinses used
time frame: 6 weeks to 16 weeks
description: Differences in total dexamethasone and nystatin mouthwashes quantity used at each time point between the two study arms will be assessed
measure: Body Mass Index (BMI)
time frame: Baseline to 16 weeks
description: Differences in BMI scores at each time point between two study arms will be assessed
arm group label: Apremilast
arm group type: Experimental
description: Oral tablet
arm group label: Placebo
arm group type: Placebo Comparator
description: Oral tablet
intervention type: Drug
intervention name: Apremilast
description: Apremilast tablets. Titration will occur in the initial five days of treatment as per dosing in psoriasis as follows: Day 1: 10 mg; Day 2: 20 mg; Day 3: 30 mg; Day 4: 40 mg; Day 5: 50 mg. Day 6 and thereafter patients will be dosed at 60 mg for a total of 12 weeks.
arm group label: Apremilast
other name: Otezla
intervention type: Drug
intervention name: Placebo
description: Placebo Oral tablets. Patients randomized to the control arm will receive color, taste, shape and odour matched oral placebo. The number of tablets and the days taken is analogous to the intervention arm had they been randomized to the intervention arm.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hagen Klieb, HBSc, MSc, DMD, FRCD(C)
role: Principal Investigator
affiliation: Sunnybrook Health Sciences Centre
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Sunnybrook Health Sciences Centre
investigator full name: Dr. Hagen Klieb
investigator title: Oral Pathologist
mesh term: Lichen Planus, Oral
mesh term: Lichen Planus
mesh term: Apremilast
sharing ipd: No