Apremilast - Oral Lichen Planus Trial

NCT03836885 | Withdrawn Phase 2 DMC

• 1 other identifier: 049-2018
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Apremilast for the management of oral lichen planus.

Conditions

Oral Lichen Planus

Outcome Measures

Primary Outcomes (1)

• Assessing treatment success defined as Physician Global Assessment (PhGA) of 0 or 1

  The primary outcome will be assessing treatment success with Apremilast as compared to placebo defined as Physician Global Assessment (PhGA) of 0 or 1.

  Baseline to 16 weeks

Secondary Outcomes (10)

• Achieving complete remission defined as achieving a score of 0 on PhGA scale

  12 weeks and 16 weeks

• Physician Global Assessment (PhGA)

  Baseline to 16 weeks

• Patient Assessment (PtA)

  Baseline to 16 weeks

• Achieving partial response

  Baseline to 12 weeks

• Visual Analogue Scale (VAS)

  Baseline to 16 weeks

Study Arms (2)

Apremilast

EXPERIMENTAL

Oral tablet

Drug: Apremilast

Placebo

PLACEBO COMPARATOR

Oral tablet

Drug: Placebo

Interventions

Apremilast DRUG

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.

Also known as: Otezla

Apremilast

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be 18 years or older at time of consent.
• Patients must have clinically active OLP that is being considered for systemic therapy; and an oral biopsy within the last 12 months of randomization showing a lichenoid reaction correlating clinically with OLP.
• Must have failed topical corticosteroids therapy. Topical corticosteroid failure is defined as receiving a trial of at least 4 weeks of high potency topical corticosteroids without achieving sufficient improvement by patients.
• Must be in general good health (except for disease under study) as judged by the Investigator, based on medical history, physical examination, clinical laboratories, and urinalysis. (NOTE: The definition of good health means a subject does not have uncontrolled significant co-morbid conditions). Laboratory work-up includes the following: complete blood count (CBC), creatinine, albumin, aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin, serum, Beta-HCG (if female), Hepatitis C antibodies and HgbA1C.
• Male participants must use a recognized effective method of contraception with any female partner (i.e. at a minimum, barrier plus an additional method of contraception) while on investigational product and for at least 4 weeks after taking the last dose of investigational product.
• Female participants of childbearing potential (FCBP)† must have a negative pregnancy test at Screening. While on investigational product and for at least 4 weeks after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive§ options described below:
• Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; prior hysterectomy; prior bilateral oophorectomy or salpingo-oophorectomy; or partner's vasectomy;
• Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]; plus one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
• A female of childbearing potential is a sexually mature female who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months).
• The female subject's chosen form of contraception must be effective by the time the female subject is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization).

You may not qualify if:

• Inability to give written consent by the patient or alternative decision maker (will be assessed at screening visit).
• Unwillingness to use at least one effective method of contraception due to unknown fetal risks
• Use of systemic or topical therapy for OLP other than allowed concomitant care for symptomatic relief in the past 4 weeks.
• Hypersensitivity to Apremilast or use of Apremilast within 4 weeks prior to start of study drug. The contraindications to Apremilast use include prior hypersensitivity reactions, breast-feeding, and pregnancy (Uptodate.com® accessed August 1st, 2016). An increased incidence of depression or depressed mood by 1.3% for Apremilast 30 mg BID (twice a day) (OTEZLA® drug monograph accessed August 1st, 2016) was observed in phase 3 psoriasis studies. Celgene suggests that prescribers should carefully weigh the risks and benefits in patients with a history of depression and/or suicidal thoughts or behaviour. The research team will discuss these psychiatric adverse events in the screening visit where patients/caregivers will be instructed to notify the treating team for any mood changes.
• History of palpitations/tachyarrhythmia, severe renal impairment (eGFR less than or equal to 29), or lactose intolerance within the past 5 years. Apremilast pills contain lactose; however, the use of concurrent lactase enzyme in lactose intolerant participants will not be considered and lactose intolerant patients will still be excluded even if they take lactase enzyme supplementation. This is explained by the potential exacerbation of gastrointestinal symptoms with Apremilast as an Adverse Event (AE).
• CYP3A4 inducers have been shown to diminish Apremilast levels (Lexi-Comp Online™ Interaction Monograph accessed August 1st, 2015); hence, patients will be excluded if they are on concomitant Carbamazepine, Enzalutamide, Fosphenytoin, Lumacaftor, Mitotane, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, and Rifapentine.
• As per Celgene, the presence of any of the following will exclude a subject from enrollment:
• Other than disease under study, 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.
• Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study.
• Prior history of suicide attempt at any time in the subject's life time prior to screening or randomization, or major psychiatric illness requiring hospitalization within the last 3 years.
• Pregnant or breast feeding.
• Active substance abuse or a history of substance abuse within 6 months prior to Screening.
• Malignancy or history of malignancy, except for:
• treated \[ie, cured\] basal cell or squamous cell in situ skin carcinomas;
• treated \[ie, cured\] cervical intraepithelial neoplasia (CIN) or carcinoma in situ of cervix with no evidence of recurrence within the previous 5 years.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Celgene: collaborator
• Sunnybrook Research Institute: collaborator

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

MeSH Terms

Conditions

Lichen Planus, Oral

Interventions

apremilast

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Lichen Planus; Lichenoid Eruptions; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Hagen Klieb, HBSc, MSc, DMD, FRCD(C)

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oral Pathologist

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 11, 2019
• Study Start: November 21, 2019
• Primary Completion: April 22, 2020
• Study Completion: April 22, 2020
• Last Updated: June 25, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)