Upadacitinib in Adult Patients With Erosive Mucosal Lichen Planus and Lichen Planopilaris: a Prospective Multicenter Randomized Placebo-controlled Study. (Upa_LP)

Centre Hospitalier Universitaire de Nice

Status and phase: Begins enrollment this month; Phase 2

Conditions: Lichen Penis Planus

Treatments: Drug: Upadacitinib; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07492251

25-PP-10

Details and patient eligibility

About

Lichen planus (LP) is a common immune-mediated skin disease with a prevalence of 1-2% in the general population. It can present with a broad spectrum of clinical manifestations affecting primarily the skin (cutaneous LP [CLP]), the mucosae (mucosal LP [MLP]), hair follicles (lichen planopilaris [LPP]), or nails (nail lichen planus (NLP). The often treatment-refractory nature of the disease, the pronounced itch of CLP lesions, the pain of erosive MLP lesions, and the visible impact of NLP or LPP induced hair loss are well reflected by the poor quality of life (QoL) of patients with LP. There is no treatment for LP approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). The pathogenesis of LP is now better understood. LP lesions are infiltrated with T cells, including CD8+ and CD4+ populations. CD8+ T cells, mainly located around the basal layer of the epidermis, can trigger apoptosis of epidermal keratinocytes. Recent data underline the role of the Th1 response in LP suggesting that oral inhibitors of Janus Kinase 1 (JAK1) could be of interest. This is supported by isolated cases and open series of successful treatment of CLP, erosive MLP and LPP by several topical and oral JAK inhibitors (JAKi), including upadacitinib. However, the results are variable depending on patient characteristics, type of JAKi and doses used. Upadacitinib is a selective JAK1 inhibitor and provides a good safety profile. We hypothesize that it could be an effective option for LPP and erosive MLP, the most severe and disabling forms of LP.

This is a multicenter, randomized, double-blind, placebo-controlled, parallel- group trial assessing the efficacy and safety of upadacitinib 30 mg in patients with biopsy-proven LPP or erosive MLP.

Enrollment: 56 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Written informed consent must be obtained before any assessment is performed

2. Female and male patients ≥ 18 years and < 65 years old at Baseline Visit

3. Subjects must have biopsy-confirmed forms of mucosal lichen planus (MLP) or active lichen planopilaris (LPP) eligible for systemic therapy based on the following criteria:

   • Rated IGA of ≥ 3 (moderate or severe) AND
   • Inadequate response to topical corticosteroids of high - ultrahigh potency in the opinion of the investigator

4. A negative serum pregnancy test for all female subjects considered to be of childbearing potential at the Screening Visit and a negative urine pregnancy test at baseline prior to the first dose of study drug.

Exclusion criteria

1. Clinical history suspicious for lichenoid drug eruption

2. Clinical picture or history suspicious of paraneoplastic mucosal lichen planus

3. Mucosal lichen planus of the oral cavity or gastrointestinal involvement requiring the patient to use parenteral nutrition or feeding tube

4. Clinical picture of burnt-out cicatricial alopecia (alopecia of Brocq)

5. Patients diagnosed with frontal fibrosing alopecia (FFA) without active patches of LPP

6. History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months prior to Baseline.

7. Meeting any of the following conditions at Baseline:

   1. Three or more prior episodes of herpes zoster, or one or more episodes of disseminated herpes zoster;
   2. One or more prior episodes of disseminated herpes simplex (including eczema herpeticum);
   3. Human immunodeficiency virus (HIV) infection, defined as confirmed positive anti-HIV antibody (HIV Ab) test or a positive HIV Ab/Ag test
   4. Active tuberculosis (TB) or meet TB exclusionary parameters;
   5. Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to the Baseline Visit;
   6. Chronic recurring infection and/or active viral infection that, based on the investigator's clinical assessment, makes the subject an unsuitable candidate for the study;
   7. Hepatitis B virus (HBV) and hepatitis C virus (HCV) screening values that meet the following criteria at the most recent testing prior to the first dose of study treatment:
   8. HBV: hepatitis B surface antigen (HBs Ag) positive (+) test or detectable HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for subjects who are hepatitis B core antibody (HBc Ab) positive (+);
   9. HCV: detectable HCV ribonucleic acid (RNA) in any subject with anti-HCV antibody (HCV Ab).

8. At Baseline any of the following medical diseases or disorders:

   1. Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, aorto-coronary bypass surgery, or venous thromboembolism;
   2. History of an organ transplant which requires continued immunosuppression;
   3. History of an allergic reaction or significant sensitivity to constituents of the study drug and/or other products in the same class;
   4. History of gastrointestinal (GI) perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment;
   5. Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery (including sleeve gastrectomy); subjects with a history of gastric banding/segmentation are not excluded;
   6. History of malignancy except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix;

9. Females of child-bearing potential who meet the following criteria for pregnancy testing:

   1. Subjects with a positive serum pregnancy test at the Screening Visit or a positive urine pregnancy test at Baseline prior to the first dose of study treatment (local practices may require serum pregnancy testing at Baseline).
   2. Subjects with a borderline serum pregnancy test at Screening must have absence of clinical suspicion of pregnancy or other pathological causes of borderline results and a serum pregnancy test ≥ 3 days later to document continued lack of a positive result (unless inclusion of subjects with a borderline pregnancy test may be prohibited by local requirements).
   3. Subjects with a urine pregnancy test at Baseline that is borderline or ambiguous must have a serum pregnancy test performed. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

10. Female subjects of childbearing potential who are not able and/or willing to practice at least 1 protocol-specified method of birth control that is highly effective from Study Day 1 through at least 30 days after the last dose of study drug (local practices may require an additional method of contraception). Female subjects of non-childbearing potential do not need to use birth control.

11. Female subjects who are pregnant, breastfeeding, or considering becoming pregnant or donating eggs during the study and for 30 days after the last dose of study drug.

12. Subjects who have been treated with any investigational drug of chemical or biologic nature within 30 days or five half-lives (whichever is longer) prior to the first dose of study drug or who are currently enrolled in another interventional clinical study.

13. Subjects with systemic use of known strong cytochrome P450 3A (CYP3A) inhibitors or strong CYP3A inducers 30 days prior to study treatment administration (refer to the Table in section 5. for examples of commonly used strong CYP3A inhibitors and inducers)

14. Subjects who have received any live vaccine with replicating potential within 30 days prior to the first dose of study drug, or have expected need of vaccination with any live vaccine with replicating potential during study participation including at least 30 days after the last dose of study drug. Live vaccines that are incapable of replicating are permitted.

15. Screening laboratory values that meet the following criteria at the most recent testing prior to the first dose of study drug:

    1. Serum aspartate transaminase (AST) > 2 × ULN;
    2. Serum alanine transaminase (ALT) > 2 × ULN;
    3. Estimated glomerular filtration rate (GFR) by simplified 4-variable MDRD formula < 30 mL/min/1.73 m2;
    4. Total white blood cell (WBC) count < 2,500/µL;
    5. Absolute neutrophil count (ANC) < 1,200/µL;
    6. Platelet count < 100,000/µL;
    7. Absolute lymphocyte count < 750/µL;
    8. Hemoglobin < 9 g/dL.

16. History of or current clinically significant medical conditions or any other reason that in the opinion of the Investigator would interfere with the subject's participation in this study, would place the subject at risk by participating in the study or would make the subject an unsuitable candidate to receive study drug, also with regard to the European Commission Decision as of 10 March 2023 on measures to minimize risk of serious side effects with Janus kinase inhibitors (EMA/142279/2023).

17. Withdrawal of the informed consent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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56 participants in 2 patient groups, including a placebo group

Drug

Experimental group

Description:

28 patients for each condition (56 total) to upadacitinib 30mg QD for 16 weeks.

Treatment:

Drug: Upadacitinib

Placebo

Placebo Comparator group

Description:

28 patients to placebo n30mg QD for 16 weeks.

Treatment:

Drug: Placebo