PoC Study to Evaluate the Efficacy and Safety of Secukinumab 300 mg in Patients With Lichen Planus

Novartis Pharmaceuticals111 enrolled

Overview

The primary purpose of the proof of concept study is to elucidate the efficacy of secukinumab in the treatment of adult patients with biopsy-proven lichen planus not adequately controlled by topical therapies, and to assess the safety and tolerability over 32 weeks.

This was a 32-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial which assessed the efficacy and safety of secukinumab 300 mg in two different dosing regimens: every 4 weeks (Q4W) and every 2 weeks (Q2W) in approximately 111 patients with biopsy-proven forms of lichen planus. There was a screening period (up to 4 weeks prior to baseline), a treatment period 1 (baseline to Week 16), a treatment period 2 (Week 16 to Week 32) and a follow-up period (8 weeks after Week 32).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

111

Conditions

Lichen Planus: Cutaneous Lichen Planus, Mucosal Lichen Planus and Lichen Planopilaris

Interventions

secukinumab 300 mg Q4WDRUG

secukinumab 300 mg administered every four weeks (Q4W) via a pre-filled syringe.

secukinumab 300 mg Q2WDRUG

secukinumab 300 mg administered every two weeks (Q2W) via a pre-filled syringe.

PlaceboOTHER

Matching placebo administered via a pre-filled syringe

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Written informed consent must be obtained before any assessment is performed. 2. Female and male patients ≥ 18 years of age. 3. Subjects must have biopsy-confirmed forms of cutaneous lichen planus (CLP), 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. If using any of the allowed topical treatments on the affected areas, the dose and application frequency should remain stable for 2 weeks prior to randomization and until Week 16. Exclusion Criteria: 1. Clinical history suspicious for lichenoid drug eruption. 2. Lichen planus pigmentosus. 3. Clinical picture or history suspicious of paraneoplastic mucosal lichen planus. 4. Subjects whose lichen planus is a predominantly bullous variant. 5. Mucosal LP of the oral cavity or gastrointestinal involvement requiring the patient to use parenteral nutrition or feeding tube. 6. Clinical picture of scarring alopecia without active inflammation. 7. Clinical picture of burnt-out cicatricial alopecia (alopecia of Brocque). 8. Patients diagnosed with frontal fibrosing alopecia (FFA) without active patches of LPP 9. Clinical picture of LPP in patients who have already failed 3 or more systemic immunosuppressive or immunomodulatory agents (e.g. systemic steroids, hydroxychloroquine, cyclosporine, methotrexate and mycophenolate mofetil). 10. Currently enrolled in any other clinical trial involving any investigational agent or device. 11. Previous exposure to any other biologic drug directly targeting IL-17A or IL-17RA (e.g. secukinumab, ixekizumab or brodalumab) or IL-23/p19 (e.g. tildrakizumab, guselkumab, risankizumab). 12. Diagnosis of active infectious diseases of the skin, scalp or mucosa (for example bacterial, viral or fungal infections of the mouth) that may interfere with the assessment of the study disease or require treatment with prohibited medications. 13. Diagnosis of active inflammatory diseases of the skin, scalp or mucosa other than lichen planus that may interfere with the assessment of the study disease or require treatment with prohibited medications. 14. Presence of any other skin condition that may affect the evaluations of the study disease. 15. Underlying conditions (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) and/or presence of laboratory abnormalities which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy. 16. Current, severe, progressive or uncontrolled diseases that render the patient unsuitable for the trial, including any medical or psychiatric condition that, in the Investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.

Locations (35)

Outcomes

Primary Outcomes

Response Rate of Investigator Global Assessment (IGA) Score of 2 or Lower at Week 16 for CLP, MLP and LPP

Number of treatment responders at week 16, where response is defined as an Investigator's Global Assessment (IGA) score of 2 or lower at Week 16. IGA is measured on a scale from 0 - 4 with 0 = Clear, 1 = Minimal; 2 = Mild; 3 = Moderate; and 4 = Severe with 0 being best score and 4 being worst score. CLP=Cutaneous lichen planus, MLP=Mucosal lichen planus, LPP=Lichen planopilaris. Posterior median and 95% credible interval (instead of 95% confidence interval) were derived using Bayesian method based on beta-binomial model.

Time frame: Baseline up to week 16

Secondary Outcomes

Number (%) of Subjects With IGA ≤ 2 Response, IGA ≥2 Points Improvement Response, and IGA 0 or 1 Response by Visit - CLP Cohort (BOCF)- Entire Treatment Period (FAS)

Number of subjects with IGA of 2 or lower, improvement in the IGA score of at least 2 points, or IGA score of 0/1. IGA is measured on a scale from 0-4 with 0=Clear, 1=minimal, 2=mild, 3=moderate, and 4=severe with 0 being best score and 4 being worst score.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32

Number (%) of Subjects With IGA ≤ 2 Response, IGA ≥2 Points Improvement Response, and IGA 0 or 1 Response by Visit - MLP Cohort (BOCF)- Entire Treatment Period (FAS)

Number of subjects with IGA of 2 of lower, improvement in the IGA score of at least 2 points, or IGA score of 0/1. IGA is measured on a scale from 0-4 with 0=Clear, 1=minimal, 2=mild, 3=moderate, and 4=severe with 0 being best score and 4 being worst score.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32

Number (%) of Subjects With IGA ≤ 2 Response, IGA ≥2 Points Improvement Response, and IGA 0 or 1 Response by Visit - LPP Cohort (BOCF)- Entire Treatment Period (FAS)

Data from ClinicalTrials.gov

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Novartis Investigative Site

Birmingham, Alabama, United States

Novartis Investigative Site

Thousand Oaks, California, United States

Novartis Investigative Site

Cromwell, Connecticut, United States

Novartis Investigative Site

Jacksonville, Florida, United States

Novartis Investigative Site

Miami, Florida, United States

Novartis Investigative Site

Snellville, Georgia, United States

Novartis Investigative Site

Omaha, Nebraska, United States

Novartis Investigative Site

Las Vegas, Nevada, United States

Novartis Investigative Site

East Windsor, New Jersey, United States

Novartis Investigative Site

Forest Hills, New York, United States

...and 25 more locations

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32

Number (%) of Subjects in Each Category in Physician´s Assessment of Surface Area of Disease (PSAD) - CLP (BOCF) - Entire Treatment Period (FAS)

The Physician Assessment of Surface Area of Disease (PSAD) evaluates the extent of cutaneous lesions estimated by investigator or qualified designee. Assessment scores range from 0-5, with lower scores corresponding to lower percentages of surface area with disease: 0=clear, 1=\<2%, 2=2-9%, 3=10-29%, 4=30-50%, 5=\>50% of total body surface

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32

Number (%) of Subjects With Dermatology Life Quality Index Response Scores of 0 to 1 up to Week 32 - CLP Cohort - Entire Treatment Period (FAS)

The Dermatology Life Quality Index (DLQI) is a 10-item general dermatology disability index designed to assess health-related quality of life (HRQoL) in adult subjects with skin diseases such as eczema, psoriasis, acne, and viral warts. The measure is self-administered and includes domains of daily activities, leisure, personal relationships, symptoms and feelings, treatment, and work/school. The recall period is the last week, and the instrument requires 1 to 2 minutes for completion. Each item has four response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions. Scores range from 0 to 30, with higher scores indicating greater HRQoL impairment.

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32

Number (%) of Subjects With Dermatology Life Quality Index Response Scores of 0 to 1 up to Week 32 - MLP Cohort - Entire Treatment Period (FAS)

The DLQI is a 10-item general dermatology disability index designed to assess health-related quality of life (HRQoL) in adult subjects with skin diseases such as eczema, psoriasis, acne, and viral warts (Finlay and Khan 1994). The measure is self-administered and includes domains of daily activities, leisure, personal relationships, symptoms and feelings, treatment, and work/school. The recall period is the last week, and the instrument requires 1 to 2 minutes for completion. Each item has four response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions. Scores range from 0 to 30, with higher scores indicating greater HRQoL impairment.

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32

Number (%) of Subjects With Dermatology Life Quality Index Response Scores of 0 to 1 up to Week 32 - LPP Cohort - Entire Treatment Period (FAS)

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32

Summary of Baseline Score and Change From Baseline for Patient Assessment of Itch Using Numeric Rating Scale (NRS) by Question - CLP Cohort (BOCF) (FAS)

Itch is assessed with the following questions: • "Overall, how severe was your lichen planus-related itching during the past 24 hours?" • "How severe was your lichen planus-related itching at the worst moment during the past 24 hours?" • "Overall, how bothered were you by your lichen planus-related itching during the past 24 hours?" Answers are given on a numeric rating scale (NRS) from 0 to 10, with 0 meaning "no itch" and 10 meaning "the worst itch imaginable".