Clinical trial NCT04300296: PoC Study to Evaluate the Efficacy and Safety of Secukinumab 300 mg in Patients With Lichen Planus
Official title: A Proof of Concept Study to Evaluate the Efficacy, Safety and Tolerability of Secukinumab 300 mg Over 32 Weeks in Adult Patients With Biopsy-proven Forms of Lichen Planus Not Adequately Controlled With Topical Therapies - PRELUDE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lichen Planus: Cutaneous Lichen Planus, Mucosal Lichen Planus and Lichen Planopilaris
Keywords: Lichen planus
CLP
MLP
LPP
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-03-09
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PoC study, 32-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial assessing the efficacy and safety of secukinumab 300 mg in two different dosing regimens in 108 patients with biopsy-proven forms of lichen planus.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Response Rate of Investigator Global Assessment (IGA) Score of 2 or Lower at Week 16 for CLP, MLP and LPP
timeFrame: Baseline up to week 16
Secondary outcomes:
measure: 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)
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
measure: 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)
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
measure: 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)
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
measure: Number (%) of Subjects in Each Category in Physician´s Assessment of Surface Area of Disease (PSAD) - CLP (BOCF) - Entire Treatment Period (FAS)
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
measure: Number (%) of Subjects With Dermatology Life Quality Index Response Scores of 0 to 1 up to Week 32 - CLP Cohort - Entire Treatment Period (FAS)
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32
measure: Number (%) of Subjects With Dermatology Life Quality Index Response Scores of 0 to 1 up to Week 32 - MLP Cohort - Entire Treatment Period (FAS)
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32
measure: Number (%) of Subjects With Dermatology Life Quality Index Response Scores of 0 to 1 up to Week 32 - LPP Cohort - Entire Treatment Period (FAS)
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32
measure: Summary of Baseline Score and Change From Baseline for Patient Assessment of Itch Using Numeric Rating Scale (NRS) by Question - CLP Cohort (BOCF) (FAS)
timeFrame: Baseline, Week 16 and Week 32
measure: Summary of Baseline Score and Change From Baseline for Patient Assessment of Itch Using Numeric Rating Scale (NRS) by Question - MLP Cohort (BOCF) (FAS)
timeFrame: Baseline, Week 16 and Week 32
measure: Summary of Baseline Score and Change From Baseline for Patient Assessment of Itch Using Numeric Rating Scale (NRS) by Question - LPP Cohort (BOCF) (FAS)
timeFrame: Baseline, Week 16 and Week 32
measure: Summary of Baseline Score and Change From Baseline for Patient Assessment of Pain Using Numeric Rating Scale (NRS) by Question - CLP Cohort (BOCF) (FAS)
timeFrame: Baseline, Week 16 and Week 32
measure: Summary of Baseline Score and Change From Baseline for Patient Assessment of Pain Using Numeric Rating Scale (NRS) by Question -MLP Cohort (BOCF) (FAS)
timeFrame: Baseline, Week 16 and Week 32
measure: Summary of Baseline Score and Change From Baseline for Patient Assessment of Pain Using Numeric Rating Scale (NRS) by Question - LPP Cohort (BOCF) (FAS)
timeFrame: Baseline, Week 16 and Week 32
measure: Summary of Baseline Score and Change From Baseline in Reticular Erythematous Ulcerative Score (REU) - MLP Cohort - (BOCF) - Entire Treatment Period
timeFrame: Baseline, Week 16 and Week 32
measure: Summary of Baseline Score and Change From Baseline in Oral Lichen Planus Symptom Severity Measure (OLPSSM) - MLP Cohort - (BOCF) - Entire Treatment Period
timeFrame: Baseline, Week 16 and Week 32
measure: Summary of Baseline Score and Change From Baseline for Lichen Planopilaris Activity Index (LPPAI)- LPP Cohort (BOCF) (FAS)
timeFrame: Baseline, Week 16 and Week 32
measure: Summary of Baseline Score and Change From Baseline for Scalpdex - LPP Cohort (BOCF) (FAS)
timeFrame: Baseline, Week 16 and Week 32
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Thousand Oaks
country: United States
facility: Novartis Investigative Site
state: California
city: Cromwell
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Snellville
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Las Vegas
country: United States
facility: Novartis Investigative Site
state: Nevada
city: East Windsor
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Forest Hills
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Charleston
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Pflugerville
country: United States
facility: Novartis Investigative Site
state: Texas
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Chambray les Tours
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille Cedex 05
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Nice Cedex
country: France
facility: Novartis Investigative Site
city: Paris Cedex 10
country: France
facility: Novartis Investigative Site
city: Rouen Cedex
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bramsche
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Halle
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Luebeck
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
Study officials:
References:
citation: Miteva M, Nadji M, Billero V, LaSenna C, Nattkemper L, Romanelli P. IL-17 Expression in the Perifollicular Fibrosis in Biopsies From Lichen Planopilaris. Am J Dermatopathol. 2022 Dec 1;44(12):874-878. doi: 10.1097/DAD.0000000000002316. Epub 2022 Sep 27.