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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 111
- 试验地点
- 1
- 主要终点
- Response Rate of Investigator Global Assessment (IGA) Score of 2 or Lower at Week 16 for CLP, MLP and LPP
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any assessment is performed.
- •Female and male patients ≥ 18 years of age.
- •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.
- •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.
排除标准
- •Clinical history suspicious for lichenoid drug eruption.
- •Lichen planus pigmentosus.
- •Clinical picture or history suspicious of paraneoplastic mucosal lichen planus.
- •Subjects whose lichen planus is a predominantly bullous variant.
- •Mucosal LP of the oral cavity or gastrointestinal involvement requiring the patient to use parenteral nutrition or feeding tube.
- •Clinical picture of scarring alopecia without active inflammation.
- •Clinical picture of burnt-out cicatricial alopecia (alopecia of Brocque).
- •Patients diagnosed with frontal fibrosing alopecia (FFA) without active patches of LPP
- •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).
- •Currently enrolled in any other clinical trial involving any investigational agent or device.
- •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).
- •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.
- •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.
- •Presence of any other skin condition that may affect the evaluations of the study disease.
- •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.
- •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.
研究组 & 干预措施
Cutaneous lichen planus secukinumab 300mg Q4W
Secukinumab 300 mg every 4 weeks provided in pre-filled syringe in cutaneous lichen planus patients
干预措施: secukinumab 300 mg Q4W (Drug)
Cutaneous lichen planus placebo
Placebo in 1ml PFS in cutaneous lichen patients
干预措施: Placebo (Other)
Mucosal lichen planus secukinumab 300 mg Q4W
Secukinumab 300 mg every 4 weeks provided in pre-filled syringe in mucosal lichen planus patients.
干预措施: secukinumab 300 mg Q4W (Drug)
Mucosal lichen planus placebo
Placebo 1 ml PFS in mucosal lichen planus patients
干预措施: Placebo (Other)
Lichen planopilaris secukinumab 300 mg Q4W
Secukinumab 300 mg every 4weeks provided in pre-filled syringe in lichen planopilaris patients.
干预措施: secukinumab 300 mg Q4W (Drug)
Lichen planopilaris placebo
Placebo in 1ml PFS in lichen planopilaris patients
干预措施: Placebo (Other)
Cutaneous lichen planus placebo to secukinumab 300 mg Q2W
Non responder patients on placebo in TP 1 received secukinumab 300 mg Q2W in TP 2
干预措施: secukinumab 300 mg Q2W (Drug)
Mucosal lichen planus placebo to secukinumab 300 mg Q2W
Non responder patients on placebo in TP 1 received secukinumab 300 mg Q2W in TP 2
干预措施: secukinumab 300 mg Q2W (Drug)
Lichen planopilaris placebo to secukinumab 300 mg Q2W
Non responder patients on placebo in TP 1 received secukinumab 300 mg Q2W in TP 2
干预措施: secukinumab 300 mg Q2W (Drug)
结局指标
主要结局
Response Rate of Investigator Global Assessment (IGA) Score of 2 or Lower at Week 16 for CLP, MLP and LPP
时间窗: Baseline up to week 16
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.
次要结局
- 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)(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)(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)(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 - MLP Cohort - Entire Treatment Period (FAS)(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 - MLP Cohort (BOCF) (FAS)(Baseline, Week 16 and Week 32)
- Summary of Baseline Score and Change From Baseline in Reticular Erythematous Ulcerative Score (REU) - MLP Cohort - (BOCF) - Entire Treatment Period(Baseline, Week 16 and Week 32)
- Summary of Baseline Score and Change From Baseline for Scalpdex - LPP Cohort (BOCF) (FAS)(Baseline, Week 16 and Week 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)(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 - LPP Cohort - Entire Treatment Period (FAS)(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32)
- Summary of Baseline Score and Change From Baseline for Patient Assessment of Pain Using Numeric Rating Scale (NRS) by Question -MLP Cohort (BOCF) (FAS)(Baseline, Week 16 and Week 32)
- Summary of Baseline Score and Change From Baseline for Patient Assessment of Pain Using Numeric Rating Scale (NRS) by Question - LPP Cohort (BOCF) (FAS)(Baseline, Week 16 and Week 32)
- Summary of Baseline Score and Change From Baseline in Oral Lichen Planus Symptom Severity Measure (OLPSSM) - MLP Cohort - (BOCF) - Entire Treatment Period(Baseline, Week 16 and Week 32)
- Summary of Baseline Score and Change From Baseline for Lichen Planopilaris Activity Index (LPPAI)- LPP Cohort (BOCF) (FAS)(Baseline, Week 16 and Week 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)(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)(Baseline, Week 16 and Week 32)
- Summary of Baseline Score and Change From Baseline for Patient Assessment of Itch Using Numeric Rating Scale (NRS) by Question - LPP Cohort (BOCF) (FAS)(Baseline, Week 16 and Week 32)
- Summary of Baseline Score and Change From Baseline for Patient Assessment of Pain Using Numeric Rating Scale (NRS) by Question - CLP Cohort (BOCF) (FAS)(Baseline, Week 16 and Week 32)