Lichen Planus: Cutaneous Lichen Planus, Mucosal Lichen Planus and Lichen Planopilaris Clinical Trial
— PRELUDEOfficial 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
| Verified date | July 2023 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 111 |
| Est. completion date | May 3, 2022 |
| Est. primary completion date | November 16, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| France | Novartis Investigative Site | Bordeaux Cedex | |
| France | Novartis Investigative Site | Chambray les Tours | |
| France | Novartis Investigative Site | Lyon | |
| France | Novartis Investigative Site | Marseille Cedex 05 | |
| France | Novartis Investigative Site | Nantes Cedex 1 | |
| France | Novartis Investigative Site | Nice Cedex | |
| France | Novartis Investigative Site | Paris Cedex 10 | |
| France | Novartis Investigative Site | Rouen Cedex | |
| France | Novartis Investigative Site | Toulouse | |
| Germany | Novartis Investigative Site | Aachen | |
| Germany | Novartis Investigative Site | Berlin | |
| Germany | Novartis Investigative Site | Bramsche | |
| Germany | Novartis Investigative Site | Erlangen | |
| Germany | Novartis Investigative Site | Frankfurt | |
| Germany | Novartis Investigative Site | Halle | |
| Germany | Novartis Investigative Site | Hamburg | |
| Germany | Novartis Investigative Site | Luebeck | |
| Germany | Novartis Investigative Site | Marburg | |
| Germany | Novartis Investigative Site | Muenchen | |
| Germany | Novartis Investigative Site | Wuerzburg | |
| United States | Novartis Investigative Site | Birmingham | Alabama |
| United States | Novartis Investigative Site | Charleston | South Carolina |
| United States | Novartis Investigative Site | Cromwell | Connecticut |
| United States | Novartis Investigative Site | East Windsor | New Jersey |
| United States | Novartis Investigative Site | Forest Hills | New York |
| United States | Novartis Investigative Site | Houston | Texas |
| United States | Novartis Investigative Site | Jacksonville | Florida |
| United States | Novartis Investigative Site | Las Vegas | Nevada |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | New York | New York |
| United States | Novartis Investigative Site | Omaha | Nebraska |
| United States | Novartis Investigative Site | Pflugerville | Texas |
| United States | Novartis Investigative Site | Portland | Oregon |
| United States | Novartis Investigative Site | Snellville | Georgia |
| United States | Novartis Investigative Site | Thousand Oaks | California |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, France, Germany,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | Baseline up to week 16 | |
| Secondary | 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. | Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 | |
| Secondary | 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. | Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 | |
| Secondary | 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) | 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. | Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 | |
| Secondary | 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 | Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 | |
| Secondary | 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. | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32 | |
| Secondary | 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. | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32 | |
| Secondary | Number (%) of Subjects With Dermatology Life Quality Index Response Scores of 0 to 1 up to Week 32 - LPP 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. | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, and 32 | |
| Secondary | 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". | Baseline, Week 16 and Week 32 | |
| Secondary | Summary of Baseline Score and Change From Baseline for Patient Assessment of Itch Using Numeric Rating Scale (NRS) by Question - MLP 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". | Baseline, Week 16 and Week 32 | |
| Secondary | Summary of Baseline Score and Change From Baseline for Patient Assessment of Itch Using Numeric Rating Scale (NRS) by Question - LPP 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". | Baseline, Week 16 and Week 32 | |
| Secondary | Summary of Baseline Score and Change From Baseline for Patient Assessment of Pain Using Numeric Rating Scale (NRS) by Question - CLP Cohort (BOCF) (FAS) | Pain is assessed with the following questions: • "Overall, how severe was your lichen planus-related pain during the past 24 hours?" • "How severe was your lichen planus-related pain at the worst moment during the past 24 hours?" • "Overall, how bothered were you by your lichen planus-related pain during the past 24 hours?" Answers are given on a numeric rating scale (NRS) from 0 to 10, with 0 meaning "no pain" and 10 meaning "the worst pain imaginable". | Baseline, Week 16 and Week 32 | |
| Secondary | Summary of Baseline Score and Change From Baseline for Patient Assessment of Pain Using Numeric Rating Scale (NRS) by Question -MLP Cohort (BOCF) (FAS) | Pain is assessed with the following questions: • "Overall, how severe was your lichen planus-related pain during the past 24 hours?" • "How severe was your lichen planus-related pain at the worst moment during the past 24 hours?" • "Overall, how bothered were you by your lichen planus-related pain during the past 24 hours?" Answers are given on a numeric rating scale (NRS) from 0 to 10, with 0 meaning "no pain" and 10 meaning "the worst pain imaginable". | Baseline, Week 16 and Week 32 | |
| Secondary | Summary of Baseline Score and Change From Baseline for Patient Assessment of Pain Using Numeric Rating Scale (NRS) by Question - LPP Cohort (BOCF) (FAS) | Pain is assessed with the following questions: • "Overall, how severe was your lichen planus-related pain during the past 24 hours?" • "How severe was your lichen planus-related pain at the worst moment during the past 24 hours?" • "Overall, how bothered were you by your lichen planus-related pain during the past 24 hours?" Answers are given on a numeric rating scale (NRS) from 0 to 10, with 0 meaning "no pain" and 10 meaning "the worst pain imaginable". | Baseline, Week 16 and Week 32 | |
| Secondary | Summary of Baseline Score and Change From Baseline in Reticular Erythematous Ulcerative Score (REU) - MLP Cohort - (BOCF) - Entire Treatment Period | REU measured disease severity based on 3 dimensions: reticulation, erythema and ulceration for all subjects in the MLP cohort who had an oral presentation of the disease. The total score ranged from 0-115 with higher values corresponding to higher activity of the disease. | Baseline, Week 16 and Week 32 | |
| Secondary | Summary of Baseline Score and Change From Baseline in Oral Lichen Planus Symptom Severity Measure (OLPSSM) - MLP Cohort - (BOCF) - Entire Treatment Period | OLPSSM is a self-administered assessment of the symptom experience of subjects with oral LP in clinical studies. It includes 7 triggers contributing to soreness of oral lichen planus: Brushing teeth, eating food, drinking liquids, smiling, breathing through mouth, talking and touching. These 7 items contributed equally to a total OLP symptom severity score, ranging from 0 to 28, with higher scores indicating worse severity. | Baseline, Week 16 and Week 32 | |
| Secondary | Summary of Baseline Score and Change From Baseline for Lichen Planopilaris Activity Index (LPPAI)- LPP Cohort (BOCF) (FAS) | The LPPAI assesses symptoms (pruritus, pain, burning), signs (erythema, perifollicular erythema and scale), a measure of activity (pull test) and extension of disease. These subjective and objective measures are assigned numeric values to establish a disease activity score. The total score ranges from 0 to 10, with higher scores corresponding to higher disease activity | Baseline, Week 16 and Week 32 | |
| Secondary | Summary of Baseline Score and Change From Baseline for Scalpdex - LPP Cohort (BOCF) (FAS) | Scalpdex is a self-administered, health-related quality of life instrument originally developed for scalp dermatitis. This survey includes 23 items, each item scored on a scale of 0-100, where 0=never, 25=rarely, 50=sometimes, 75=often and 100=all the time. The 23 items pertain to 3 domains: symptom, emotions and functioning. Subjects were asked to score themselves on how true each of the 23 statements has been for them over the past four weeks. the total score is the average of the scores of the 23 items. A higher total score indicated a higher impairment in quality of life. | Baseline, Week 16 and Week 32 |