Safety, Tolerability, and Efficacy Study of LFX453 in Actinic Keratosis Patients

Study Overview
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Brief Summary
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This is a randomized, vehicle controlled, active comparator, parallel group, study with a total duration of 24 weeks including screening and follow-up. Study drug is applied topically for 2 cycles of 4 week treatment, separated by 4 weeks off-treatment. Assessors of study endpoints are blinded to treatment allocation.

Official Title
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A Randomized, Vehicle Controlled, Active Comparator, Parallel Group Study to Evaluate Safety, Tolerability and Preliminary Efficacy of Topical LFX453 Formulations in Patients With Actinic Keratosis

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: Investigational Treatment
* Drug: Active comparator


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male patients, and female patients of non-childbearing potential, age ≥ 18 to ≤ 75 years (at the time of the screening visit), and in general good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening Patients with at least five clinically typical, visible or palpable non-hyperkeratotic AK lesions within a contiguous area of 25 cm2, or within 2 areas for a maximum total of 25cm2, on the face (at least 2 cm from the periocular areas, lips, nares and ears) and/or balding scalp Presence of at least one additional visible or palpable non hyperkeratotic AK lesion outside of the selected area amenable to the collection of a skin biopsy, and located at least at 2 cm from the limits of the area to receive treatment Male patients had to agree to use adequate contraception for the duration of the study. Key Exclusion Criteria: Known hypersensitivity to any constituents of the study drugs (including local anesthetics if consenting to biopsies) or known allergies to imiquimod or to drugs of similar chemical classes or history of serious allergic reaction. Presence of atopic dermatitis, eczema, psoriasis, rosacea or other possible confounding skin conditions on face or balding scalp even outside of the treatment area. Invasive tumors within the treatment area, e.g., merkel cell carcinoma, melanoma, squamous cell carcinoma (SCC), basal cell carcinoma, the latter being accepted if completely surgically removed. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. History of hypertrophic scarring. Concurrent disease that suppresses the immune system.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LFX453 0.1% NMC<br>LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications | Drug: Investigational Treatment<br>* Topical application for two treatment cycles with twice daily applications, separated by a 4 week treatment pause and followed by 8 week treatment free follow-up.<br>|
| Experimental: LFX453 0.15% LCC<br>LFX453 0.15% liquid crystal cream (LCC) Twice daily applications | Drug: Investigational Treatment<br>* Topical application for two treatment cycles with twice daily applications, separated by a 4 week treatment pause and followed by 8 week treatment free follow-up.<br>|
| Placebo Comparator: Vehicle to NMC<br>Vehicle to nanomedicinal cream (NMC) Twice daily applications | Drug: Investigational Treatment<br>* Topical application for two treatment cycles with twice daily applications, separated by a 4 week treatment pause and followed by 8 week treatment free follow-up.<br>|
| Placebo Comparator: Vehicle to LCC<br>Vehicle to liquid crystal cream (LCC) Twice daily applications | Drug: Investigational Treatment<br>* Topical application for two treatment cycles with twice daily applications, separated by a 4 week treatment pause and followed by 8 week treatment free follow-up.<br>|
| Active Comparator: Aldara<br>Aldara cream 3 applications per week | Drug: Active comparator<br>* Topical treatment with Aldara 3 times per week. The group will be open-label, but however blinded to the efficacy assessor, and followed by 8 week treatment free follow-up.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Number of participants with at least one AE/SAE in the category up to 20 weeks | 20 weeks | 
| Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at 8 Weeks After the End of Treatment (Week 20) for LFX453 Compared to Vehicle Groups Combined | Complete clearance of Actinic keratosis (AK), defined as the number of patients with a count of zero lesions in the treated area, evaluated 8 weeks after the end of treatment (Week 20) for LFX453 compared to vehicle groups combined | Week 20 | 
| Reduction Rate (Percent) of Actinic Keratosis (AK) Lesion Count at 8 Weeks After the End of Treatment (Week 20) for LFX453 Compared to Vehicle Groups Combined | Reduction rate (percent) of Actinic keratosis (AK) lesion count at 8 weeks after the end of treatment (Week 20) for LFX453 compared to vehicle groups combined | Baseline, Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Complete clearance of Actinic keratosis (AK), defined as the number of patients with a count of zero lesions in the treated area, evaluated at week 8 and Week 16 for LFX453 compared to vehicle groups combined | week 8, week 16 | 
| Number of Participants That Had Partial Clearance of Actinic Keratosis (AK) at 8 Weeks After the End of Treatment (Week 20) for LFX453 Compared to Vehicle Groups Combined | Partial clearance of Actinic keratosis (AK), the defined as number of patients with at least 75% reduction in the number of AK lesion count compared to baseline, evaluated at 8 weeks after the end of treatment (Week 20 = EOS visit) for LFX453 compared to vehicle groups combined | Week 20 | 
| Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Partial clearance of Actinic keratosis (AK), the defined as number of patients with at least 75% reduction in the number of AK lesion count compared to baseline, evaluated at week 8 and Week 16 for LFX453 compared to vehicle groups combined | week 8, week 16 | 
| Reduction Rate (Percent) of Actinic Keratosis (AK) Lesion Count at Week 8 for LFX453 Compared to Vehicle Groups Combined | Reduction rate (percent) of Actinic keratosis (AK) lesion count at Week 8 for LFX453 compared to vehicle groups combined | Baseline, Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Actinic keratosis, patients, topical, lesion count, clearance rate