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

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

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.

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: Investigational Treatment; Drug: Active comparator

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1040
    • Novartis Investigative Site
• Denmark
  • Copenhagen NV, Denmark, DK-2400
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Berlin, Germany, 10098
    • Novartis Investigative Site
  • Bonn, Germany, 53111
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Hamburg, Germany, 20354
    • Novartis Investigative Site
• Iceland
  • Kopavogur, Iceland, 201
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, E1 1BB
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LFX453 0.1% NMC; LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications	Drug: Investigational Treatment; 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.
Experimental: LFX453 0.15% LCC; LFX453 0.15% liquid crystal cream (LCC) Twice daily applications	Drug: Investigational Treatment; 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.
Placebo Comparator: Vehicle to NMC; Vehicle to nanomedicinal cream (NMC) Twice daily applications	Drug: Investigational Treatment; 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.
Placebo Comparator: Vehicle to LCC; Vehicle to liquid crystal cream (LCC) Twice daily applications	Drug: Investigational Treatment; 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.
Active Comparator: Aldara; Aldara cream 3 applications per week	Drug: Active comparator; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2015
• Primary Completion (Actual): January 27, 2016
• Study Completion (Actual): January 27, 2016

Study Registration Dates

• First Submitted: January 23, 2015
• First Submitted That Met QC Criteria: March 30, 2015
• First Posted (Estimate): March 31, 2015

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Actinic keratosis, patients, topical, lesion count, clearance rate
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Other Study ID Numbers: CLFX453X2201