Actinic Keratosis
Conditions
Keywords
Actinic keratosis, patients, topical, lesion count, clearance rate
Brief summary
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.
Interventions
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.
DRUGActive 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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | 20 weeks | Number of participants with at least one AE/SAE in the category up to 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 | Week 20 | 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 |
| 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | week 8, week 16 | 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 |
| Reduction Rate (Percent) of Actinic Keratosis (AK) Lesion Count at Week 8 for LFX453 Compared to Vehicle Groups Combined | Baseline, Week 8 | Reduction rate (percent) of Actinic keratosis (AK) lesion count at Week 8 for LFX453 compared to vehicle groups combined |
| 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 | Week 20 | 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 |
| Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | week 8, week 16 | 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 |
Countries
Austria, Denmark, Germany, Iceland, United Kingdom
Participant flow
Recruitment details
A total of 82 patients, male and female of non-childbearing potential aged 18-75 years, with Actinic Keratosis (AK) on the face or balding scalp were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| LFX453 0.1% NMC LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications | 20 |
| LFX453 0.15% LCC LFX453 0.15% liquid crystal cream (LCC) Twice daily applications | 20 |
| Vehicle to NMC Vehicle to nanomedicinal cream (NMC) Twice daily applications | 11 |
| Vehicle to LCC Vehicle to liquid crystal cream (LCC) Twice daily applications | 10 |
| Aldara Aldara cream 3 applications per week | 21 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 0 | 2 |
| Overall Study | Subject/guardian decision | 1 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | LFX453 0.1% NMC | LFX453 0.15% LCC | Vehicle to NMC | Vehicle to LCC | Aldara | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 67.7 years STANDARD_DEVIATION 5.23 | 68.6 years STANDARD_DEVIATION 6.25 | 68.3 years STANDARD_DEVIATION 6.66 | 70.2 years STANDARD_DEVIATION 4.32 | 68.6 years STANDARD_DEVIATION 5.61 | 68.5 years STANDARD_DEVIATION 5.61 |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 9 Participants |
| Sex: Female, Male Male | 15 Participants | 18 Participants | 11 Participants | 8 Participants | 21 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 20 | 14 / 20 | 9 / 11 | 8 / 10 | 17 / 21 |
| serious Total, serious adverse events | 1 / 20 | 1 / 20 | 1 / 11 | 1 / 10 | 1 / 21 |
Outcome results
Primary
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
Time frame: 20 weeks
Population: The safety analysis set included all patients that received any study drug. For Safety \& Tolerability only the 2 vehicles have separate analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LFX453 0.1% NMC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Adverse Events (AEs) | 10 participants |
| LFX453 0.1% NMC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Serious Adverse Events (SAEs) | 1 participants |
| LFX453 0.15% LCC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Adverse Events (AEs) | 15 participants |
| LFX453 0.15% LCC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Serious Adverse Events (SAEs) | 1 participants |
| Vehicle to NMC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Adverse Events (AEs) | 9 participants |
| Vehicle to NMC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Serious Adverse Events (SAEs) | 1 participants |
| Vehicle to LCC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Serious Adverse Events (SAEs) | 1 participants |
| Vehicle to LCC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Adverse Events (AEs) | 8 participants |
| Aldara | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Adverse Events (AEs) | 18 participants |
| Aldara | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 20 Weeks | Serious Adverse Events (SAEs) | 1 participants |
Primary
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
Time frame: Week 20
Population: Pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. For efficacy end points only there were combined analysis of the 2 vehicle groups. Vehicle groups were analyzed separately for safety and tolerability only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LFX453 0.1% NMC | 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 | 1 participants |
| LFX453 0.15% LCC | 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 | 1 participants |
| Vehicle to NMC | 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 | 1 participants |
| Vehicle to LCC | 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 | 13 participants |
p-value: 0.51590% CI: [-0.12, 0.12]Posterior mean
p-value: 0.51790% CI: [-0.12, 0.13]posterior mean
Primary
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
Time frame: Baseline, Week 20
Population: Pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. For efficacy end points only there were combined analysis of the 2 vehicle groups. Vehicle groups were analyzed separately for safety and tolerability only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFX453 0.1% NMC | 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 | 33.2 percent change | Standard Deviation 31.19 |
| LFX453 0.15% LCC | 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 | 34.5 percent change | Standard Deviation 33.2 |
| Vehicle to NMC | 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 | 34.3 percent change | Standard Deviation 33.31 |
| Vehicle to LCC | 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 | 86.7 percent change | Standard Deviation 23.53 |
Secondary
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
Time frame: week 8, week 16
Population: Pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. For efficacy end points only there were combined analysis of the 2 vehicle groups. Vehicle groups were analyzed separately for safety and tolerability only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LFX453 0.1% NMC | Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 8 | 0 participants |
| LFX453 0.1% NMC | Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 16 | 1 participants |
| LFX453 0.15% LCC | Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 16 | 1 participants |
| LFX453 0.15% LCC | Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 8 | 0 participants |
| Vehicle to NMC | Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 8 | 1 participants |
| Vehicle to NMC | Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 16 | 1 participants |
| Vehicle to LCC | Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 8 | 3 participants |
| Vehicle to LCC | Number of Participants That Had Complete Clearance of Actinic Keratosis (AK) at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 16 | 9 participants |
Secondary
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
Time frame: Week 20
Population: Pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. For efficacy end points only there were combined analysis of the 2 vehicle groups. Vehicle groups were analyzed separately for safety and tolerability only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LFX453 0.1% NMC | 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 | 1 participants |
| LFX453 0.15% LCC | 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 | 2 participants |
| Vehicle to NMC | 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 | 2 participants |
| Vehicle to LCC | 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 | 16 participants |
Secondary
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
Time frame: week 8, week 16
Population: Pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. For efficacy end points only there were combined analysis of the 2 vehicle groups. Vehicle groups were analyzed separately for safety and tolerability only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LFX453 0.1% NMC | Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 8 | 1 participants |
| LFX453 0.1% NMC | Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 16 | 3 participants |
| LFX453 0.15% LCC | Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 16 | 4 participants |
| LFX453 0.15% LCC | Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 8 | 0 participants |
| Vehicle to NMC | Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 8 | 3 participants |
| Vehicle to NMC | Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 16 | 3 participants |
| Vehicle to LCC | Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 8 | 7 participants |
| Vehicle to LCC | Number of Participants That Partial Clearance of Actinic Keratosis (AK) at at Week 8 and Week 16 for LFX453 Compared to Vehicle Groups Combined | Week 16 | 15 participants |
Secondary
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
Time frame: Baseline, Week 8
Population: Pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. For efficacy end points only there were combined analysis of the 2 vehicle groups. Vehicle groups were analyzed separately for safety and tolerability only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFX453 0.1% NMC | Reduction Rate (Percent) of Actinic Keratosis (AK) Lesion Count at Week 8 for LFX453 Compared to Vehicle Groups Combined | 21.9 percent change | Standard Deviation 36.18 |
| LFX453 0.15% LCC | Reduction Rate (Percent) of Actinic Keratosis (AK) Lesion Count at Week 8 for LFX453 Compared to Vehicle Groups Combined | 21.9 percent change | Standard Deviation 28.91 |
| Vehicle to NMC | Reduction Rate (Percent) of Actinic Keratosis (AK) Lesion Count at Week 8 for LFX453 Compared to Vehicle Groups Combined | 32.3 percent change | Standard Deviation 33.55 |
| Vehicle to LCC | Reduction Rate (Percent) of Actinic Keratosis (AK) Lesion Count at Week 8 for LFX453 Compared to Vehicle Groups Combined | 55.8 percent change | Standard Deviation 36.54 |