Actinic Keratosis
Conditions
Keywords
topical ointment, skin, hexokinase, precancerous conditions, carcinoma, squamous cell
Brief summary
This Phase 2 clinical trial is a multi-center, randomized, double-blind, placebo-controlled, multiple-dose, parallel-cohort study to assess the efficacy, safety and tolerability of VDA-1102 in the treatment of actinic keratosis (AK) on the head of male and female adult subjects.
Detailed description
Approximately 84 subjects who meet the study's enrollment criteria at the completion of the Screening Period will be randomized to receive 5% or 10% VDA-1102, or matched-placebo. During the Treatment Period, study drug will be applied once-daily for 28 days to a 25 square centimeter area of skin containing 4-8 actinic keratosis lesions on the face or scalp. Subjects will be followed for an additional 28 days (Observation Period) wherein no study drug will be applied. The purpose of the study is to determine whether once-daily application of VDA-1102 ointment for 28 days is effective and well-tolerated in the treatment of actinic keratosis of the face and scalp.
Interventions
DRUGPlacebo
200 mg applied once-daily for 28 days
DRUG5% VDA-1102
200 mg applied once-daily for 28 days
DRUG10% VDA-1102
200 mg applied once-daily for 28 days
Sponsors
Vidac Pharma
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 No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Subject has a minimum of 4 and a maximum of 8 discrete Grade 1-2 AK lesions within a single 25 square centimeter area of skin on their scalp or face Main
Exclusion criteria
* Subject is: (a) pregnant; (b) lactating; (c) planning to become pregnant during the study, or (d) fertile and they or their fertile partner is unable or unwilling to use the required contraceptive methods * Subject is immunosuppressed * Subject has used any of the following topical treatments in the Treatment Field: (1) topical retinoids within 8 weeks of Screening or (2) micro-dermabrasion, laser ablative treatments, ALA-PDT, chemical peels, 5-FU, diclofenac, imiquimod, ingenol, or other topical treatments for AK or that might impact AK within 12 weeks of Screening. * Subject has used systemic retinoid therapy within 6 months of Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Number of Actinic Keratosis Lesions in the Treatment Field on Day 56 | Baseline and day 56 | To compare the reduction on Day 56 in the number of the actinic keratosis (AK) lesions in the Treatment Field of subjects receiving once-daily topical 5% or 10% VDA-1102 ointment for 28 days to the reduction in the number of AK lesions in subjects receiving placebo. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Complete Clearance of Actinic Keratosis Lesions in the Treatment Field | Baseline and Day 56 | The percentage of subjects achieving complete clearance of AK lesions within the Treatment Field on Day 56. |
| Change From Baseline in the Number of AK Lesions Within the Treatment Field of Each Subject on Day 84. | Baseline and day 84 | To compare the reduction on Day 84 in the number of the actinic keratosis lesions |
| AK Grade 2 Lesions Number: Change From Baseline (Day 1 Pre-dose) in Sub-group of Subjects With at Least One Grade 2 Lesion at Baseline (From ITT Population) | Baseline and day 56 | Change from Baseline (Day 1 Pre-dose) in Sub-group of Subjects with at least one Grade 2 Lesion at Baseline (from ITT Population)in the number of grade ≥ 2 lesions. Grade 2 defined as: moderate (moderately thick AK that are easily seen and felt) |
| Change From Baseline in the Adjusted Number of Lesions Weighted by Grade ([Number of Grade 1 Lesions] + [2× Number of Grade 2 Lesions] + [3× Number of Grade 3 Lesions]) | Baseline and day 56 | Change From Baseline in the Adjusted Number of Lesions Weighted by Grade (\[Number of Grade 1 Lesions\] + \[2× Number of Grade 2 Lesions\] + \[3× Number of Grade 3 Lesions\]) Grade 1 - mild (slightly palpable AK that are felt better than seen) Grade 2 - moderate (moderately thick AK that are easily seen and felt) Grade 3 - severe (very thick and/or obvious AK). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Excipeint alone
Placebo: 200 mg applied once-daily for 28 days | 29 |
| 5% VDA-1102 Active study medication
5% VDA-1102: 200 mg applied once-daily for 28 days | 32 |
| 10% VDA-1102 Active study medication
10% VDA-1102: 200 mg applied once-daily for 28 days | 32 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | 5% VDA-1102 | Placebo | 10% VDA-1102 |
|---|---|---|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 9.4 | 67.3 years STANDARD_DEVIATION 8.2 | 65.9 years STANDARD_DEVIATION 7.8 | 66.3 years STANDARD_DEVIATION 11.8 |
| Fitzpatrick skin types III : Light brown skin, burns moderately, tans uniformly | 18 Participants | 9 Participants | 7 Participants | 2 Participants |
| Fitzpatrick skin types II : White skin, usually burns easily, tans minimall | 59 Participants | 18 Participants | 17 Participants | 24 Participants |
| Fitzpatrick skin types I : Pale white skin, always burns, and never tans | 15 Participants | 4 Participants | 5 Participants | 6 Participants |
| Fitzpatrick skin types IV : Moderate brown skin, burns minimally, always tans well. | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — |
| Region of Enrollment Israel | 13 participants | 5 participants | 3 participants | 5 participants |
| Region of Enrollment United States | 80 participants | 27 participants | 26 participants | 27 participants |
| Sex: Female, Male Female | 83 Participants | 28 Participants | 26 Participants | 29 Participants |
| Sex: Female, Male Male | 10 Participants | 4 Participants | 3 Participants | 3 Participants |
| Treatment field location Face | 70 Participants | 24 Participants | 23 Participants | 23 Participants |
| Treatment field location Scalp | 23 Participants | 8 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 3 / 29 | 1 / 32 | 4 / 32 |
| serious Total, serious adverse events | 0 / 29 | 1 / 32 | 1 / 32 |
Outcome results
Primary
Change From Baseline in the Number of Actinic Keratosis Lesions in the Treatment Field on Day 56
To compare the reduction on Day 56 in the number of the actinic keratosis (AK) lesions in the Treatment Field of subjects receiving once-daily topical 5% or 10% VDA-1102 ointment for 28 days to the reduction in the number of AK lesions in subjects receiving placebo.
Time frame: Baseline and day 56
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Number of Actinic Keratosis Lesions in the Treatment Field on Day 56 | -1.54 lesions | Standard Deviation 1.79 |
| 5% VDA-1102 | Change From Baseline in the Number of Actinic Keratosis Lesions in the Treatment Field on Day 56 | -1.34 lesions | Standard Deviation 1.98 |
| 10% VDA-1102 | Change From Baseline in the Number of Actinic Keratosis Lesions in the Treatment Field on Day 56 | -1.94 lesions | Standard Deviation 1.97 |
p-value: 0.9518ANCOVA
p-value: 0.2458ANCOVA
Other Pre-specified
AK Grade 2 Lesions Number: Change From Baseline (Day 1 Pre-dose) in Sub-group of Subjects With at Least One Grade 2 Lesion at Baseline (From ITT Population)
Change from Baseline (Day 1 Pre-dose) in Sub-group of Subjects with at least one Grade 2 Lesion at Baseline (from ITT Population)in the number of grade ≥ 2 lesions. Grade 2 defined as: moderate (moderately thick AK that are easily seen and felt)
Time frame: Baseline and day 56
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AK Grade 2 Lesions Number: Change From Baseline (Day 1 Pre-dose) in Sub-group of Subjects With at Least One Grade 2 Lesion at Baseline (From ITT Population) | -1.20 lesions | Standard Deviation 1.99 |
| 5% VDA-1102 | AK Grade 2 Lesions Number: Change From Baseline (Day 1 Pre-dose) in Sub-group of Subjects With at Least One Grade 2 Lesion at Baseline (From ITT Population) | -1.00 lesions | Standard Deviation 2.08 |
| 10% VDA-1102 | AK Grade 2 Lesions Number: Change From Baseline (Day 1 Pre-dose) in Sub-group of Subjects With at Least One Grade 2 Lesion at Baseline (From ITT Population) | -2.50 lesions | Standard Deviation 2.44 |
p-value: 0.6458ANCOVA
p-value: 0.0721ANCOVA
Other Pre-specified
Change From Baseline in the Adjusted Number of Lesions Weighted by Grade ([Number of Grade 1 Lesions] + [2× Number of Grade 2 Lesions] + [3× Number of Grade 3 Lesions])
Change From Baseline in the Adjusted Number of Lesions Weighted by Grade (\[Number of Grade 1 Lesions\] + \[2× Number of Grade 2 Lesions\] + \[3× Number of Grade 3 Lesions\]) Grade 1 - mild (slightly palpable AK that are felt better than seen) Grade 2 - moderate (moderately thick AK that are easily seen and felt) Grade 3 - severe (very thick and/or obvious AK).
Time frame: Baseline and day 56
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Adjusted Number of Lesions Weighted by Grade ([Number of Grade 1 Lesions] + [2× Number of Grade 2 Lesions] + [3× Number of Grade 3 Lesions]) | -27.8 lesions | Standard Deviation 35.6 |
| 5% VDA-1102 | Change From Baseline in the Adjusted Number of Lesions Weighted by Grade ([Number of Grade 1 Lesions] + [2× Number of Grade 2 Lesions] + [3× Number of Grade 3 Lesions]) | -24.6 lesions | Standard Deviation 40.5 |
| 10% VDA-1102 | Change From Baseline in the Adjusted Number of Lesions Weighted by Grade ([Number of Grade 1 Lesions] + [2× Number of Grade 2 Lesions] + [3× Number of Grade 3 Lesions]) | -38.5 lesions | Standard Deviation 35.3 |
p-value: 0.42ANCOVA
p-value: 0.0241ANCOVA
Other Pre-specified
Change From Baseline in the Number of AK Lesions Within the Treatment Field of Each Subject on Day 84.
To compare the reduction on Day 84 in the number of the actinic keratosis lesions
Time frame: Baseline and day 84
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Number of AK Lesions Within the Treatment Field of Each Subject on Day 84. | -1.64 lesions | Standard Deviation 1.69 |
| 5% VDA-1102 | Change From Baseline in the Number of AK Lesions Within the Treatment Field of Each Subject on Day 84. | -2.05 lesions | Standard Deviation 1.82 |
| 10% VDA-1102 | Change From Baseline in the Number of AK Lesions Within the Treatment Field of Each Subject on Day 84. | -2.15 lesions | Standard Deviation 2.01 |
p-value: 0.2912ANCOVA
p-value: 0.4168ANCOVA
Other Pre-specified
Percentage of Patients With Complete Clearance of Actinic Keratosis Lesions in the Treatment Field
The percentage of subjects achieving complete clearance of AK lesions within the Treatment Field on Day 56.
Time frame: Baseline and Day 56
Population: ITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Patients With Complete Clearance of Actinic Keratosis Lesions in the Treatment Field | 1 Participants |
| 5% VDA-1102 | Percentage of Patients With Complete Clearance of Actinic Keratosis Lesions in the Treatment Field | 3 Participants |
| 10% VDA-1102 | Percentage of Patients With Complete Clearance of Actinic Keratosis Lesions in the Treatment Field | 2 Participants |
p-value: 0.6201Fisher Exact
p-value: 1Fisher Exact