Actinic Keratosis MedDRA version: 16.1 Level: PT Classification code 10000614 Term: Actinic keratosis System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Interventions
Product Name: Resiquimod Gel
Pharmaceutical Form: Gel
INN or Proposed INN: Resiquimod
CAS Number: 144875-48-9
Current Sponsor code: R-848
Other descriptive name: S-28463, VML600
Concentration unit: %
Sponsors
Spirig Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed informed consent • Male or nonpregnant, nonlactating female, =18 years. For women of childbearing potential the use of highly effective methods of birth control (precautions to prevent pregnancy) is mandatory. Highly effective methods of birth control are defined as those, alone or in combination, which result in a low failure rate (i.e. less than 1 % per year) when used consistently and correctly - such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. In this trial women of childbearing potential are instructed to use oral contraceptives or IUDs in combination with a barrier device (e.g. condom). • A minimum of 2 clinically diagnosed AK-lesions within a 25 cm2 contiguous treatment area (balding scalp, forehead, face). One AK-lesion must have a diameter of at least 6 mm (indicator lesion).The patient may have been treated in the past for AK-lesions. But for the existing AK-lesions the restrictions for treatments before the start of the trial must be observed (see below exclusion criteria). • Free of other significant findings in the treatment field that could impair examination of the treatment or surrounding area (defined as the area within a 5 cm margin of the treatment area in all directions). • Willing and able to participate in the trial as an outpatient and comply with all trial requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Evidence of unstable or uncontrolled clinically significant medical conditions as determined by the investigator (e.g., cardiovascular, immunosuppressive, hematologic, hepatic, neurologic, renal, endocrine, collagen-vascular, gastrointestinal abnormalities or diseases). • Evidence of an active infection. • Evidence of immunosuppression or systemic cancer. • Known autoimmune disorder (especially psoriasis), impaired immune system (e.g. HIV), known thyroid abnormalities, known depression. • Dermatological disease or condition in the treatment or surrounding area that might be exacerbated by treatment with resiquimod gel or may impair trial assessments (e.g., rosacea, atopic dermatitis, eczema) as assessed by the investigator. • Current alcohol abuse or chemical dependency as assessed by the investigator. • Participation in another clinical trial within one month of trial entry. • Known allergy or hypersensitivity to any of the trial gel ingredients. • Pretreatments for the existing AK-lesions are restricted before the start of the trial, in the sense that different periods of grace must be observed: • Local/topical treatments in the treatment area • Dermabrasion, chemical peeling, laser treatment, cryotherapy or surgery within 6 weeks of trial entry • Imiquimod, diclofenac, 5-Fluorouracil (5-FU), topical corticosteroids, topical retinoids, treatment of the head with ultraviolet B (UVB) or photodynamic treatment (PDT) within 6 weeks of trial entry • Systemic treatments • High-dose vitamin A (>15’000 units per day) within 2 weeks of trial entry • Interferon/ interferon-inducers, immunosuppressors, immunomodulatory medicinal products, systemic (>10 mg/day) or high-dosed inhaled (>1600 µg/day) corticosteroids within 4 weeks of trial entry • Chemotherapy or systemic retinoids within 6 months of trial entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to define the concentration and dosage schedule of resiquimod gel at which complete clearance (no AK-lesion according to clinical inspection in a treated 25 cm2 area) occurs (Treatment Arms 1, 2, 3), or at which a biological endpoint (clinical manifestation of skin erosion, that is the skin appears reddened, erosive and weeping) is achieved with subsequent complete clearance (Treatment Arms 4 and 5).;Secondary Objective: Secondary objectives relate to the efficacy, local tolerability and the safety of the various concentrations and dosage schedules of resiquimod gel in terms of • complete clinical clearance in the treated 25 cm2 field at starting point of second treatment cycle • partial clearance (disappearance of =75% of AK-lesions in the treated 25 cm2 area) at the end of trial • complete clearance of the entire treatment field (=25 cm2 area), verified by confocal microscopy at the end of trial (optional, at specific centers) • histological proof of clearance of an indicator lesion at the end of trial • global judgment of efficacy and tolerability by the investigator and the patient based on point scores at the starting point of the second treatment cycle (Treatment Arms 1, 2, 3) and at the end of the trial (all Treatment Arms) • number of patients withdrawn from trial • quality of life (QoL) assessment • number of adverse and serious adverse events;Primary end point(s): • Number of patients with complete clinical clearance (no AK-lesion according to clinical inspection in the treated 25 cm2 area) at the end of trial. • Number of patients with complete clinical clearance after reaching a biological endpoint (manifestation of skin erosion, i.e., reddened, erosive and weeping skin) plus 8 weeks follow-up (in Treatment Arms 4 and 5).;Timepoint(s) of evaluation of this end point: • At the end of trial. • After reaching a biological endpoint (manifestation of skin erosion, i.e., reddened, erosive and weeping skin) plus 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: • Start of second treatment cycle (Arms 1-3): - No. of patients (pts) with complete clinical clearance in treated area - Global judgment of efficacy and tolerability by investigator and pts • End of trial: - No. of pts with partial clearance (disappearance of =75%) of AK-lesions in treated area - No. of pts with clearance of entire treatment field, verified by confocal microscopy (optional) - No. of pts with histological proof of clearance of indicator lesion - Global judgment of efficacy and tolerability by investigator and pts QoL assessments • Visit 2 (all Arms) Visit 3 (Arms 1-3) or after reaching biological endpoint (Arms 4, 5): - QoL assessments • Ongoing: - Evaluation of AEs and SAEs, local and systemic tolerability and pts compliance - No. of pts withdrawn;Secondary end point(s): Efficacy • Number of patients with complete clinical clearance (clinical inspection) in the treated 25 cm2 area at starting point of the second treatment cycle (Treatment Arms 1-3). • Number of patients with partial clearance (disappearance of =75%) of AK-lesions (clinical inspection) in the treated 25 cm2 area at the end of trial. • Number of patients with clearance of the entire treatment field, verified by confocal microscopy (optional, at specific centers) at the end of trial. • Number of patients with histological proof of clearance of the indicator lesion at the end of trial. • Global judgment of efficacy by investigator and patient by means of point scores at the starting point of the second treatment cycle (Treatment Arms 1, 2, 3) and at the end of trial (all Treatment Arms). • QoL assessments (by means of Skindex-29) at Day 1 (Visit 2), after the first treatment period (Visit 3) in the Treatment Arms 1, 2 and 3, or after reaching the biological endpoint (skin erosion) in the Treatment Arms 4 and 5, and at the end of the trial (all Treatment Arms) Safety • Evaluation of adverse events (AEs) and serious adverse events (SAEs). • Ev | — |
Countries
Germany, Switzerland
Outcome results
None listed