Actinic Keratoses, Squamous Cell Carcinomas
Conditions
Brief summary
The purpose of this trial is to investigate the prevention of actinic keratoses and squamous cell carcinomas by local application of MD-3511356 in comparison to standard sun protection measures in immunosuppressed solid organ transplant recipients.
Detailed description
This open-label multicenter, randomized, inter-individual comparative, prospective clinical trial was designed to evaluate the efficacy and safety of MD 3511356 sunscreen in preventing AK and SCC in post transplant immune-suppressed patients compared to standard of care. The present multicenter trial is intended to contribute to the evidence that daily sun protection will have a prophylactic effect in this high risk population of chronically immune compromised patients.
Interventions
DEVICEMD-3511356
Every morning MD-3511356 should be applied liberally to those skin areas exposed to direct sunlight before exposing to the sun.
OTHERStandard Sun Protection Measures
Self-provided commercially available sunscreen products, corresponding to the dosage recommendations on the product.
Sponsors
Spirig Pharma Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Out-Patients of either sex aged ≥ 40 years * Life-expectancy of 2 years at minimum * Solid organ-transplant recipients who received a kidney (including pancreas), liver, lung, or heart transplant * Patients treated for 5 years with an immunosuppressant medication * Severe sun damage of the skin * Multiple actinic keratoses (2-5 lesions) and/or multiple dysplastic naevi * No present squamous cell carcinoma, basal cell carcinoma or malignant melanoma; but history of cutaneous/cutaneous invasive malignancy with restitutio ad integrum is allowed * Patients who are able to understand and provide written informed consent to participate in the clinical trial (signed informed consent) according to ICH GCP
Exclusion criteria
* Non-Caucasian * Absence of sun damage i.e. no signs of AK * Multi-organ transplantation (exception: simultaneous transplantation of kidney and pancreas) * Evidence of systemic infection, except viral hepatitis, at the time of recruitment * Known or supposed systemic malignant tumour or systemic chemotherapy within the last 5 years prior to randomisation * Patients participating in a clinical trial within the last four weeks before trial * Patients treated with the antitumour/antiangiogenetic immunosuppressant sirolimus, respectively everolimus, or acitretin or any other systemic treatment for AK at the time of randomisation * Patients treated with a topical drug for the AK at the time of randomisation (exception: excision or Cryotherapy for hyperkeratotic lesions are allowed) * Change of the immunosuppression-treatment less than 3 months ago or planned * Present or planned interferon therapy (in liver transplant patients with hepatitis B/C) * Female patients with childbearing potential with a positive pregnancy test, breast feeding, or female patients with childbearing potential without adequate contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of New Clinically Diagnosed Actinic Keratoses or Squamous Cell Carcinomas | 2 Years |
Secondary
| Measure | Time frame |
|---|---|
| Number of Patients With New Actinic Keratoses, Squamous Cell Carcinomas or Basal Cell Carcinomas | 2 Years |
Countries
Austria, Czechia, France, Germany, Ireland, Netherlands, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
Of 244 patients enrolled, 3 patients were considered screening failures (003-006, 005-002 and 010-027). Patient 003 006 used forbidden concomitant medication. Patient 005 002 had severe sun damage of the skin, violation of exclusion criterion #5. Patient 010 027 was re-enrolled as Patient 010 029 and later randomized to the MD-3511356 group.
Pre-assignment details
Of 244 patients enrolled, 3 patients were considered screening failures (003-006, 005-002 and 010-027). Patient 003 006 used forbidden concomitant medication. Patient 005 002 had severe sun damage of the skin, violation of exclusion criterion #5. Patient 010 027 was re-enrolled as Patient 010 029 and later randomized to the MD-3511356 group.
Participants by arm
| Arm | Count |
|---|---|
| Standard Sun Protection Measures Standard Sun Protection Measures: Self-provided commercially available sunscreen products, corresponding to the dosage recommendations on the product. | 81 |
| MD-3511356 MD-3511356: Every morning MD-3511356 should be applied liberally to those skin areas exposed to direct sunlight before exposing to the sun. | 160 |
| Total | 241 |
Baseline characteristics
| Characteristic | Standard Sun Protection Measures | MD-3511356 | Total |
|---|---|---|---|
| Age, Continuous | 63.20 years STANDARD_DEVIATION 9.483 | 62.29 years STANDARD_DEVIATION 8.875 | 62.59 years STANDARD_DEVIATION 9.075 |
| Sex: Female, Male Female | 16 Participants | 45 Participants | 61 Participants |
| Sex: Female, Male Male | 65 Participants | 115 Participants | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 81 | 11 / 160 |
| serious Total, serious adverse events | 29 / 81 | 38 / 160 |
Outcome results
Primary
Number of New Clinically Diagnosed Actinic Keratoses or Squamous Cell Carcinomas
Time frame: 2 Years
Population: 241 patients were randomized: 160 to the MD 3511356 group and 81 to the standard care group. All 241 randomized patients received at least one dose of trial device and therefore were all included in the safety population. The Full analysis set (FAS) comprised 220 patients: 146 in the MD 3511356 group and 74 in the standard care group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Sun Protection Measures | Number of New Clinically Diagnosed Actinic Keratoses or Squamous Cell Carcinomas | 11.73 new actinic keratoses or scc | Standard Deviation 14.939 |
| MD-3511356 | Number of New Clinically Diagnosed Actinic Keratoses or Squamous Cell Carcinomas | 9.88 new actinic keratoses or scc | Standard Deviation 15.761 |
p-value: 0.0278ANCOVA
Secondary
Number of Patients With New Actinic Keratoses, Squamous Cell Carcinomas or Basal Cell Carcinomas
Time frame: 2 Years
Population: The Full analysis set (FAS) comprised 220 patients: 146 in the MD 3511356 group and 74 in the standard care group.~For patient 10018 (MD-3511356 group) the age of first organ transplant was not computable due to missing date.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Sun Protection Measures | Number of Patients With New Actinic Keratoses, Squamous Cell Carcinomas or Basal Cell Carcinomas | 83.8 percentage of patients |
| MD-3511356 | Number of Patients With New Actinic Keratoses, Squamous Cell Carcinomas or Basal Cell Carcinomas | 77.2 percentage of patients |
p-value: <0.0595% CI: [0.2703, 1.2405]ANCOVA