Actinic Keratosis
Conditions
Keywords
Actinic Keratosis, lung transplant, kidney transplant
Brief summary
This is a single arm, open-label interventional study of ingenol mebutate 0.015% in solid organ transplant recipients. The investigators plan to treat 20 subjects, 10 kidney transplant recipients and 10 lung transplant recipients. The investigators have selected these two populations as the represent the spectrum of solid organ transplantation: kidney transplant recipients are the largest transplant population, but have lower levels of immunosuppression and skin cancer risk. Lung transplant recipients have the highest burden of skin cancer and actinic keratoses.
Detailed description
Actinic keratoses (AK) are patches of dysplastic keratinocytes arising in sun-damaged skin. These lesions are precursors to cutaneous squamous cell carcinoma (SCC), and are treated to prevent progression to SCC. First-line therapy for AK include cryotherapy and curettage, which target clinically visible lesions but do not address the subclinical lesions in the field of ultraviolet radiation damage. Field therapy includes topical chemotherapy, immunotherapy, and photodynamic therapy. Ingenol mebutate is the active compound found in Euphorbia peplus sap, and has been approved for treatment of AK in immunocompetent patients. Ingenol mebutate 0.015% is favored over other topical treatments for treatment of AK on the face due to the brief treatment course, high clearance rate, and resolution without sequelae. Solid organ transplant recipients (OTR) have a high incidence of AK and high risk of developing SCC, and require frequent field therapy. In addition, OTR generally have a higher burden of AK and require treatment of a larger surface area than the 25 cm2 area labeled for ingenol mebutate 0.015%. The investigators plan to investigate the safety and efficacy of ingenol mebutate 0.015% in OTR, with a treatment area up to 100cm2. This is a single arm, open-label interventional study of ingenol mebutate 0.015% in solid organ transplant recipients. The investigators plan to treat 20 subjects, 10 kidney transplant recipients and 10 lung transplant recipients. The investigators have selected these two populations as the represent the spectrum of solid organ transplantation: kidney transplant recipients are the largest transplant population, but have lower levels of immunosuppression and skin cancer risk. Lung transplant recipients have the highest burden of skin cancer and actinic keratoses.
Interventions
ingenol mebutate gel 0.015% to be applied on treatment area
Sponsors
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults at least 18 years old. 2. Subject must be a solid organ transplant recipient at least one year from the date of transplantation. 3. Subjects must be in stable health as confirmed by medical history, per investigator judgement. 4. Subjects must be able to read, sign, and understand the informed consent. 5. Subjects have at least 4 and no more than 20 clinically typical (non-hyperkeratotic/hypertrophic), visible actinic keratoses in a treatment area of approximately 100cm2 on the face. Treatment areas will include a single cheek (nasofacial sulcus to tragus, malar cheekbone to jawline and avoiding the lower eyelid and mouth); the forehead (hairline to eyebrows, extending laterally to the root of the helix). 6. Subject must be willing to forego any other treatments on the face, including cryotherapy, tanning bed use and excessive sun exposure while in the study. 7. Subject is willing and able to participate in the study and to comply with all study requirements including concomitant medication and other treatment restrictions. 8. If subject is a female of childbearing potential she must have a negative urine pregnancy test result prior to study treatment initiation and must agree to use an approved method of birth control while enrolled in the study.
Exclusion criteria
1. Subjects with an unstable medical condition as deemed by the clinical investigator. 2. Subjects with a history of bone marrow or stem cell transplantation. 3. Subjects with non-melanoma skin cancer on the face. 4. Subjects with hyperkeratotic or hypertrophic AKs. 5. Subjects with any dermatologic disease in the treatment area that may be exacerbated by the treatment proposed or that might impair the evaluation of AKs. 6. Women who are pregnant, lactating, or planning to become pregnant during the study period. 7. Subjects who have previously been treated with ingenol mebutate in study area within the past 8 weeks. 8. Subjects who have used any topical prescription medications for actinic keratosis on the study area within 8 weeks prior to study treatment initiation. 9. Subjects who have used any topical prescription medications for other reason on the study area within 4 weeks prior to study treatment initiation. 10. Subjects who are currently participating in another clinical study or have completed another clinical study with an investigational drug or device on the study area within 30 days prior to study treatment initiation. 11. Subjects with known hypersensitivity to Picato gel or any of the inactive ingredients: isopropyl alcohol, hydroxyethyl cellulose, citric acid monohydrate, sodium citrate, or benzyl alcohol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From screening to Day 57 or study early termination if applicable | To evaluate the safety of ingenol mebutate gel 0.015% on the face in solid organ transplant recipients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Reduction of Actinic Keratosis | Day 57 (assessed at screening, day 1, day 29, day 57, and study early termination if applicable, clearance at day 57 reported) | To evaluate the efficacy of ingenol mebutate for reduction of actinic keratoses on the face in organ transplant recipients. |
| Participant's Local Skin Response Grading Scale | Day 1, Day 4 (assessed at screening, day 1, day 4, day 29, day 57, and study early termination if applicable, results at day 1 and day 4 reported) | To investigate the local skin response to ingenol mebutate in organ transplant recipients. Local skin reaction (LSR) will be graded by visual assessment on a 4 point scale where 0=none, 1=mild, 2=moderate, 3=severe. Each of the following four reactions will be graded: erythema, vesiculation/postulation, crusting/scabbing/erosion, and edema/swelling. A composite score will be calculated (range 0-16). A high LSR indicated a worse outcome. LSR assessment will be performed at days 1, 8, 29, and 84. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label Treatment All patients will be treated with ingenol mebutate gel 0.015%. There is no placebo or comparator for this study. The investigator will identify the patient's treatment area at Baseline, and provide a detailed application instruction sheet. The first dose will be applied in clinic under the supervision of the investigator.
ingenol mebutate gel 0.015%: ingenol mebutate gel 0.015% to be applied on treatment area | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Open Label Treatment |
|---|---|
| Age, Continuous | 65.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Organ Transplant Type Kidney | 7 Participants |
| Organ Transplant Type Kidney/Heart | 1 Participants |
| Organ Transplant Type Kidney/Liver | 1 Participants |
| Organ Transplant Type Kidney/Pancreas | 2 Participants |
| Organ Transplant Type Lung | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 14 Participants |
| Years Since Transplant | 10.9 years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 10 / 20 |
| serious Total, serious adverse events | 5 / 20 |
Outcome results
Primary
Number of Participants With Adverse Events
To evaluate the safety of ingenol mebutate gel 0.015% on the face in solid organ transplant recipients
Time frame: From screening to Day 57 or study early termination if applicable
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open Label Treatment | Number of Participants With Adverse Events | Facial edema | 12 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Pain in Treatment Area | 11 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Pruritus | 6 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Headache | 3 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Squamous Cell Carcinoma Outside Treatment Area | 3 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Diarrhea | 2 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Xerosis | 2 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Urosepsis | 1 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Worsening of CKD | 3 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Hyperglycemia | 2 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Acute Kidney Injury | 1 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Hyperkalemia | 1 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Anemia | 1 Participants |
| Open Label Treatment | Number of Participants With Adverse Events | Hypertriglyceridemia | 1 Participants |
Secondary
Number of Participants With a Reduction of Actinic Keratosis
To evaluate the efficacy of ingenol mebutate for reduction of actinic keratoses on the face in organ transplant recipients.
Time frame: Day 57 (assessed at screening, day 1, day 29, day 57, and study early termination if applicable, clearance at day 57 reported)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open Label Treatment | Number of Participants With a Reduction of Actinic Keratosis | 75% Clearance of Actinic Keratoses at Day 57 | 12 Participants |
| Open Label Treatment | Number of Participants With a Reduction of Actinic Keratosis | 100% Clearance of Actinic Keratoses at Day 57 | 8 Participants |
Secondary
Participant's Local Skin Response Grading Scale
To investigate the local skin response to ingenol mebutate in organ transplant recipients. Local skin reaction (LSR) will be graded by visual assessment on a 4 point scale where 0=none, 1=mild, 2=moderate, 3=severe. Each of the following four reactions will be graded: erythema, vesiculation/postulation, crusting/scabbing/erosion, and edema/swelling. A composite score will be calculated (range 0-16). A high LSR indicated a worse outcome. LSR assessment will be performed at days 1, 8, 29, and 84.
Time frame: Day 1, Day 4 (assessed at screening, day 1, day 4, day 29, day 57, and study early termination if applicable, results at day 1 and day 4 reported)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Treatment | Participant's Local Skin Response Grading Scale | Baseline Local Skin Reaction Composite Score | 1.2 score on a scale | Standard Deviation 0.8 |
| Open Label Treatment | Participant's Local Skin Response Grading Scale | Day 4 Local Skin Reaction Composite Score | 11.7 score on a scale | Standard Deviation 4.2 |