CompletedNCT02866695Updated Mar 9, 2022Results posted

Safety and Efficacy of Ingenol Mebutate Gel 0.015% for Treatment of AK on the Face in Solid Organ Transplant Recipients

A Phase 4 interventional study of ingenol mebutate gel 0.015% in Actinic Keratosis, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-03-09.

Sponsored by University of California, San Francisco · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 20
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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.

Conditions studied

Actinic Keratosis

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Keywords

Actinic Keratosis
lung transplant
kidney transplant

In context

Keratosis, Actinic

364 studies on the registry are indexed under Keratosis, Actinic; 31 are open to participants now.

This study's enrollment of 20 is below the median of 60 across 315 interventional studies indexed under Keratosis, Actinic.

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Lead sponsor

University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.

Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Adults at least 18 years old.
Subject must be a solid organ transplant recipient at least one year from the date of transplantation.
Subjects must be in stable health as confirmed by medical history, per investigator judgement.
Subjects must be able to read, sign, and understand the informed consent.
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).
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.
Subject is willing and able to participate in the study and to comply with all study requirements including concomitant medication and other treatment restrictions.
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

Exclusion Criteria:

Subjects with an unstable medical condition as deemed by the clinical investigator.
Subjects with a history of bone marrow or stem cell transplantation.
Subjects with non-melanoma skin cancer on the face.
Subjects with hyperkeratotic or hypertrophic AKs.
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.
Women who are pregnant, lactating, or planning to become pregnant during the study period.
Subjects who have previously been treated with ingenol mebutate in study area within the past 8 weeks.
Subjects who have used any topical prescription medications for actinic keratosis on the study area within 8 weeks prior to study treatment initiation.
Subjects who have used any topical prescription medications for other reason on the study area within 4 weeks prior to study treatment initiation.
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.
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.

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 20 participants (actual)

Study arms

Other
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.
Drug: ingenol mebutate gel 0.015%

Interventions

Drugingenol mebutate gel 0.015%
ingenol mebutate gel 0.015% to be applied on treatment area
Also known as: Picato

What researchers measure

Primary outcomes

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

Secondary outcomes

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)
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)

Results

Posted Feb 25, 2019

Participant flow

Participant flow — Overall Study
Milestone	Open Label Treatment
Started	20
Completed	18
Not completed	2
Withdrew: Adverse event	1
Withdrew: Lost to follow-up	1

Outcome measures

PrimaryNumber 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
Reported as:: Count of participants · Participants

Number of Participants With Adverse Events
Participants	Open Label Treatment
Facial edema	12
Pain in Treatment Area	11
Pruritus	6
Headache	3
Squamous Cell Carcinoma Outside Treatment Area	3
Diarrhea	2
Xerosis	2
Urosepsis	1
Worsening of CKD	3
Hyperglycemia	2
Acute Kidney Injury	1
Hyperkalemia	1
Anemia	1
Hypertriglyceridemia	1

SecondaryNumber 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)
Reported as:: Count of participants · Participants

Number of Participants With a Reduction of Actinic Keratosis
Participants	Open Label Treatment
75% Clearance of Actinic Keratoses at Day 57	12
100% Clearance of Actinic Keratoses at Day 57	8

SecondaryParticipant'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)
Reported as:: Mean · score on a scale

Participant's Local Skin Response Grading Scale
score on a scale	Open Label Treatment
Baseline Local Skin Reaction Composite Score	1.2 ± 0.8
Day 4 Local Skin Reaction Composite Score	11.7 ± 4.2

Adverse events

Collected over Each participant was assessed for 57 days from the start of treatment.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Open Label Treatment	0/20 (0%)	5/20 (25%)	10/20 (50%)

Most frequent serious events

Most frequent serious events
Event	Open Label Treatment
UrosepsisRenal and urinary disorders	1/20
DiarrheaGastrointestinal disorders	1/20
Chronic Kidney DiseaseRenal and urinary disorders	1/20
AnemiaBlood and lymphatic system disorders	1/20
HypertriglyceridemiaMetabolism and nutrition disorders	1/20

Most frequent other events

Most frequent other events
Event	Open Label Treatment
Acute Kidney InjuryRenal and urinary disorders	4/20
HyperglycemiaMetabolism and nutrition disorders	2/20
HyponatremiaRenal and urinary disorders	2/20
HypoalbuminemiaRenal and urinary disorders	2/20
HyperkalemiaRenal and urinary disorders	1/20
HypocalcemiaRenal and urinary disorders	1/20
NeutropeniaBlood and lymphatic system disorders	1/20

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Open Label Treatment
Mean	65.3 (42.1 to 75.2)

Sex: Female, Male
Sex: Female, Male(Participants)	Open Label Treatment
Female	6
Male	14

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Open Label Treatment
Hispanic or Latino	1
Not Hispanic or Latino	19
Unknown or Not Reported	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Open Label Treatment
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	20
More than one race	0
Unknown or Not Reported	0

Region of Enrollment
Region of Enrollment(participants)	Open Label Treatment
United States	20

Organ Transplant Type
Organ Transplant Type(Participants)	Open Label Treatment
Lung	9
Kidney	7
Kidney/Pancreas	2
Kidney/Liver	1
Kidney/Heart	1

Years Since Transplant
Years Since Transplant(years)	Open Label Treatment
Mean	10.9 (1 to 33)

Study locations

1 site

UCSF Dermatology
San Francisco, California 94115, United States

References and documents

Study documents

Protocol and statistical analysis plan · Oct 18, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Individual participant data may be shared with authorized representatives of the study sponsor LEO Pharma, Inc., The University of California, FDA

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 9, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02866695
Lead sponsor: University of California, San Francisco
Responsible party: Sponsor
First posted: Aug 15, 2016
Start date: Oct 6, 2016
Primary completion: Jul 2, 2018
Completion: Jul 2, 2018
Results posted: Feb 25, 2019
Last update: Mar 9, 2022

Study contacts

Sarah Arron, MD, PhD

principal investigator · University of California, San Francisco

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.

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