Safety and Efficacy of Ingenol Mebutate 0.05% Gel When Used After Cryotherapy in the Hypertrophic Actinic Keratoses

• ClinicalTrials.gov Identifier: NCT02251652
• Recruitment Status: Completed
• First Posted: September 29, 2014
• Results First Posted: April 26, 2017
• Last Update Posted: April 26, 2017
• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborator: LEO Pharma
• Information provided by (Responsible Party): Gary Goldenberg, Icahn School of Medicine at Mount Sinai

Study Description

Brief Summary:

Sequential therapy with cryosurgery and ingenol mebutate may optimize the treatment of hypertrophic AKs and also treat non-hypertrophic AKs in this anatomic location. Furthermore, use of ingenol mebutate will also be evaluated for potential treatment of subclinical lesions.

Condition or disease	Intervention/treatment	Phase
Actinic Keratoses	Drug: Ingenol Mebutate; Procedure: Cryotherapy	Phase 4

Detailed Description:

The investigators plan to treat 30 subjects. Each qualifying subject will have at least 3 hypertrophic AKs, defined as more than 3mm in thickness, on each dorsal hand. Cryotherapy will be standardized in all patients and for all treated lesions: 1-2 sprays, 5 seconds each, with a 5 second interval. All subjects will be treated with the same cryo-spray. Following cryotherapy, subjects will be randomized to treat either their right or left dorsal hand with ingenol mebutate gel. The decision to treat the right vs. the left hand will be chosen by chance, like flipping a coin. Neither the subject nor the study doctor will choose what arm receives the ingenol mebutate gel. The study doctor will not know which arm is treated with ingenol mebutate, so the subject should not reveal that information to him or her at any time during the study. Subjects will treat the randomized dorsal hand with ingenol mebutate 0.05% gel starting on the same day as the cryotherapy (Day 0). Subjects will utilize the once daily for two days regimen. Subjects will be followed on day 4 after their initial visit, day 8, day 15, day 29, and day 57, with a two day window period.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Investigator-Initiated Study to Assess the Safety and Efficacy of Ingenol Mebutate 0.05% Gel When Used After Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses (AK) on Dorsal Hands
• Study Start Date: April 2013
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Combination Therapy; Cryotherapy followed by Ingenol Mebutate Gel	Drug: Ingenol Mebutate; Ingenol mebutate 0.05% gel; Other Name: PEP005 Gel; Procedure: Cryotherapy; 1-2 sprays, 5 seconds each, with a 5 second interval
Active Comparator: Cryotherapy Alone; Cryotherapy only	Procedure: Cryotherapy; 1-2 sprays, 5 seconds each, with a 5 second interval

Outcome Measures

Primary Outcome Measures :

1. Safety of Combination Therapy vs Cryotherapy Alone [ Time Frame: Day 57 ]
   To evaluate the safety of cryotherapy plus ingenol mebutate on dorsal hands and compare it to the safety of cryotherapy alone looking at Adverse Events.

Secondary Outcome Measures :

1. Change in Number of All Actinic Keratoses [ Time Frame: Baseline and Day 57 ]
   To evaluate and compare the mean reduction in number of all AKs (hypertrophic and non-hypertrophic) on the dorsal hands of the combination cryotherapy- ingenol mebutate treated side vs. the cryotherapy alone side on Day 57 as compared to baseline
2. Change in Actinic Keratoses by Anatomic Site [ Time Frame: Baseline and Day 57 ]
   To evaluate the number of AKs (both hypertrophic and non-hypertrophic) before therapy by anatomic site (dorsal hand) at Day 57 as compared to baseline

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adults at least 18 years old.
• Subjects must be in good general health as confirmed by the medical history.
• Subjects must be able to read, sign, and understand the informed consent
• Prior to cryosurgery, subjects have at least 3 hypertrophic actinic keratoses on each dorsal hand.
• Subject must be willing to forego any other treatments on the dorsum of the hands, including tanning bed use and excessive sun exposure while in the study.
• Subject is willing and able to participate in the study as an outpatient, making frequent visits to the study center during the treatment and follow-up periods 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:

• Subjects with a history of melanoma anywhere on the body.
• Subjects with an unstable medical condition as deemed by the clinical investigator.
• Subjects with non-melanoma skin cancer on the dorsum of the hands.
• 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.
• Subjects who have previously been treated with ingenol mebutate: on the dorsum of the hands in the past 6 months; or outside of the study area within the past 30 days.
• Women who are pregnant, lactating, or planning to become pregnant during the study period.
• Subjects who have experienced a clinically important medical event within 90 days of the visit (e.g., stroke, myocardial infarction, etc).
• Subjects who have active chemical dependency or alcoholism as assessed by the investigator.
• Subjects who have known allergies to any excipient in the study gel.
• 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 who have received any of the following within 90 days prior to study treatment initiation:

  • interferon or interferon inducers
  • cytotoxic drugs
  • immunomodulators or immunosuppressive therapies (inhaled/ intranasal steroids are permitted)
  • oral or parenteral corticosteroids
  • topical corticosteroids if greater than 2 gm/day
  • any dermatologic procedures or surgeries on the study area (including any AK treatments)
• Subjects who have used any topical prescription medications on the study area within 30 days prior to study treatment initiation.

Contacts and Locations

Locations

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 11370

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai

LEO Pharma

Investigators

• Principal Investigator: Gary Goldenberg, MD; Icahn School of Medicine at Mount Sinai

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hashim PW, Nia JK, Singer S, Goldenberg G. An Investigator-initiated Study to Assess the Safety and Efficacy of Ingenol Mebutate 0.05% Gel When Used After Cryosurgery in the Treatment of Hypertrophic Actinic Keratosis on Dorsal Hands. J Clin Aesthet Dermatol. 2016 Jul;9(7):16-22. Epub 2016 Jul 1.

• Responsible Party: Gary Goldenberg, Assistant Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT02251652
• Other Study ID Numbers: GCO 13-0142
• First Posted: September 29, 2014
• Results First Posted: April 26, 2017
• Last Update Posted: April 26, 2017
• Last Verified: March 2017

Keywords provided by Gary Goldenberg, Icahn School of Medicine at Mount Sinai:

Actinic

Additional relevant MeSH terms:

Keratosis, Actinic; Keratosis; Skin Diseases; Precancerous Conditions; Neoplasms