Safety and Efficacy of Ingenol Mebutate Once Daily for 2 or 3 Consecutive Days in Subjects With Actinic Keratosis

NCT01820260 | Completed Phase 1 Results

• 1 other identifier: LP0105-1012
• Study Type: interventional
• Target: 395
• Locations: 1 country
• Sites: 1

Brief Summary

To identify the Maximum Tolerated Dose levels of ingenol mebutate gel after once daily treatment for 2 or 3 consecutive days and to evaluate efficacy of ingenol mebutate gel in different doses after once daily treatment for 2 or 3 consecutive days compared to vehicle gel

Conditions

Actinic Keratosis

Outcome Measures

Primary Outcomes (2)

• Part 1: To Identify the Maximum Tolerated Dose (MTD) Levels After Once Daily Treatment for 2 or 3 Days

  Dose tolerability was measures looking at the composite score of Local Skin Responses (LSR). The MTD was defined as the highest dose level with less than 4 subjects out of 12 experiencing dose limiting toxicity (DLT). DLT was defined as one or more of the following three local skin LSRs: * Crusting Grade 4 * Erosion/Ulceration Grade 4 * Vesiculation/Pustulation Grade 4 or two or more of the following five LSRs: * Erythema Grade 4 * Crusting Grade 3 * Swelling Grade 4 * Erosion/Ulceration Grade 3 * Vesiculation/Pustulation Grade 3 The grading is a scale of 1 to 4 (highest grade).

  8 days after initial treatment

• Part 2: Number of Subjects With Complete Clearance of AKs

  Number of subjects with complete clearance of Actinic Keratosis lesions (AKs) at week 8 after 2 or 3 consecutive days of treatment with ingenol mebutate gel on the full face, full balding scalp or approximately 250 cm² on the chest

  8 weeks

Secondary Outcomes (2)

• Part 2: Reduction in AK Count

  From baseline to Week 8

• Part 2: Number of Subjects With Partial Clearance of AKs

  Week 8

Study Arms (14)

Part 1A: Ingenol mebutate gel 0.005%

EXPERIMENTAL

Open-label, dose escalation, 3 days treatment

Drug: Ingenol mebutate gel

Part 2: Ingenol mebutate gel 0.018% for 3 days treatment

ACTIVE COMPARATOR

Randomized, 3 days treatment

Drug: Ingenol mebutate gel

Part 2: Ingenol mebutate gel 0.018% for 2 days treatment

ACTIVE COMPARATOR

Randomized 2 days treatment

Drug: Ingenol mebutate gel

Part 2: Ingenol mebutate gel 0.027% for 3 days treatment

ACTIVE COMPARATOR

Randomized 3 days treatment

Drug: Ingenol mebutate gel

Part 2: Ingenol mebutate gel 0.027% for 2 days treatment

ACTIVE COMPARATOR

Randomized 2 days treatment

Drug: Ingenol mebutate gel

Part 2: Placebo for 3 days treatment

PLACEBO COMPARATOR

Randomized 3 days treatment

Drug: placebo

Part 2: Placebo for 2 days treatment

PLACEBO COMPARATOR

Randomized 2 days treatment

Drug: placebo

Part 1A: Ingenol mebutate gel 0.008%

EXPERIMENTAL

Open-label, dose escalation, 3 days treatment

Drug: Ingenol mebutate gel

Part 1A: Ingenol mebutate gel 0.012%

EXPERIMENTAL

Open-label, dose escalation, 3 days treatment

Drug: Ingenol mebutate gel

Part 1A: Ingenol mebutate gel 0.027%

EXPERIMENTAL

Open-label, dose escalation, 3 days treatment

Drug: Ingenol mebutate gel

Part 1A: Ingenol mebutate gel 0.04%

EXPERIMENTAL

Open-label, dose escalation, 3 days treatment

Drug: Ingenol mebutate gel

Part 1B: Ingenol mebutate gel 0.06%

EXPERIMENTAL

Open-label, dose escalation, 2 days treatment

Drug: Ingenol mebutate gel

Part 1A: Ingenol mebutate gel 0.018%

EXPERIMENTAL

Open-label, dose escalation, 3 days treatment

Drug: Ingenol mebutate gel

Part 1B: Ingenol mebutate gel 0.04%

EXPERIMENTAL

Open-label, dose escalation, 2 days treatment

Drug: Ingenol mebutate gel

Interventions

Ingenol mebutate gel DRUG

Part 1A: Ingenol mebutate gel 0.005%; Part 1A: Ingenol mebutate gel 0.008%; Part 1A: Ingenol mebutate gel 0.012%; Part 1A: Ingenol mebutate gel 0.018%; Part 1A: Ingenol mebutate gel 0.027%; Part 1A: Ingenol mebutate gel 0.04%; Part 1B: Ingenol mebutate gel 0.04%; Part 1B: Ingenol mebutate gel 0.06%; Part 2: Ingenol mebutate gel 0.018% for 2 days treatment; Part 2: Ingenol mebutate gel 0.018% for 3 days treatment; Part 2: Ingenol mebutate gel 0.027% for 2 days treatment; Part 2: Ingenol mebutate gel 0.027% for 3 days treatment

placebo DRUG

Part 2: Placebo for 2 days treatment; Part 2: Placebo for 3 days treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be competent to understand the nature of the trial and provide informed consent
• Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on either the face, the balding scalp (the balding part of the scalp should be at least 25 cm2) or a contiguous area of approximately 250 cm2 on the chest
• Subject at least 18 years of age
• Female subjects must be of either:
• Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus) or,
• Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment, to rule out pregnancy
• Female subjects of childbearing potential1 must be willing to use effective contraception at trial entry and until completion

You may not qualify if:

• Location of the treatment area (full face, full balding scalp or chest)
• within 5 cm of an incompletely healed wound,
• within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC
• Prior treatment with ingenol mebutate gel within the treatment area
• Lesions in the treatment areas that have:
• atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or,
• recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions
• History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum)
• Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment areas.
• Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety and efficacy during the course of the trial, as determined by the investigator's clinical judgment
• Any abnormal laboratory tests that are medically significant and would impact the safety of the subjects or the interpretation of the trial results, as determined by the investigator's judgment
• Anticipated need for hospitalisation or out-patient surgery during the first 15 days after the first trial medication application. Note that cosmetic/therapeutic procedures are not excluded if they fall outside of the criteria detailed in Prohibited Therapies or Medications
• Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel
• Presence of acute sunburn within the treatment areas
• Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial.

Sponsors & Collaborators

• LEO Pharma: lead

Study Sites (1)

Laser & Skin Surgery Center of Inidana

Carmel, Indiana, 46032, United States

Location

MeSH Terms

Conditions

Keratosis, Actinic

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Clinical Trial Disclosure Manager
• Organization: LEO Pharma A/S

ctr.disclosure@leo-pharma.com

+45 4494 5888

Study Officials

• C. William Hanke, MD

  Laser & Skin Surgery Center of Indiana

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking only for Part 2
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 was an open-label, dose escalation. Part 2 was a randomised, double-blind, parallel group

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: March 28, 2013
• Study Start: April 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: March 13, 2025
• Results First Posted: May 25, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)