A clinical trial with blinded patients and personnel investigating the safety and preliminary dose-finding effects of the medicinal product LL-37 in hard-to-heal leg ulcers in comparison with an inactive substance (placebo)
- Conditions
- Hard-to-heal (HTH) venous leg ulcerMedDRA version: 14.1Level: LLTClassification code 10066677Term: Chronic leg ulcerSystem Organ Class: 100000004858Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2012-002100-41-SE
- Lead Sponsor
- ipopeptide AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 35
1.Male subjects >18 years of age and post-menopausal or clinically sterile women.
2.Subjects with VLU, or combined venous-arterial ulcers with predominant venous component.
3.Subjects whose leg ulcers have failed to heal within 6 weeks of compression therapy.
4.Ankle-Brachial Pressure Index (ABI) >0.70 at screening.
5.Ulcer localization above the foot and below the knee (wrist and malleoli included).
6.Surface area of target ulcer 1-40 cm2 at screening.
7.Ulcer essentially free of necrotic tissue.
8.Ability to tolerate compression bandaging.
9.Subjects should be in an appropriate state of health to participate in the study, as determined by the Investigator. This will be determined by a medical history, physical examination, and clinical laboratory evaluations.
10.Subjects willing to attend study site visits and able to communicate effectively.
11.Subjects who have voluntarily signed and dated a patient IRB/EC approved Informed Consent Form (ICF).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35
1.Other known predominant etiology than VLU of the target ulcer.
2.Malignant disease (excluding basal cell carcinoma) unless in remission for 5 years.
3.Subjects who have a past or present disease that, which as judged by the Investigator, may affect the safety of the subject or the outcome of the study.
4.Hematology values deviating 25% or more from the upper or lower limits of the normal range, and judged by the Investigator to affect the safety of the subject or the study outcome.
5.Liver function tests (ALT, AST, ALK PHOS and bilirubin) deviating 50% or more from the upper normal limits, and judged by the Investigator to affect the safety of the subject or the study outcome..
6.P-albumin <25 g/L or HbA1C >10%.
7.Presence of active psoriasis skin lesions within 1.5 cm of the ulcer area.
8.Ulcer that by location or extension will either be difficult to assess or to treat according to the protocol.
9.Presence of a non-study ulcer within 1 cm of the target VLU.
10.Exposure of bone, tendon or fascia within the target wound.
11.Clinical signs or symptoms of a clinical wound infection, erysipelas, or osteomyelitis.
12.Systemic immunosuppressive drugs with the exception of low-dose oral steroids: glucocorticoids corresponding to oral Prednisolone =10 mg/day, which is allowed provided that drug treatment was initiated within 4 weeks prior to screening visit, and at that time point, expected to be maintained at similar dose level throughout the study period. Also, mineral corticoids may be permitted.
13.Known hypersensitivity to any component of the trial product or standard wound dressing allowed during study treatment period or follow-up period.
14.Systemic treatment with antibiotics for target ulcer infection within 7 days prior to screening visit.
15.Participation in another clinical trial within 7 days prior to screening visit
16.Treatment with any of the following medications: topical antibiotics, and potassium permanganate.
17.Reduction in wound area per week* during run-in period:
a. >7% for a an ulcer with an initial area of >10 cm2
b.>10% for an ulcer with an initial area of 2-10 cm2
c.>13% for an ulcer with an initial area of <2 cm2
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objectives of the study are to determine the safety and tolerability of LL 37.;Secondary Objective: The secondary objective is to achieve preliminary dose response data in wound healing as a prerequisite for planning a larger Phase II dose-ranging study. ;Primary end point(s): The study is primarily designed to assess the safety of LL-37 based on the following primary endpoints:<br>• Incidence of severe local reactions in wound and adjacent skin as exemplified by clinical signs of inflammation (edema, redness, odor and raised temperature) or skin irritation (scaling, redness, papules, vesicles, pustules). Any local reaction will be recorded on a graded scale (0-3). <br>• Incidence of >30% increase in wound area of relative to baseline<br>• Change in laboratory values and vital signs from baseline<br>• Overall incidence of AEs<br>;Timepoint(s) of evaluation of this end point: End of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The secondary endpoints are chosen to assess the efficacy of LL-37. Data will be collected to address the following endpoints:<br>• Wound healing rate within the study period.<br>• Number of ulcers attaining >30% area reduction from baseline.<br>• Changes in local pain using the VAS score (0-10). <br>• Change in wound characteristics (scores of slough, exudation, granulation tissue, necrosis) from baseline (scale 0-3).<br>;Timepoint(s) of evaluation of this end point: End of treatment