A Phase 1, Open-Label Clinical Trial to Assess the Safety, Tolerability, and Preliminary Efficacy Study of Topically Administered LUT017 Gel for Cutaneous Wound Healing
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
研究概览
简要总结
This research study is investigating a new topical medication called LUT017, which is being developed to help heal chronic skin wounds, particularly those known as venous leg ulcers (VLUs). VLUs are open sores that commonly occur on the lower legs due to poor blood flow in the veins. These wounds can be painful, slow to heal, and difficult to treat, especially in older adults and people with conditions like diabetes or obesity.
LUT017 is a gel that will be applied directly to the surface of these wounds. The goal of the study is to find out if the gel is safe and well tolerated when applied once a week for up to 8 weeks. The researchers will also look for early signs of whether the gel helps the wounds heal more quickly or completely. The gel contains a medicine that has been shown in animal studies to activate natural skin repair processes and promote cell growth, potentially speeding up the healing process.
The study will involve between 12 and 18 adult participants who have had a chronic leg wound for at least 4 weeks. All participants will go through a screening process to make sure they are eligible. If they qualify, they will first complete a two-week "run-in" phase where their wound will be treated with standard medical bandages. This phase helps ensure that only participants whose wounds are not healing with normal care are included.
If participants remain eligible after this period, they will start the treatment phase. During this phase, they will come to the clinic once a week for 8 weeks to receive the LUT017 gel treatment directly on their wound. Each visit will include a physical exam, vital signs, wound evaluation, photographs of the wound, and blood tests to monitor safety.
After the 8-week treatment period, participants will return for two follow-up visits-one at 3 months and one at 6 months after their first treatment. These visits will help the researchers understand how long any benefits of the treatment might last and monitor for any delayed side effects.
In total, participants will be involved in the study for about 6.5 months and will have approximately 12 to 14 visits to the clinic. Participation is entirely voluntary, and individuals can withdraw at any time. The research team is committed to ensuring participant safety and privacy throughout the study.
详细描述
Study Overview and Clinical Context
This is a Phase 1, open-label, dose-escalation clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary biological activity of LUT017 gel when administered topically to subjects with venous leg ulcers (VLUs) and other chronic non-healing cutaneous wounds. The study represents the first clinical investigation of LUT017 in the setting of impaired cutaneous wound healing and is intended to establish an initial safety profile, characterize systemic exposure following topical administration, and inform dose selection for future controlled studies.
Venous leg ulcers represent the most advanced clinical manifestation of chronic venous insufficiency and arise as a consequence of sustained venous hypertension, microvascular dysfunction, leukocyte trapping, and chronic inflammatory signaling within the lower extremities. The resulting wound environment is characterized by persistent cytokine activation, excessive matrix metalloproteinase activity, impaired fibroblast and keratinocyte responsiveness, oxidative stress, and altered extracellular matrix turnover. These processes lead to delayed epithelial migration, impaired re-epithelialization, and prolonged wound chronicity. Despite optimized compression therapy and local wound management, a substantial proportion of VLUs fail to heal within clinically acceptable timeframes. There are currently no approved pharmacologic agents specifically designed to activate regenerative signaling pathways in chronic wound beds.
The therapeutic hypothesis underlying this study is that localized activation of epidermal regenerative pathways may restore proliferative and migratory capacity in chronic wounds without inducing systemic toxicity. LUT017 has been developed to achieve this objective through paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type keratinocytes.
Mechanistic Rationale
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with venous leg ulcers (VLU), defined by open skin lesion of the leg as a result of venous hypertension.
- •Subject must be ≥ 18 years of age.
- •Active lower extremity ulceration (CEAP classification of C6).
- •Non-healing VLU ≥ 4 weeks but not greater than 24 months.
- •Ulcer size ≥ 2cm2 ≤ 20cm
- •a. Target ulcer will be defined as the largest ulcer on the affected limb. Only one wound per subject will be designated as the study wound and treated with the investigational gel. If a subject has two wounds separated by less than 1 cm of intact skin, these wounds will be considered a single study wound, and the surface areas of both wounds will be added together for eligibility purposes; if the combined area exceeds 20 cm², the subject will be excluded from the study. Although only one wound will be directly treated, local activation of the MAPK pathway may result in biological stimulation of the adjacent untreated wound when wounds are separated by less than 1 cm.
- •Chronic venous insufficiency confirmed by ultrasound within previous 12 months.
- •Adequate perfusion confirmed within the past 12 months.:
- •Dorsalis Pedis (DP) or Posterior Tibial (PT) systolic pressure ≥ 60mmHg on the study limb.
- •Transcutaneous partial pressure oxygen (TcP02) > 30mmHg.
- •Great toe systolic pressure > 40mmHg.
- •Must be able and willing to provide informed consent prior to study participation.
- •Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at baseline (Day 0). They should agree to use highly effective methods of birth control, defined as those with failure less than 1%, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUD's), sexual abstinence, or a vasectomized partner. Such subjects should agree to have monthly pregnancy test documented.
排除标准
- •Target ulcer has exposed of tendon, muscle, or bone.
- •Target ulcer is of non-venous etiology.
- •Target ulcer has been treated with living cellular therapy within 4 weeks of the randomization.
- •Target ulcer shows any signs of infection (only non-infected ulcers are eligible).
- •Patient has undergone endovenous ablation or other venous surgery within 4 weeks of enrollment.
- •Unable to tolerate multi-layer bandages or compression garments.
- •Decompensated congestive heart failure within 4 weeks of screening.
- •Active soft tissue or bone infection requiring antibiotics.
- •Skin cancer on the target limb within the last 24 months.
- •Actively receiving chemotherapy and/or radiation therapy for cancer.
- •Treatment with a serine/threonine-protein kinase BRAF inhibitor, including but not limited to Zelboraf® (vemurafenib), Tafinlar® (dabrafenib), BraftoviTM (encorafenib) or Nexavar® (sorafenib), within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer.
- •Blood chemistry or counts values as follows:
- •White Blood Cells (WBC)< 1.5 x 109/L.
- •Absolute < 0.9 x 109/L.
- •Platelet count < 50 x 109/L.
- •Alanine aminotransferase > 3 x upper limit of normal.
- •Aspartate aminotransferase > 3 x upper limit of normal.
- •Serum albumin <2.0 g/dL.
- •HbA1c value of > 12% within the past three (3) months.
- •Current use of systemic corticosteroids > 5 mg daily or equivalent within 4 weeks.
- •Currently pregnant or trying to become pregnant.
- •Inability or unwillingness to participate in all aspects of study protocol or as determined by the Investigator.
- •Known hypersensitivity to the ingredients of the study drug.
研究组 & 干预措施
LUT017 Gel 0.03% Once Weekly
Participants receive LUT017 gel 0.03% (0.3 mg/g) applied topically once weekly for up to 8 weeks to a designated chronic venous leg ulcer or non-healing cutaneous wound. Treatment is administered in clinic following a 14-day run-in period of standardized wound care. Safety, tolerability, pharmacokinetics, and wound healing parameters are evaluated throughout treatment and follow-up.
干预措施: LUT017 gel (Drug)
LUT017 Gel 0.1% Once Weekly
Participants receive LUT017 gel 0.1% (1.0 mg/g) applied topically once weekly for up to 8 weeks to a designated chronic venous leg ulcer or non-healing cutaneous wound. Treatment is administered in clinic following a 14-day run-in period of standardized wound care. Dose escalation proceeds according to a 3+3 design based on observed safety.
干预措施: LUT017 gel (Drug)
LUT017 Gel 0.25% Once Weekly
Participants receive LUT017 gel 0.25% (2.5 mg/g) applied topically once weekly for up to 8 weeks to a designated chronic venous leg ulcer or non-healing cutaneous wound. Enrollment in this cohort occurs after safety review of lower dose levels under the predefined dose-escalation rules.
干预措施: LUT017 gel (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
时间窗: From first dose (Day 0) through Week 8 (end of treatment period)
Number and percentage of participants experiencing treatment-emergent adverse events (AEs), including adverse drug reactions (ADRs), serious adverse events (SAEs), unexpected adverse events, AEs leading to discontinuation, and AEs leading to death. Adverse events are graded according to CTCAE criteria and assessed for relationship to study drug.
次要结局
- Change in Wound Area Over Time(Baseline through Week 8, Month 3, and Month 6)
- Rate of Complete Re-epithelialization(Week 8, Month 3, and Month 6)
- Time to Complete Re-epithelialization(From Day 0 through Month 6)
研究者
Antoni Ribas
Professor of medicine, surgery, and molecular and medical pharmacology at UCLA
University of California, Los Angeles