A Randomized, Double-Blind, Placebo-controlled, Parallel, Exploratory Phase 2a Study to Evaluate Safety and Biological Effect on Wound Healing of ILP100-Topical in Subjects With Diabetic Foot Ulcers
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Compare incidence of serious adverse events (SAEs) between treatment groups
研究概览
简要总结
A randomized, double-blind, placebo-controlled, parallel, exploratory phase 2a study to evaluate safety and biologic efficacy on wound healing of ILP100-Topical in subjects with diabetic foot ulcers during 26 weeks with a 5-year long-term follow-up period. A total of 30 subjects will be randomized to low dose of ILP100-Topical (ILP100Lo), high dose of ILP100-Topical (ILP100Hi) or Placebo according to a 1:1:1 randomization schedule.
The study will consist of a 3-weeks Screening and Run-in Phase, followed by a 5-week Treatment Phase starting from Baseline and an Assessment Phase from Week 5 to Week 26. Thereafter, the subjects will be followed yearly during 5 years in a Long-Term Safety Follow-up Phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study, and the allocation of treatments will not be disclosed to subjects, Investigator or Independent Evaluators until database lock after all subjects (who were not withdrawn) completed Week 26.
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
- •Signed written informed consent
- •Males and females aged ≥18 years
- •Diagnosis of diabetes mellitus type 1 or 2
- •HbA1c ≤ 86 mmol/mol (≤ 10%) at Screening
- •Subjects with at least one first time or recurrent full thickness ulcer (at or below the ankle) which fulfils all of the following criteria at Screening and at the time of Baseline:
- •A non-interdigital wound
- •Accessible for administration of IMP, wound study assessments and procedures
- •Persistence of the wound for at least 6 weeks at Baseline
- •Assessed by the investigator to be of non-venous etiology.
- •Minimum full skin ulcer without undermining, with no exposed muscle, tendon or bone
- •A wound area of 1.0 - 5.0 cm^2 after sharp or mechanical debridement at Screening
- •During the 2-weeks between start of Run-in Phase and Baseline the wound size must not decrease by more than 30% or increase by more than 25%, which correspond to wound areas of 0.7 - 6.3 cm^2, or at Screening expected by the Investigator to have a high probability for wound size changes within this range during this period.
- •Toe pressure ≥20 mm Hg
- •Expected to comply with the study procedures
排除标准
- •Infected index wound with clinical signs of inflammation at Screening or Baseline.
- •The index wound determined as heavily exuding defined as requiring more than 1 dressing change per day or requiring use of super absorbent dressing
- •Wound duration longer than 2 years
- •Active Charcot deformity of the study foot
- •Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2
- •Hemoglobin concentration <100 g/L at Baseline
- •Planned or ongoing treatment with corticosteroids to an equivalent dose of prednisolone >10 mg per day or other immunosuppressive therapy, or such treatment within 4 weeks prior to Baseline
- •Has any major surgery or hospitalization planned up to Week 26
- •Has changed a treatment for diabetes during the last 3 weeks before Baseline. Dose change is allowed
- •Ongoing treatment with dipeptidyl peptidase 4 (DPP-4) inhibitors
- •Revascularization procedure in the index wound leg planned or undertaken within 8 weeks before Screening, or under investigation
- •Current smokers
- •Participation in other clinical studies or having received any investigational treatment within 1 month or at the earliest five times the half-life prior to Screening
- •Has any disease conditions, including ulcerative dermatological disorders and vasculitis, or comorbidities which is expected to prevent the subject from participating in the study or confounding the evaluation of the safety profile and effect on wound healing of ILP100
- •Pregnant or lactating woman
- •Male subjects not willing to use a condom and refrain from donating sperm
- •Female subjects of childbearing potential unless they use a contraceptive method with a failure rate of < 1% to prevent pregnancy
研究组 & 干预措施
ILP100Lo
During the Treatment Phase, subjects will continue on standard of care according to the protocol and ILP100Lo (ILP100-Topical, 5x10^7 colony forming units (CFU)/cm^2) will be topically administered at two occasions on Day 1 (Baseline and Hour 2), Days 2, 3, and thereafter every second to third day until Day 31.
干预措施: ILP100-Topical (emilimogene sigulactibac) 5x10^7 CFU/cm^2 (Biological)
ILP100Hi
During the Treatment Phase, subjects will continue on standard of care according to the protocol and ILP100Hi (ILP100-Topical, 1x10^9 CFU/cm^2) will be topically administered at two occasions on Day 1 (Baseline and Hour 2), Days 2, 3, and thereafter every second to third day until Day 31.
干预措施: ILP100-Topical (emilimogene sigulactibac) 1x10^9 CFU/cm^2 (Biological)
Placebo
During the Treatment Phase, subjects will continue on standard of care according to the protocol and Placebo (ILP100 dilution buffer mixed with the activation peptide SppIP) will be topically administered at two occasions on Day 1 (Baseline and Hour 2), Days 2, 3, and thereafter every second to third day until Day 31.
干预措施: Placebo (Biological)
结局指标
主要结局
Compare incidence of serious adverse events (SAEs) between treatment groups
时间窗: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
The incidence of SAEs up to Week 26 will be presented for each treatment group and by category, causality, severity and frequency.
Compare incidence of adverse events (AEs) between treatment groups
时间窗: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
The incidence of AEs up to Week 26 will be presented for each treatment group and by category, causality, severity and frequency.
次要结局
- Local tolerability by Investigator's assessment(Compare Investigator's local tolerability assessments up to Week 26 between the ILP100-Topical and Placebo treatment arms.)
- Proportion of subjects with a local tolerability parameter Grade ≥ 2 per Independent Assessor's Assessment(Compare the ILP100-Topical and Placebo treatment arms up to Week 26.)
- Proportion of subjects with recurrence of index wound(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- CXCL12 levels in plasma(Compare up to Week 16 between the ILP100-Topical and Placebo treatment arms.)
- Wound area reduction (percent of Baseline)(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- Proportion of subjects with ≥50% and 75% partially healed wounds(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- Time to partial (≥50% and 75%) and complete healing(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- Wound area(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- Proportion of subjects with new wound infections(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- Days on antibiotic treatment(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- Change in subject-reported wound-related pain(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- Long-term incidence of AEs.(Compare the ILP100-Topical and Placebo treatment arms up to Year 5 after initiation of treatment.)
- Wound healing rate(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- Proportion of subjects with completely healed wounds(Compare ILP100-Topical and Placebo treatment arms up to Week 26)
- Local tolerability by Independent Assessor's assessment(Compare local tolerability up to Week 26 between the ILP100-Topical and Placebo treatment arms.)
- Proportion of subjects with a local tolerability parameter Grade ≥ 2 per Investigator's Assessment(Compare the ILP100-Topical and Placebo treatment arms up to Week 26.)
- Presence of viable L. reuteri containing the pSIP_CXCL12 plasmid in wounds(Compare up to Year 5 between the ILP100-Topical and Placebo treatment arms.)