A Prospective, Randomized, Single-Blind Phase 2a Multi-Center Dose Comparative Study to Evaluated The Safety, Tolerability, and Antimicrobial Efficacy Of Topically Twice Daily Applied Bisphosphocin Nu-3 Gel At a 2%, 5%, And 10% Concentration To Infected Diabetic Foot Ulcers (iDFU)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 6
- 主要终点
- Primary Efficacy Outcome
研究概览
简要总结
The goal of this clinical trial is to learn if drug Nu-3 works to treat mildly infected diabetic foot ulcers in adults with Type 1 or Type 2 diabetes at 3 different dose levels. It will also learn about the safety of drug Nu-3. The main questions it aims to answer are:
Does drug Nu-3 lower the number of bacteria or viruses in the infected ulcer, or cure patients of the infection, at any or all of the dose levels being tested after 1 week or 2 weeks? What medical problems do participants have when taking the topical drug Nu-3? Researchers will compare drug Nu-3 at different dose levels to see if drug Nu-3 works to treat the infected ulcers at each of the dose levels.
Participants will:
Take drug ABC or a placebo every day for 4 months Visit the clinic once every 2 weeks for checkups and tests Keep a diary of their symptoms and the number of times they use a rescue inhaler
详细描述
A prospective, randomized, single-blind Phase 2a multi-center dose comparative study to evaluate the safety, tolerability, and antimicrobial efficacy of topically twice daily applied Bisphosphocin® Nu-3 gel at a 2%, 5%, and 10% concentration to infected diabetic foot ulcers (iDFU) in adult subjects with type 1 and 2 diabetes. The study will be conducted in 3 phases: Screening, Treatment, and Follow-up.
Subjects will have the study explained to them and will be provided with the study specific informed consent form (ICF). For eligible subjects, the screening evaluations will be performed immediately after the subject provides a written informed consent. To further increase the probability of patients being enrolled who truly have a mildly infected diabetic foot ulcer (and not either no infection or a moderate or more severe infection) an additional external clinical specialist(s) will be consulted and provided with pictures obtained during the screening procedure. If the external specialist(s) confirms eligibility, the patient can be included. If the clinical specialist(s) has additional questions to determine the eligibility or disagrees with the study PI's assessment, a resolution call between the PI and the external specialist(s) takes place the same day. The specialist(s) may also join via appropriate telehealth technology to discuss other signs and symptoms which are difficult to be assessed via images with the site PI and the patient together. Only if consensus has been reached that the patient is eligible for the trial by wound status and all other inclusion and no exclusion criteria have been met, the baseline visit will be scheduled for the next morning. If consensus cannot be reached the patient will not be enrolled and recorded as screen failure as defined in the Safety Charter provided by CRO.
Enrollment and randomization need to take place as soon as screening lab-results from a local laboratory and possibly a plain foot X-ray have been obtained, because infection management will not permit a delay in enrollment and start of treatment for several days. If the patient does not meet eligibility criteria, the patient will not be randomized and will be considered a screening failure for the study. Subjects enrolled in the study at V2 will be followed by five scheduled visits plus an additional follow-up visit on day 28 (total = 7 visits from baseline until end of study).
Eligible subjects who enter the active treatment period will be randomized into one of the dose cohorts:
- Treatment/ Cohort 1: 2% Nu-3 gel + SOC (n = 8-10) twice daily
- Treatment/ Cohort 2: 5% Nu-3 gel + SOC (n = 8-10) twice daily
- Treatment/ Cohort 3:10% Nu-3 gel + SOC (n = 8-10) twice daily Study drug will be applied to the target iDFU for 14 days (± 2 days) twice daily.
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
- Double (Participant, Outcomes Assessor)
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
- •Male and female subjects ≥18 years of age.
- •Voluntary written informed consent, including information about the provisions of the Health Insurance Portability and accountability act (HIPAA) as applicable.
- •Non-hospitalized ambulatory subjects diagnosed with diabetes mellitus, Type I or II per ADA criteria with signs of a localized mild foot infection as defined by the IDSA infection severity criteria (Lipsky,2012). The presence of purulent drainage or at least two of the following criteria:
- •i. erythema, ii. warmth, iii. pain or tenderness, iv. edema, or v. induration (The diagnosis of mild infection must be confirmed immediately following debridement at Baseline).
- •The target ulcer is classified as a grade 1 ulcer according to the Wagner Scale (Wagner 1979). The ulcer is a superficial, full-thickness ulcer limited to the dermis, not extending to the subcutis. Target ulcer is >1 cm2 and <12 cm2 post debridement at baseline and must be no higher than the ankle, on or below the malleolus (ankle bone) with ≥50% below the malleolus.
- •Adequate vascular perfusion as evidenced by one of the following:
- •Dorsal transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 40 mmHg
- •Ankle Branchial Index (ABI) between 0.9 and 1.3 within 3 months of Screening using the extremity with the target ulcer.
- •Arterial Doppler ultrasound evaluating for biphasic or triphasic dorsalis pedis and posterior tibial vessels at the level of the ankle or a TBI (Toe Brachial Index) of >0.
- •Subject has a caregiver who will attend the Baseline visit (V2) and/or watch the dosing and dressing demonstration video and apply wound treatment along with study dressings for the study duration.
- •Must meet one of the following criteria:
- •a. Female subjects of Non-Child-Bearing Potential i. Postmenopausal for at least 1 year ii. Surgically sterilized (i.e., hysterectomy or bilateral oophorectomy more than 3 months prior to Screening) iii. Bilateral tube ligation > 6 months prior to screening iv. A negative serum β-hCG pregnancy test at screening and no breastfeeding after the administration of the study drug.
- •b. Male subjects of Non-Childbearing Potential defined as: i. Vasectomized subjects for > 6 months prior to Screening ii. Those diagnosed as sterile by a physician. c. Females and Males of Childbearing Potential who practice an acceptable method of contraception defined as the i. Use of any form of hormonal contraceptive ii. Use of a barrier method with spermicide, condoms, intrauterine device, iii. Abstinence from sexual intercourse starting at least 60 days prior to Screening and continuing at least 14 days following the last treatment.
- •Subjects must be willing to undergo all clinical investigation-related procedures, attend all required visits, and cooperate fully with the investigator and site personnel.
- •Subject must be willing to wear offloading RCW, if necessary (defined as ulcer at plantar site of the foot, see Appendix 6), throughout the duration of the clinical treatment.
- •Subject must have plain radiograph taken at screening and prior to randomization showing no evidence of bony abnormalities consistent with osteomyelitis, or gas compatible with tissue crepitus, in the affected foot.
排除标准
- •Ulceration with exposed tendon, capsule, or bone
- •IDSA-defined moderate or severe DFU infection.
- •Infected diabetic foot ulcer that is associated with local wound complications such as prosthetic materials or protruding surgical hardware.
- •> 1 infected foot ulcer
- •Subject is currently receiving topical antimicrobial treatment for a localized infection of the study ulcer or received such topical antimicrobial treatment < 72 hours prior to study enrollment.
- •Subject has received systemic treatment with a long-lasting antibiotic such as azathioprine (within less than 10 days prior to Screening) or any other systemic antibiotic within 48 hours prior to Screening.
- •Concurrent or expected to require systemic antimicrobials during the active treatment study period for any infection including diabetic foot ulcer.
- •Any subject that has active viral hepatitis (A, B, C) and/or untreated HIV/AIDS.
- •Any subject that has vascular compromise requiring surgical intervention or has undergone vascular reconstruction or angioplasty less than 1 month prior to randomization. Any planned surgical procedures during the study participation
- •eGFR <60 and/or subject on hemodialysis within 3 months prior to randomization.
- •Hemoglobin A1c (HbA1c) >12% within 3 months prior to randomization.
- •Aspartate Aminotransferase (AST, GOT) and/or Alanine Aminotransferase (ALT, GPT) >3.0 x the upper limit of normal and/or bilirubin >1.5 x the upper limit of normal within 3 months prior to randomization.
- •Acute active Charcot foot
- •Any subject that would be unable to safely monitor the infection status at home and return for scheduled visits.
- •History of immunosuppression within 3 months prior to randomization, or taking immunosuppressive agents including systemic corticosteroids, except stable daily doses of 5 mg/day or less for chronic conditions
- •Any subject with a life expectancy ≤ 6 months
- •Use of investigational drugs within 28 days prior to screening
- •Use of Aspirin® or acetylsalicylic acid containing medication (except low-dose aspirin) < 7 days before baseline,
- •Use of oral anticoagulants (e.g., warfarin, Xarelto® or comparable products).
- •History of concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol including known or suspected active abuse of alcohol, narcotics, or non-prescription drugs.
- •Prior randomization in this clinical trial, or a previous Bisphosphocin study
研究组 & 干预措施
10mg dose
Twice daily application for 14 days
干预措施: Antimicrobial agent (Drug)
5mg dose
Twice daily application for 14 days
干预措施: Antimicrobial agent (Drug)
2.5mg dose
Twice daily application for 14 days
干预措施: Antimicrobial agent (Drug)
结局指标
主要结局
Primary Efficacy Outcome
时间窗: From enrollment to the end of day 7 and at the end of treatment at day 14
The rate reduction in CFUs by ≥ 2 logs per pathogen, which is identified as typical and highly suspicious for being the cause of the infection compared to baseline.
Primary Safety Outcome
时间窗: From enrollment to the end of study participation at 4 weeks
Number of AEs overall and those assessed by the investigators as possibly, probably, and definitely related to the study drug as well as the number of SAEs per patient and cohort.
次要结局
- Treatment success by dose(From enrollment to the end of treatment at 2 weeks)
- Treatment failures by dose(From enrollment to the end of treatment at 2 weeks)
- Secondary safety outcomes(From enrollment to 7 days of treatment, end of treatment at 2 weeks, and end of study participation in the study at 4 weeks)