A Phase 2a Efficacy, Safety, Tolerability, and PK Study of Encochleated Amphotericin B (CAMB/MAT2203) in Patients With Mucocutaneous Candidiasis Who Are Refractory or Intolerant to Standard Non-Intravenous Therapies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Clinical Response to Treatment of Mucocutaneous Candidiasis
研究概览
简要总结
This is an open-label, dose-titration trial to study the efficacy, safety, and pharmacokinetics of oral cochleate amphotericin B (CAMB) in the treatment of mucocutaneous candidiasis infections in patients who are refractory or intolerant to standard non intravenous therapies.
详细描述
Patients aged 18 to 75 years with mucocutaneous candidiasis (esophageal, oropharyngeal, or vulvovaginal) who are refractory or intolerant to standard non-intravenous therapies will be enrolled. Patients will initially be treated in a short-term dose titration period, where the dose may be increased in patients that do not respond clinically. Patients who do not respond clinically to the highest dose of drug will discontinue the protocol. Patients that respond to treatment and tolerate the study medication will be eligible to enter a long-term extension (up to 60-months).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a clinical diagnosis of at least one of the following:
- •Persistent oropharyngeal candidiasis (OPC) for greater than or equal to 5 days documented on at least one occasion by potassium hydroxide (KOH) test or fungal stain and confirmed by mycological culture to be azole resistant within the previous 6 months and/or intolerance to standard non intravenous therapies or lack of improvement or worsening of OPC after receipt of appropriately dosed oral azole therapy.
- •Esophageal candidiasis (EC) associated with clinical symptoms of retrosternal pain, odynophagia, and/or pain with swallowing and documented by esophageal biopsy or visualization with culture documenting azole resistance within the previous 6 months and/or intolerance to standard non-intravenous therapies or lack of improvement or worsening of EC after appropriately dosed azole therapy.
- •Persistent vulvovaginal candidiasis (VVC) for greater than or equal to 5 days as documented by presence of vaginal symptoms and a positive wet mount showing Candida structures and confirmed by a vaginal culture positive for Candida with azole resistance within the previous 6 months and/or intolerance to standard non intravenous therapies or lack of improvement or worsening of VVC after appropriately dosed azole therapy.
- •Patient is expected to survive for greater than or equal to 6 months.
- •Willing to have samples stored for future research.
- •Agree to use highly effective contraception.
- •Contraception: Because the effects of CAMB on the developing human fetus are unknown, sexually active patients of childbearing potential must agree to use highly effective contraception as outlined below before study entry and for the duration of study participation. Females of childbearing potential must have a negative pregnancy test result before receiving CAMB. During the course of the study, if a patient becomes pregnant or suspects they are pregnant, then they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are:
- •Intrauterine device (IUD) or equivalent.
- •Hormonal contraceptives (eg, consistent, timely and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy prior to dosing). If the patient uses contraceptive pill, patch, or ring, then a barrier method (eg, male/female condom, cap, or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity.
- •Be in a stable, long-term monogamous relationship, per principal investigator (PI) assessment, with a partner that does not pose any potential pregnancy risk, eg, has undergone a vasectomy at least 6 months prior to first dose of study agent or is of the same sex as the patient.
- •Have had a hysterectomy and/or a bilateral tubal ligation or both ovaries removed.
排除标准
- •Allergy to any amphotericin B (AMB) product or any component of CAMB (eg, phosphatidylserine)
- •Have evidence of systemic fungal infections requiring intravenous antifungal therapy
- •Pregnant or nursing women, and women intending to become pregnant during the study period
- •Had a concomitant medical condition that could interfere with study drug evaluation or that is a contraindication to the proposed investigational treatment based upon known agent safety profile or toxicities.
- •Had any of the following laboratory abnormalities at the screening visit:
- •Alanine Transaminase (ALT), Aspartate Transaminase (AST) and Alkaline phosphatase (ALP) > 2.5 times the upper limit of normal (ULN).
- •Total bilirubin level > 2.5 times the ULN
- •Serum creatinine level > 2 times the ULN
- •Absolute neutrophil count less than 500 cells/microliter
- •Potassium level less than 3.5 mmol/L
- •Exposure to any investigational agent within 4 weeks prior to Day 0 (Baseline).
- •Current or recent history (past 12 months) of drug or alcohol abuse.
- •Use of intravenous AMB products within 1-week of start of study drug administration
- •Use of non-intravenous AMB products (such as oral AMB swishes) within 72 hours prior to start of study drug administration
- •Any other condition the investigator believes would interfere with the patient s ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the subject at undue risk.
研究组 & 干预措施
CAMB (Encochleated Amphotericin B)
Encochleated Amphotericin B (200 mg, 400 mg, 800 mg)
干预措施: Amphotericin B (Drug)
结局指标
主要结局
Clinical Response to Treatment of Mucocutaneous Candidiasis
时间窗: 14-days at highest titrated dose
Number of subjects with a clinical response of clinical cure or improvement. Clinical cure was defined as absence of signs or symptoms of infection. Clinical improvement was defined as follows: * OPC or EC: partial resolution defined as greater than or equal to 50% of Baseline signs or symptoms * VVC: reduction of greater than or equal to 50% of clinical severity score from Baseline Severity of each symptom was graded on a scale from zero (absence of symptoms) to 3 (severe symptoms). The sum of all scores for all symptoms was used as the clinical severity score. Higher scores mean worse outcomes.
次要结局
- Maximum Plasma Concentration (Cmax)(Single and Multiple Doses (14-days))
- Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours Postdose(Single and Multiple Doses (14-days))
- Time to Reach Maximum Plasma Concentration (Tmax)(Single and Multiple Doses (14-days))
- Long-term Adverse Events, Changes in Laboratory Parameters(up to 60 months)