A Phase 1b, Single Arm, Multi-center, Open-label, Dose-escalation Study to Assess the Safety and Efficacy of Intravenous BSG005 in Patients with Invasive Fungal Infection
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 9
- 主要终点
- To establish the safety and tolerability of BSG005 in patients with severe invasive fungal infection
研究概览
简要总结
This study is an open-label, Phase 1b, dose-escalation/finding study to assess the safety and efficacy of intravenous BSG005 in patients with uncomplicated invasive fungal infections (IFI).
Approximately 15 patients are planned to be enrolled in 3 cohorts.
The study will be conducted in 3 cohorts consisting of 3 periods, namely: Screening, Treatment, and Follow-up periods. In each cohort, 5 patients are planned to be enrolled.
This study is a single-arm study. The treatment (BSG005) in each dose level will be administered once daily for 3 days via IV infusion. If the safety and tolerability profiles are acceptable at each dose level, the patients will be treated for a maximum of 28 days. Each patient will be in the study for up to 50 days, which consists of a 7-day Screening period, 1 day for baseline assessments, up to 28 days (maximum) of treatment with BSG005, and 14 days of follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- All
入选标准
- •Age greater than 18 years.
- •Able to provide written informed consent or have a legally authorized representative that can provide informed consent in case of incapacitation.
- •Diagnosed by Investigator to have an IFI.Proven IFIs as defined in the 2020 consensus definitions by the European Organization for Research and Treatment of Cancer/ Mycoses Study Group Education and Research Consortium (EORTC/MSGERC).
- •Probable or possible IFIs can be included using the EORTC/MSGERC criteria or other established criteria.
- •Protocol Number: BSG-1.02 Biosergen AS Confidential Protocol Version 1.0 Page 16 The inclusion of patients with IFI caused by, eg, Aspergillus spp and Candida spp, is preferred as these species are generally known to be responsive to a lower dose than other species, eg, Mucor mycosis spp.
- •IFI patients with mild to moderate renal impairment or IFI patients requiring an alternative treatment as current treatment cannot be continued due to any of the following: a) Failure with one first-line agent, defined as either Radiologic progression or Increase in serologic markers such as galactomannan antigen or beta-D-glucan or Failure of clearance of cultures or Progression or lack of improvement in a clinically appropriate timeframe of clinical symptoms attributed to IFI.b) Inability to tolerate AmB, as defined by at least one of the following i.
- •Nephrotoxicity with either: 1.5 mg/dL increase in creatinine from baseline or 50% increase in creatinine from baseline ii.
- •Contraindication to use AmB with either:Persistent hypokalemia or hypomagnesemia while on AmB despite appropriate electrolyte replacement c) Documented in vitro resistance to first-line antifungal therapy (ie fluconazole resistance in Candida auris) d) Treatment-limiting drug-drug interactions prohibiting the use of antifungals (azoles and echinocandins) such as concurrent rifampcin, rifabutin, phenytoin, carbamazepine, bedaqualine, quetiapine and others according to the antifungal interactions database(https://www.antifungalinteractions.org) or the patient is on any treatment prohibiting the use of standard antifungal agent such as azoles, echinocandins, amphotericin B, etc
- •Patient requiring not more than 28 days of antifungal therapy as per Investigator opinion as per the institutional guidance.
排除标准
- •Patient has a known hypersensitivity or severe infusion-related reaction to any polyene drug.
- •Infection caused by a known or suspected organism with intrinsic resistance to AmB.
- •Concurrent use of another investigational agent within 30 days of enrollment.
- •Chronic kidney disease with estimated glomerular filtration rate (eGFR) less than 30 mL/min or dialysis.
- •Patients with acute kidney injury with eGFR less than 30 mL/min and improving creatinine level can be included as judged by the Investigator.
- •Note: Patients may be rescreened within 48 hours if laboratory values are found to be abnormal.
- •Has liver enzyme results (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) greater than 5 times the upper limit of normal.
- •Has a bilirubin level greater than 5 times the upper limit of normal.
- •Patients who have an ejection fraction less than 25% of predicted.
- •Currently pregnant or planning on getting pregnant while on study (details of contraception guidance are provided in Section 13).
- •Breastfeeding.
- •Patients not likely to survive a minimum of 28 days from start of screening.
- •Patient receiving prohibited medications.
- •Patient is an abuser of alcohol or medication.
- •Patient is unlikely to comply with protocol requirements.
- •Patients testing positive for HIV.
- •Patients with malignancy.
- •If participating in sexual activity that could lead to pregnancy, individuals of reproductive potential who can become pregnant must agree to use contraception throughout the study.
结局指标
主要结局
To establish the safety and tolerability of BSG005 in patients with severe invasive fungal infection
时间窗: Incidence and severity of TEAEs | Abnormal laboratory parameters, vital signs, electrocardiograms, and physical examinations | AESI | Time to recovery of baseline renal function in patients with elevated creatinine due to acute kidney injury or renal dysfunction separated into categories of transient and permanent diseases. The primary endpoint will be assessed on every dosing day from day 1 to day 29.
次要结局
- To assess the overall response integrating clinical, radiological, & mycological responses to BSG005 treatment in patients with IFI(To establish an effective clinical dose range of BSG005)
- To assess the pharmacokinetics of BSG005 at dose levels of 0.1mg/kg & at maximal tolerable dose in patients with IFI(Plasma pharmacokinetic parameters (at least):)
研究者
Dr Neeraj Prasad
JSS Medical Research Asia pacific Private Limit