Health Condition 1: B49- Unspecified mycosis
Conditions
Interventions
Intervention1: BSG005: BSG005 treatment duration once daily via IV infusion can be a minimum of 14 days. Patients with partial improvement or stable disease at 2 weeks should be offered an additional
if no safety concerns are experienced, the patients will be escalated up to 0.2 mg/kg. This process will be followed up to a maximum 1.0 mg/kg or till a maximum of 28 days of duration in Cohort 1, wit
Sponsors
Biosergen AS
Alkem Laboratories Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age greater than 18 years.2. Able to provide written informed consent or have a legally authorized representative that can provide informed consent in case of incapacitation.3. 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. 4. 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 5. Patient requiring not more than 28 days of antifungal therapy as per Investigator opinion as per the institutional guidance.
Exclusion criteria
Exclusion criteria: 1. Patient has a known hypersensitivity or severe infusion-related reaction to any polyene drug. 2. Infection caused by a known or suspected organism with intrinsic resistance to AmB. 3. Concurrent use of another investigational agent within 30 days of enrollment. 4. 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. 5. Has liver enzyme results (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) greater than 5 times the upper limit of normal. Note: Patients may be rescreened within 48 hours if laboratory values are found to be abnormal. 6. Has a bilirubin level greater than 5 times the upper limit of normal. Note: Patients may be rescreened within 48 hours if laboratory values are found to be abnormal. 7. Patients who have an ejection fraction less than 25% of predicted. 8. Currently pregnant or planning on getting pregnant while on study (details of contraception guidance are provided in Section 13). 9. Breastfeeding. 10. Patients not likely to survive a minimum of 28 days from start of screening. 11. Patient receiving prohibited medications. 12. Patient is an abuser of alcohol or medication. 13. Patient is unlikely to comply with protocol requirements. 14. Patients testing positive for HIV. 15. Patients with malignancy. 16. The Investigator is of the opinion the patient should not participate in the study. 17. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To establish the safety and tolerability of BSG005 in patients with severe invasive fungal infectionTimepoint: 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 Timepoint: Overall response integrating clinical, radiological, & mycological responses at Day 15 & Day 29 Treatment success – complete & partial response, & stabile disease Treatment failure - progression Dose estimation for treatment success based on fungal infection strain Mortality during the course of the study (crude & associated) ;To assess the pharmacokinetics of BSG005 at dose levels of 0.1mg/kg & at maximal tolerable dose in patients with IFITimepoint: Plasma pharmacokinetic parameters (at least): Cmax,ss, Cmaxss/Dose, tmax, AUCtau, AUC0-last, AUC0-last/Dose, t1/2, CLss, Vzss, Ctrough | — |
Countries
India
Contacts
Public ContactDr Jayashri Krishnan
JSS Medical Research Asia pacific Private Limit
Outcome results
None listed