Study to Assess the Safety and Efficacy of Intravenous BSG005 in Patients With Invasive Fungal Infection

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

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.

Study Overview

• Status: Recruiting
• Conditions: Invasive Fungal Infection
• Intervention / Treatment: Drug: BSG005

Detailed Description

This study is an open-label, Phase 1b, dose-escalation/finding study to assess safety and efficacy of intravenous BSG005 in patients with uncomplicated invasive fungal infections (IFI).

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. Following 7 days of Screening period, patients will be enrolled in the study. In Cohort 1, patients will be administered with a dose of 0.1 mg/kg, which was tested in the single ascending dose (SAD) group of the Phase 1 healthy subject study and will follow an intra-patient dose-escalation step. Based on the overall health status of the patient (safety and efficacy of study intervention), the dose can be adjusted at any point of time according to the Investigator´s judgment, which would be based on clinical or mycological or radiological assessments dependent on the information available. This can be dose escalation or dose de-escalation as appropriate. During the Treatment period, there may be a pause of one day or more if deemed necessary by the Investigator. Each patient will be evaluated individually for efficacy and safety to decide if escalation is possible. The dose will be escalated by 0.1 mg/kg every 3 days or 1 day earlier (ie, 2 days) at the Investigator's discretion.

The starting dose in Cohort 1 will be 0.1 mg/kg for the first 3 days of treatment; 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 of 1.0 mg/kg or till a maximum of 28 days of treatment duration in Cohort 1, with the possibility to stop anytime after 14 days depending on the status of the patient. The starting dose of Cohort 2 will be decided by the Data Safety Review Committee (DSRC) after review of all available relevant data up to Day 14 of treatment for all patients in Cohort 1. Subsequently, a similar dose-escalation will be followed for Cohort 2 as defined above for Cohort 1. The dose can be escalated up to a maximum of 2.0 kg/mg. A similar process will be followed for the first dose in Cohort 3 and the dose can be escalated up to a maximum of 3.0 mg/kg. BSG005 will be administered daily via IV infusion for 120 minutes (may be prolonged for up to 240 minutes). As BSG005 has a propensity for phlebitis, central catheters or long peripheral catheters are preferred for infusion.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tine Olesen, CEO; Phone Number: +4531355707; Email: tine.olesen@biosergen.net
• Study Contact Backup: Name: Niels Laursen, CFO; Phone Number: +4540145059; Email: niels.laursen@biosergen.net

Study Locations

• India
  • Haryana
    • Dehli, Haryana, India, 121003
      • Recruiting
      • JSS Medical Research Asia Pacific Private Limited
      • Contact: Neeraj Prasad, Dr; Phone Number: +919930740633; Email: neeraj.prasad@jssresearch.com
      • Principal Investigator: Pawan Kumar Singh, Dr
      • Principal Investigator: Manoj Kumar, Dr
      • Principal Investigator: Ashish Ganjare, Dr
      • Principal Investigator: Richa Giri, Dr
      • Principal Investigator: Armit Dravid, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 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. 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

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

   1. Failure with one first-line agent, defined as either: Radiologic progression, Increase in serologic markers such as galactomannan antigen or beta-D-glucan, Failure of clearance of cultures , Progression or lack of improvement in a clinically appropriate timeframe of clinical symptoms attributed to IFI;
   2. Inability to tolerate AmB, as defined by at least one of the following: Nephrotoxicity with either: 1.5 mg/dL increase in creatinine from baseline, 50% increase in creatinine from baseline ii. Contraindication to use AmB with either:- Persistent hypokalemia or hypomagnesemia while on AmB despite appropriate electrolyte replacement
   3. Documented in vitro resistance to first-line antifungal therapy (ie fluconazole resistance in Candida auris)
   4. Treatment-limiting drug-drug interactions prohibiting the use of antifungals (azoles and echinocandins) such as concurrent rifampcin, rifabutin, phenytoin, carbamazepine, bedaqualine

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.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active treatment; The patient will receive active treatment in a dose escalation manner increasing the dose every 3 days dependent on safety and efficacy	Drug: BSG005; Single arm dose escalation in patients with invasive fungal infection; Other Names: Polyene Macrolide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To establish the safety and tolerability of BSG005 in patients with severe invasive fungal infection	Treatment Emergent Adverse Event (CTC grading of severity)	From enrollment to end of treamtent including 14 days follow up
To establish the safety and tolerability of BSG005 in patients with severe invasive fungal infection	Renal function (eGFR)	From enrollment to end of treamtent including 14 days follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the overall response to BSG005 treatment in patients with invasive fungal infection	Overall response as per guidelines (composite of clinical, radiology, microbiology) 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)	From treatment start to end of treatment plus 14 days follow up
To assess the overall response to BSG005 treatment in patients with invasive fungal	To guide dose selection for future testing	From treatment start to end of treatment plus 14 days follow up

Collaborators and Investigators

• Sponsor: Biosergen AS
• Collaborators: Alkem Laboratories Ltd; JSS Medical Research Asia pacific Private Limited
• Investigators: Study Chair: Tine Olesen, PhD, BIOSERGEN AB

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: August 29, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Actual): November 7, 2024

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Rescue therapy; Invasive fungal infection; BSG005; Polyene macrolide
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Invasive Fungal Infections; Infections; Communicable Diseases; Mycoses
• Other Study ID Numbers: BSG-1.02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Safety and efficacy data will be shared
• IPD Sharing Time Frame: The information will be available after end of study when the clinical trial report is written
• IPD Sharing Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact tine.olesen@biosergen.net
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No