CTRI/2024/04/066016 [Registered on: 19/04/2024] Trial Registered Prospectively
Last Modified On:
20/01/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
BSG005 in treatment of Patients with Invasive Fungal Infection
Scientific Title of Study
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
Trial Acronym
nil
Secondary IDs if Any
Secondary ID
Identifier
BSG-1.02, Version 1.0 dated 1 Dec 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Neeraj Prasad
Designation
Deputy Director – Operations
Affiliation
JSS Medical Research Asia pacific Private Limit
Address
Tower 2, 1st Floor, South Wing, L&T Business Park, Plot no 12/4, Sector 27 D, Delhi Mathura Road, Near Sarai Khawja Metro Station, Faridabad -121003, Haryana, India
Faridabad HARYANA 400080 India
Phone
9930740633
Fax
Email
neeraj.prasad@jssresearch.com
Details of Contact Person Scientific Query
Name
Dr Sonika Newar
Designation
General Manager Medical Monitoring and Safety
Affiliation
JSS Medical Research Asia pacific Private Limit
Address
Tower 2, 1st Floor, South Wing, L&T Business Park, Plot no 12/4, Sector 27 D, Delhi Mathura Road, Near Sarai Khawja Metro Station, Faridabad -121003, Haryana, India
Faridabad HARYANA 400080 India
Phone
8800799887
Fax
Email
sonika.newar@jssresearch.com
Details of Contact Person Public Query
Name
Dr Jayashri Krishnan
Designation
Vice President Operations
Affiliation
JSS Medical Research Asia pacific Private Limit
Address
Tower 2, 1st Floor, South Wing, L&T Business Park, Plot no 12/4, Sector 27 D, Delhi Mathura Road, Near Sarai Khawja Metro Station, Faridabad -121003, Haryana, India
Faridabad HARYANA 400080 India
Phone
9771407484
Fax
Email
jayashri.krishnan@jssresearch.com
Source of Monetary or Material Support
official Name-Biosergen AS, Vestre Rosten 81, Postal code 7 Country name- 7075 Tiller, 1601 Trondheim, Norway.
Primary Sponsor
Name
Biosergen AS
Address
Official Address-Vestre Rosten 81, Postal code & Name of the country- 7075 Tiller, 1601 Trondheim, Norway
All India Institute of Medical Sciences (AIIMS)
Room No. 8,
Porta-cabin,
Ansari Nagar, New Delhi – 110029, INDIA
Ansari Nagar, New Delhi – 110029, INDIA
New Delhi DELHI
9999597289
vijayhadda@yahoo.com
Dr Ashish Ganjare
Aureus Institute of Medical Sciences Pvt. Ltd., Nagpur
OPD No. 6, First Floor, Department of Critical Care Unit, Aureus Institute of Medical Sciences Pvt. Ltd.
Plat No. 16, Wanjari Nagar, Opp. Rajabaksha Hanuman Mandir,
Nagpur 440003
Maharashtra India
Nagpur MAHARASHTRA
9370659338
ashish6978@gmail.com
Dr M Manoj Kumar
BLIV Multispecialty Hospital, Nellore
1st Floor, room No: 201, B’LIV Hospital, A Unit of PCRI Hospitals pvt ltd, S2 Theatre Road,Opp. Anil Diabetes Center, Pogathota,
Nellore - 524001
Nellore ANDHRA PRADESH
9700487720
manojkumardec@gmail.com
Dr Richa Giri
GSVM Medical College, Kanpur
Room No .01, Ground floor, Postgraduate Department of Medicine G.S.V.M. Medical College Kanpur -208002 U.P. India Kanpur Nagar UTTAR PRADESH
8400331045
drrichagiri.gsvm@gmail.com
Dr Gautam Suresh
KLES Dr Prabhakar Kore Hospital and MRC
G+2 SMO Office, Clinical Research Department, KLES Dr Prabhakar Kore Hospital and MRC Nehru Nagar Belagavi, Karnataka, India- 590010 Belgaum KARNATAKA
9964854464
docgautam6787@gmail.com
Dr Jairaj Nair
Lokmanya Tilak Municipal Medical College and General Hospital (LTMMC & LTMGH), Sion
2nd floor, Department of Respiratory Medicine, LTMMC & LTMGH, Dr. Babasaheb Ambedkar Road, Sion, Mumbai - 400022 Mumbai MAHARASHTRA
8898816660
drjairajpnair@gmail.com
Dr Ameet Dravid
Noble hospital
Clinical Research Department, Anex Building, Ground Floor, Noble Hospital Pvt. Ltd., 153, Magarpatta City Road, Hadapsar, Pune-411013, Maharashtra, India Pune MAHARASHTRA
9975619766
ameet.dravid@gmail.com
Dr Ashish Bhalla
Post Graduate Institute Medical Education and research
Room number 10, faculty department, second floor, Nehru Hospital, Post Graduate Institute Medical Education and Research, Sector 12, Chandigarh-160012, India. Chandigarh CHANDIGARH
9417023973
bhalla.chd@gmail.com
Dr Pawan Kumar Singh
Pt. B. D. Sharma PGIMS Rohtak, Haryana, 124001, India
Department of PCCM,
Old Emergency Room No 17, Ground Floor. Rohtak HARYANA
Ethics Committee of Crescent Hospital Heart Centre, Dept. of Ethics Committee Ethics Committee of Crescent Hospital Heart Centre, Crescent Hospital And Heart Centre, Plot No 25, Behind Old Mount Carmel School, Near Lokmat Square, Dhantoli Nagpur Nagpur Maharashtra - 440012 India
Approved
GSVM Medical College, Kanpur
Approved
Institute Ethics Committee All India Institute of Medical Sciences Ansari Nagar, New Delhi-29 New Delhi
Approved
Institutional Ethics Committee Post Graduate Institute of Medical Education and Research Sector 12, Chandigarh-160012, India
Approved
Institutional Ethics Committee of KLE Academy of Higher Education and Research, JNMC Campus, KLEs Dr. Prabhakar Kore Hospital and MRC Nehru Nagar Belagavi, Karnataka, India- 590010
Approved
Institutional Ethics Committee, Lokmanya Tilak, Lokmanya Tilak Municipal Medical College, Dr. Babasaheb Ambedkar Road, Sion, Mumbai, Mumbai City, Maharashtra – 400022
Approved
Institutional Ethics Committee, Pt. BD Sharma, Post Graduate Institute of SciencePGIMS UHS Rohtak-124001
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 14 days of treatment (i.e., a maximum treatment period of 28 days).
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 1.0 mg/kg or till a maximum of 28 days of duration in Cohort 1, with the possibility to stop at 14 or 21 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.
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.
ExclusionCriteria
Details
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.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To establish the safety and tolerability of BSG005 in patients with severe invasive fungal infection
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 Outcome
Outcome
TimePoints
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
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 IFI
Total Sample Size="15" Sample Size from India="15" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
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.