| CTRI Number |
CTRI/2023/07/055764 [Registered on: 27/07/2023] Trial Registered Prospectively |
| Last Modified On: |
17/01/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A Phase 3, Randomized, double-blind study for Patients with Invasive Candidiasis treated With IV Echinocandin followed by either oral Ibrexafungerp or oral fluconazole |
|
Scientific Title of Study
|
A Phase 3, Multicenter, Prospective, Randomized, Double-blind Study of Two Treatment Regimens for Candidemia and/or Invasive Candidiasis: Intravenous Echinocandin followed by Oral Ibrexafungerp versus Intravenous Echinocandin followed by Oral Fluconazole |
| Trial Acronym |
MARIO |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2017-000381-29 |
EudraCT |
| NCT03059992 |
ClinicalTrials.gov |
| SCY-078-302 Protocol Version 2.1 24 Nov 2022 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Radhika Bobba |
| Designation |
Regional Director, India and Far East |
| Affiliation |
PSI CRO Pharma India Pvt Ltd |
| Address |
PSI CRO Pharma India Pvt Ltd, 414 Shree complex, 73, St Johns
Road, Bangalore, India- 560042
Bangalore
KARNATAKA
560042
India |
| Phone |
0 |
| Fax |
|
| Email |
Radhika.Bobba@psi-cro.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Radhika Bobba |
| Designation |
Regional Director, India and Far East |
| Affiliation |
PSI CRO Pharma India Pvt Ltd |
| Address |
PSI CRO Pharma India Pvt Ltd, 414 Shree complex, 73, St Johns
Road, Bangalore, India- 560042
Bangalore
KARNATAKA
560042
India |
| Phone |
0 |
| Fax |
|
| Email |
Radhika.Bobba@psi-cro.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Radhika Bobba |
| Designation |
Regional Director, India and Far East |
| Affiliation |
PSI CRO Pharma India Pvt Ltd |
| Address |
PSI CRO Pharma India Pvt Ltd, 414 Shree complex, 73, St Johns
Road, Bangalore, India- 560042
Bangalore
KARNATAKA
560042
India |
| Phone |
0 |
| Fax |
|
| Email |
Radhika.Bobba@psi-cro.com |
|
|
Source of Monetary or Material Support
|
| SCYNEXIS, Inc.
1 Evertrust Plaza, 13th Floor Jersey City, NJ 07302, USA |
|
|
Primary Sponsor
|
| Name |
PSI CRO Pharma India Pvt Ltd |
| Address |
414 Shree complex, 73, St Johns Road, Bangalore, India- 560042 |
| Type of Sponsor |
Contract research organization |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Belgium
Bulgaria
Canada
China
France
Germany
Greece
India
Israel
Italy
Republic of Korea
South Africa
Spain
United States of America
Taiwan
Thailand
Turkey |
|
Sites of Study
|
| No of Sites = 7 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr D Suresh Kumar |
Apollo Specialty Hospitals |
No.64, OFF P.H Road,
Vanagaram to Ambattur
main road,
Ayanambakkam, Chennai-
600095, India
Chennai
TAMIL NADU |
9128296784
dskinfdis@gmail.com |
| Dr Shaik Abdul Rafi |
Care Hospitals |
6-3-248/2, Road no:1, Banjara Hills,
Hyderabad, Telangana-
500034
Hyderabad
TELANGANA |
9052101289
Rafipulm@gmail.com |
| Dr Manish Gupta |
Max Super Speciality |
Hospital W-3, Sector-1,
Vaishali, Ghaziabad, Uttar
Pradesh 201012
Ghaziabad
UTTAR PRADESH |
9868081770
Manish.Gupta@maxhealthcare.com |
| Dr Deven Juneja |
Max Super Speciality Hospital |
1, Press Enclave Road,
Saket, New Delhi, Delhi
110017
New Delhi
DELHI |
98188290380
deven.juneja@maxhealthcare.com |
| Dr Vikas Suri |
Post Graduate Institute of Medical Education and Research |
Madhya Marg, Sector 12,
Chandigarh-160012
Chandigarh
CHANDIGARH |
7087009683
surivikas9479@gmail.com |
| Dr Shashikant Janardan Apte |
Sahyadri Super Speciality Hospital |
Speciality Hospital,
Plot No. 30-C,
Erandwane, Karve
Road, Deccan
Gymkhana, Pune -
411004, Maharashtra,
India
Pune
MAHARASHTRA |
9822404983
shashikant.apte@gmail.com |
| Dr Atul Gogia |
Sir Ganga Ram Hospital |
SGRH Marg, Rajinder
Nagar New Delhi, Delhi-
110060
New Delhi
DELHI |
9891003450
atulgogs@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 7 |
| Name of Committee |
Approval Status |
| CARE Hospitals Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee, Max Super Speciality Hospital, |
Approved |
| Institutional Ethics Committee, Post Graduate Institute of Medical Education and Research |
Submittted/Under Review |
| Institutional Ethics Committee-Clinical Studies Apollo Hospitals Enterprises Limited |
Submittted/Under Review |
| Max Healthcare Ethics Committee |
Approved |
| Sahyadri Hospitals Private Ltd. Ethics Committee |
Approved |
| Sir Ganga Ram Hospital Ethics Committee |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B379||Candidiasis, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Fluconazole Placebo |
Loading Dose- Day1 800mg,BID
Maintenance Period- Day2 400 mg, BID
Maintenance Period- Day3 to EOT 400 mg, QD |
| Intervention |
Ibrexafungerp |
Loading Dose Period: Oral 750 mg BID tablets, Maintenace Dose Period: Oral 750 mg QD |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1.Subject has any of the following forms of invasive candidiasis at Screening:
a.Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed).
b.Osteomyelitis.
c.Endocarditis or myocarditis.
d.Meningitis, endophthalmitis, or any central nervous system infection.
e.Chronic disseminated candidiasis.
f.Urinary tract candidiasis due to ascending Candida infection secondary to unresolved obstruction or non-removeable device in the urinary tract.
g.Patients with a sole diagnosis of mucocutaneous candidiasis, i.e., oropharyngeal, esophageal or genital candidiasis; or Candida lower urinary tract infection or Candida isolated solely from respiratory tract specimens.
h.Patients with concurrent invasive fungal infection other than Candida spp., e.g., cryptococcosis, mold infection or endemic fungal infection.
i.Patients who failed a previous antifungal therapy for the same infection.
j.Subject has an uncontrolled fungal disease source (e.g., indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained) that is likely to be the source of the candidemia or invasive candidiasis.
2.Subject has abnormal liver test parameters: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 10-fold the upper limit of normal (ULN).
3.Subject has severe hepatic impairment and a history of chronic cirrhosis (Child-Pugh score > 9).
4.Subject has received more than 48 hours of non-echinocandin antifungal therapy for the treatment of invasive candidiasis (including candidemia) within 96 hours preceding initiation of IV echinocandin.
Exception: Receipt of antifungal therapy to which any Candida spp. isolated in qualifying culture is not susceptible.
5.Patients with baseline QTcF ≥ 500 msec, history or family history of Torsades de Pointes or other conditions that would put the subject at undue risk of development of ventricular arrhythmias (including Torsades de Pointes).
6.Subject is receiving or anticipates to require treatment with the prohibited medications (including prescription and over-the-counter medications, supplements, and herbal products) listed in Section 20.1 (Appendix A).
7.Subject has a known history of allergy, hypersensitivity or serious reaction to ibrexafungerp, any of the azole or echinocandin class of antifungal or to any of the components of the formulations.
8.Subject has received treatment with ibrexafungerp in a previous invasive fungal infection trial.
9.Subject is currently participating in another interventional treatment trial with an investigational agent, has participated in any other investigational study within 30 days (or within 5.5 half-lives of the investigational product, whichever is longer) before signing the ICF, or is using an investigational device at the time of Screening.
10.Subject has any other condition or laboratory abnormality evidencing a major organ system disease that, in the judgment of the PI, would put the subject at unacceptable risk for participation in the study or may interfere with the assessments included in the study.
11.Subject is an employee of SCYNEXIS, Inc., the investigator or the Contract Research Organization involved in the study, or is an immediate family member (partner, offspring, parent, sibling, or sibling’s offspring) of an employee involved in the study.
12.Subject is unlikely to comply with protocol requirements.
13.Subject is expected to die from a non-infectious cause within 30 days from the day the study ICF is signed.
14.Subject is pregnant or breastfeeding or plans to become pregnant
|
|
| ExclusionCriteria |
| Details |
1.Subject has any of the following forms of invasive candidiasis at Screening:
a.Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed).
b.Osteomyelitis.
c.Endocarditis or myocarditis.
d.Meningitis, endophthalmitis, or any central nervous system infection.
e.Chronic disseminated candidiasis.
f.Urinary tract candidiasis due to ascending Candida infection secondary to unresolved obstruction or non-removeable device in the urinary tract.
g.Patients with a sole diagnosis of mucocutaneous candidiasis, i.e., oropharyngeal, esophageal or genital candidiasis; or Candida lower urinary tract infection or Candida isolated solely from respiratory tract specimens.
h.Patients with concurrent invasive fungal infection other than Candida spp., e.g., cryptococcosis, mold infection or endemic fungal infection.
i. Patients who failed a previous antifungal therapy for the same infection.
j. Subject has an uncontrolled fungal disease source (e.g., indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained) that is likely to be the source of the candidemia or invasive candidiasis.
2.Subject has abnormal liver test parameters: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 10-fold the upper limit of normal (ULN).
3.Subject has severe hepatic impairment and a history of chronic cirrhosis (Child-Pugh score > 9).
4.Subject has received more than 48 hours of non-echinocandin antifungal therapy for the treatment of invasive candidiasis (including candidemia) within 96 hours preceding initiation of IV echinocandin.
Exception: Receipt of antifungal therapy to which any Candida spp. isolated in qualifying culture is not susceptible.
5.Patients with baseline QTcF ≥ 500 msec, history or family history of Torsades de Pointes or other conditions that would put the subject at undue risk of development of ventricular arrhythmias (including Torsades de Pointes).
6.Subject is receiving or anticipates to require treatment with the prohibited medications (including prescription and over-the-counter medications, supplements, and herbal products) listed in Section 20.1 (Appendix A).
7.Subject has a known history of allergy, hypersensitivity or serious reaction to ibrexafungerp, any of the azole or echinocandin class of antifungal or to any of the components of the formulations.
8.Subject has received treatment with ibrexafungerp in a previous invasive fungal infection trial.
9. Subject is currently participating in another interventional treatment trial with an investigational agent, has participated in any other investigational study within 30 days (or within 5.5 half-lives of the investigational product, whichever is longer) before signing the ICF, or is using an investigational device at the time of Screening.
10. Subject has any other condition or laboratory abnormality evidencing a major organ system disease that, in the judgment of the PI, would put the subject at unacceptable risk for participation in the study or may interfere with the assessments included in the study.
11. Subject is an employee of SCYNEXIS, Inc., the investigator or the Contract Research Organization involved in the study, or is an immediate family member (partner, offspring, parent, sibling, or sibling’s offspring) of an employee involved in the study.
12. Subject is unlikely to comply with protocol requirements.
13. Subject is expected to die from a non-infectious cause within 30 days from the day the study ICF is signed.
14. Subject is pregnant or breastfeeding or plans to become pregnant
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| •To demonstrate that treatment of Invasive Candidiasis/ Candidemia with intravenous (IV) echinocandin followed by oral ibrexafungerp is non inferior to IV echinocandin followed by oral fluconazole (or Best Available Therapy [or BAT]). |
The primary endpoint of the study is ACM at Day 30 in the ITT population.
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Assessment of Recurrence of Baseline Fungal Infection.
Assessment of survival
|
The percentage of subjects with Successful Global Response, as determined by the DRC (Data Review Committee) at Day 14.
|
|
|
Target Sample Size
|
Total Sample Size="220"
Sample Size from India="25"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
08/08/2023 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
03/02/2023 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="3"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
This is a multicenter, open label, non-comparator, single arm study to evaluate the efficacy and safety of ibrexafungerp in patients ≥ 18 years of age with a documented invasive and/or severe fungal disease that has been intolerant or refractory (rIFI) to Standard of Care (SoC) antifungal treatment. Patients will be treated with ibrexafungerp for up to 180 days. Treatment beyond 180 days and combination therapy with other antifungal agents may be allowed under special circumstances to be agreed upon by the Investigator and the Sponsor. Subjects must have a proven or probable fungal disease and meet all study criteria to be considered for enrollment. Eligible subjects must also have documented evidence of failure of, intolerance to, or toxicity related to a currently approved SoC antifungal treatment. Subjects will also be considered for enrollment if they have an eligible fungal disease and, in the judgement of the investigator, the subject cannot receive approved oral antifungal options (e.g. susceptibility of the organism or risk for drug-drug interactions) and a continued IV antifungal therapy is not desirable or feasible due to clinical or logistical circumstance |