Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
240
Countries
7
Sites
35
Invasive Candidiasis/ Candidemia
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]).
Key facts
- Sponsor
- Scynexis Inc.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Bacterial Infections and Mycoses [C01]
- Trial duration
- 23 Dec 2022 → 16 Dec 2025
- Decision date (initial)
- 2024-06-21
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- SCYNEXIS, Inc.
External identifiers
- EU CT number
- 2024-511755-18-00
- EudraCT number
- 2022-000648-32
- WHO UTN
- U1111-1305-0625
- ClinicalTrials.gov
- NCT05178862
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Pharmacokinetic, Therapy
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]).
Secondary objectives 4
- Key Secondary Objective: To demonstrate that treatment of Invasive Candidiasis/Candidemia with IV echinocandin followed by oral ibrexafungerp is non-inferior to IV echinocandin followed by oral fluconazole (or BAT), based on Global Response (clinical, radiological, and mycological response, as confirmed by the Data Review Committee [DRC]) at Day 14.
- To compare the efficacy of the treatment regimens, based on: Global Response at Day 30 and End of Therapy (EOT) as determined by the PI and DRC, Clinical Response as determined by the PI and DRC, Mycological Response as determined by the DRC, no recurrence as determined by the DRC, and fungal-free survival as determined by the DRC.
- To evaluate the safety of the regimens.
- To evaluate the pharmacokinetics (PK) of ibrexafungerp.
Conditions and MedDRA coding
Invasive Candidiasis/ Candidemia
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10060573 | Candidemia | 10021881 |
| 20.0 | LLT | 10064954 | Invasive candidiasis | 10021881 |
Study design 4 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | SOC IV echinocandin (open-label) Subjects will start with IV echinocandin given in an open-label fashion. Subjects will receive IV echinocandin treatment until the criteria for switching to oral antifungal treatment are met. Screening for the trial may occur after subject has begun IV echinocandin.
|
Not Applicable | None | ||
| 2 | Treatment phase (IV + oral step-down) The Screening and randomization visit can occur before the start of IV echinocandin treatment, or whilst the subject is already receiving echinocandin treatment. Subjects will be randomized to one of two treatment regimens.
|
Randomised Controlled | Double | [{"id":139961,"code":1,"name":"Subject"},{"id":139959,"code":3,"name":"Monitor"},{"id":139962,"code":5,"name":"Carer"},{"id":139958,"code":4,"name":"Analyst"},{"id":139960,"code":2,"name":"Investigator"}] | Ibrexafungerp regimen: IV echinocandin followed by ibrexafungerp + placebo matching fluconazole Fluconazole regimen: IV echinocandin followed by fluconazole + placebo matching ibrexafungerp |
| 3 | Oral step-down (open-label) Discontinuation from the double-blinded arm and transfer to the open-label arm according to the original randomization schedule in case fungal isolates will be identified as fluconazole non-susceptible.
|
Not Applicable | None | Open-label ibrexafungerp: Initial randomization to IV echinocandin followed by oral ibrexafungerp. Open-label best available therapy (BAT): Initial randomization to IV echinocandin followed by oral fluconazole. |
|
| 4 | Follow-up 2-Week Follow-up (FU) visit (14 days after EOT) and a 6-Week FU visit (42 days after EOT)
|
Not Applicable | None |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- Yes
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 2
- Subject is a male or female adult ≥ 18 years of age on the day the study informed consent is signed.
- Subject has a diagnosis of candidemia and/or invasive candidiasis, defined as evidence of Candida spp. in either a bloodstream or tissue/fluid culture from a normally sterile site (excluding eye, cardiac tissue, bone tissue, central nervous system or prosthetic device) collected ± 4 days (96 hours) of initiation of IV echinocandin accompanied by any related clinical sign and/or symptom (e.g., fever [on one occasion > 38°C], hypotension, or local signs of inflammation, etc.).
Exclusion criteria 5
- 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.
- Subject has abnormal liver test parameters: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 10-fold the upper limit of normal (ULN).
- Subject has severe hepatic impairment due to a history of chronic cirrhosis (Child-Pugh score > 9).
- 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.
- Baseline QTcF ≥ 500 msec, history or family history of Torsades de Pointes or other conditions that would put the subject at undue risk for development of ventricular arrythmias (including Torsades de Pointes).
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- All-cause Mortality (ACM) at Day 30 in the ITT population. The percentage of subjects with Successful Global Response, as determined by the DRC at EOT (European Union [EU] only).
Secondary endpoints 8
- Key secondary endpoint: The percentage of subjects with Successful Global Response, as determined by the DRC (based on clinical response as determined by the PI, mycological response and radiological response [when applicable]) at Day 14.
- Efficacy Endpoints: The percentage of subjects with Successful Global Response at Day 30 and EOT as determined by the PI and the DRC.
- Efficacy Endpoints: The percentage of subjects with Successful Clinical Response at Day 14, Day 30 and EOT as determined by the PI and the DRC.
- Efficacy Endpoints: The percentage of subjects with Successful Mycological Response at Day 14, Day 30 and EOT as determined by the DRC.
- Efficacy Endpoints: The percentage of subjects with no recurrence at 2 weeks and 6 weeks after EOT as determined by the DRC.
- Efficacy Endpoints: The percentage of subjects alive with Successful Global Response at EOT and no recurrence at 6 weeks after EOT as determined by the DRC.
- Safety Endpoints: Frequency of treatment-emergent adverse events (TEAEs), drug-related adverse events, discontinuations due to AEs, serious adverse events (SAEs), and safety laboratory assessments.
- PK Endpoint: Description of ibrexafungerp plasma concentrations.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD7557557 · Product
- Active substance
- Ibrexafungerp
- Other product name
- SCY-078
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 1500 mg milligram(s)
- Max total dose
- 1500 mg milligram(s)
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Not Authorised
- ATC code
- J02AX — OTHER ANTIMYCOTICS FOR SYSTEMIC USE
- MA holder
- SCYNEXIS, INC.
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EMA/OD/0000064849
Comparator 7
Fluconazol-GRY 200 mg Hartkapseln
PRD502244 · Product
- Active substance
- Fluconazole
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Max daily dose
- 800 mg milligram(s)
- Max total dose
- 800 mg milligram(s)
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- J02AC01 — FLUCONAZOLE
- Marketing authorisation
- 56728.03.00
- MA holder
- TEVA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Film-coating
SCP1086356 · ATC
- Active substance
- Clotrimazole
- Route of administration
- ORAL USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- J02AC01 — FLUCONAZOLE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fluconazole TEVA 200 mg harde capsules
PRD12384750 · Product
- Active substance
- Fluconazole
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Max daily dose
- 800 mg milligram(s)
- Max total dose
- 800 mg milligram(s)
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- J02AC01 — FLUCONAZOLE
- Marketing authorisation
- BE254186
- MA holder
- TEVA PHARMA BELGIUM N.V./S.A
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Film-coating
SCP13272866 · ATC
- Active substance
- Voriconazole
- Route of administration
- ORAL USE
- Max daily dose
- 800 mg milligram(s)
- Max total dose
- 800 mg milligram(s)
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- J02AC03 — VORICONAZOLE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP30340509 · ATC
- Active substance
- Anidulafungin
- Substance synonyms
- V-ECHINOCANDIN
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg/ml milligram(s)/millilitre
- Max total dose
- 00 mg/ml milligram(s)/millilitre
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- J02AX06 — ANIDULAFUNGIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP13251284 · ATC
- Active substance
- Caspofungin Acetate
- Substance synonyms
- Caspofungin diacetate
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg/ml milligram(s)/millilitre
- Max total dose
- 00 mg/ml milligram(s)/millilitre
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- J02AX04 — CASPOFUNGIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP15540542 · ATC
- Active substance
- Micafungin
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg/ml milligram(s)/millilitre
- Max total dose
- 00 mg/ml milligram(s)/millilitre
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- J02AX05 — MICAFUNGIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 2
Placebo for fluconazole 200 mg (capsule)
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Placebo for ibrexafungerp 250 mg (tablet)
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Scynexis Inc.
- Sponsor organisation
- Scynexis Inc.
- Address
- 1 Evertrust Plaza Floor 13th
- City
- Jersey City
- Postcode
- 07302-3051
- Country
- United States
Scientific contact point
- Organisation
- Scynexis Inc.
- Contact name
- David Angulo
Public contact point
- Organisation
- Scynexis Inc.
- Contact name
- Clincial Operations
Third parties 9
| Organisation | City, country | Duties |
|---|---|---|
| Psi CRO Greece ORG-100047165
|
Athens, Greece | On site monitoring, Code 10, Code 11, Code 12, Code 2, Code 5, Data management |
| Eurofins Central Laboratory B.V. ORG-100036990
|
Breda, Netherlands | Other, Laboratory analysis |
| Psi Cro AG ORG-100034251
|
Zug, Switzerland | On site monitoring, Code 10, Code 11, Code 12, Code 2, Code 5, Data management |
| Awinsa Life Sciences Private Limited ORG-100051075
|
New Delhi, India | Code 8 |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Keystone Bioanalytical Inc. ORG-100048363
|
North Wales, United States | Other |
| Perceptive Eclinical Limited ORG-100041144
|
Nottingham, United Kingdom | Interactive response technologies (IRT) |
| Jones Microbiology Institute Inc. ORG-100043091
|
North Liberty, United States | Other |
| CluePoints ORG-100050007
|
Ottignies-Louvain-La-Neuve, Belgium | Other |
Locations
7 EU/EEA countries · 35 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ended | 6 | 4 |
| Bulgaria | Ended | 7 | 3 |
| France | Ended | 8 | 4 |
| Germany | Ended | 14 | 6 |
| Greece | Ended | 13 | 5 |
| Italy | Ended | 7 | 4 |
| Spain | Ended | 17 | 9 |
| Rest of world
India, Turkey, Israel, Thailand, Korea, Republic of, South Africa, China, United States, Canada
|
— | 168 | — |
Investigational sites
Cliniques Universitaires Saint-Luc
Internal Medicine, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe
Universitair Ziekenhuis Gent
Internal Medicine, Corneel Heymanslaan 10, 9000, Gent
UZ Leuven
Internal Medicine, Herestraat 49, 3000, Leuven
Onze-Lieve-Vrouwziekenhuis
Internal Medicine, Moorselbaan 164, 9300, Aalst
University Multiprofile Hospital For Active Treatment Eurohospital Plovdiv Ltd.
Department of Surgery, Ulitsa Komatevsko Shose 79, 4004, Plovdiv
University Multiprofile Hospital For Active Treatment And Emergency Medicine N I Pirogov
Clinic of Purulent-Septic Surgery, Krasno Selo, Bulevard Gen Totleben 21, Sofiya
Umbal - Prof. D-R Stoyan Kirkovich AD
Clinic of Anesthesiology and Intensive Care, Ulitsa General Stoletov 2, 6003, Stara Zagora
Hopital Saint Louis
Infectious and Tropical Diseases, 1 Avenue Claude Vellefaux, 75010, Paris
Assistance Publique Hopitaux De Paris
InIntensive medicine and resuscitation, 27 Rue Du Faubourg Saint Jacques, 75014, Paris
Centre Hospitalier Universitaire De Nantes
Infectious and Tropical Diseases, 1 Place Alexis Ricordeau, 44000, Nantes
Centre Hospitalier Victor Dupouy
Multipurpose Resuscitation and continuous monitoring, 69 Rue Du Lieutenant Colonel Prudhon, 95107, Argenteuil Cedex
Helios Universitaetsklinikum Wuppertal
Haematology, oncology, clinical infectiology and palliative medicine, Heusnerstrasse 40, Barmen, Wuppertal
University Hospital Cologne AöR
Department of Internal Medicine I, Kerpener Strasse 62, Lindenthal, Cologne
Universitaetsklinikum Jena KöR
Institute for Infectious Diseases and Infection Control, Am Klinikum 1, Lobeda, Jena
Universitaetsklinikum Wuerzburg AöR
Medical Clinic and Polyclinic II, Oberduerrbacher Strasse 6, Grombuehl, Wuerzburg
Goethe University Frankfurt
Central Inner Medicine II, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
Medical Center - University Of Freiburg
Department of Internal Medicine, Hugstetter Strasse 55, Stuehlinger, Freiburg Im Breisgau
Laiko General Hospital Of Athens
Infectious Disease Unit of the University Department of Pathophysiology, Agiou Thoma (goudi) 17, 115 27, Athens
Evangelismos S.A.
1st Department of Critical Care, Ipsiladou 45-47, 106 76, Athens
Ippokratio General Hospital Of Thessaloniki
3rd University Clinic of Paediatrics, Konstadinoupoleos 49, 546 42, Thessaloniki
Evangelismos S.A.
5th Internal Medicine and Infectious Diseases Unit, Ipsiladou 45-47, 106 76, Athens
University General Hospital Attikon
4th University Department of Internal Medicine, Rimini Street 1, 124 62, Athens
ASST Grande Ospedale Metropolitano Niguarda
Infectious Disease Department, Piazza Dell'ospedale Maggiore 3, 20162, Milan
Azienda Sanitaria Universitaria Friuli Centrale
Infectious Disease Clinic, Via Pozzuolo 330, 33100, Udine
Azienda Ospedaliero Universitaria Di Modena
Complex Structure of Infectious Disease, Largo Del Pozzo 71, 41124, Modena
IRCCS Ospedale Policlinico San Martino
Infectious Disease Division, Largo Rosanna Benzi 10, 16132, Genoa
Hospital Universitario Virgen De La Macarena
Clinical Unit of Infectious Diseases, Clinical Microbiology and Preventive Medicine, Avenida Del Doctor Fedriani 3, 41009, Sevilla
Hospital Universitario Ramon Y Cajal
Infectious Disease, Carretera Del Colmenar Viejo Km 9 100, Por El Pardo, Madrid
Hospital Universitario De La Princesa
Infectious Disease, Calle De Diego De Leon 62, 28006, Madrid
Hospital General Universitario Gregorio Maranon
Microbiology Department, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Universitario Puerta De Hierro De Majadahonda
Infectious Disease Unit, Calle De Manuel De Falla 1, 28222, Majadahonda
Hospital Clinico Universitario De Valencia
Hematology Service and Hemotherapy Service, Avenida Blasco Ibanez 17, 46010, Valencia
Hospital Universitario Y Politecnico La Fe
Hematology, Avenida De Fernando Abril Martorell 106, 46026, Valencia
Hospital Clinic De Barcelona
Infectious Disease Department, Calle Villarroel 170, 08036, Barcelona
Hospital Del Mar
Infectious Disease Unit, Passeig Maritim De La Barceloneta 25-29, 08003, Barcelona
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2023-02-16 | 2023-03-07 | |||
| Bulgaria | 2023-01-13 | 2023-08-30 | |||
| France | 2023-05-04 | 2023-08-16 | |||
| Germany | 2023-04-20 | 2023-05-31 | |||
| Greece | 2022-12-23 | 2023-02-14 | |||
| Italy | 2023-04-11 | ||||
| Spain | 2023-03-02 | 2023-07-06 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 7 · Art. 38 CTR
Temporary halt TH-36165
- Halt date
- 2023-09-22
- Member states concerned
- Spain
- Publication date
- 2024-07-22
- Reason
- Medicinal Product related
- Explanation
- The trial was suspended on 22 September 2023 upon identification of a potential risk of cross-contamination of ibrexafungerp citrate drug substance with a non-antibacterial beta lactam drug substance at the manufacturing facility.
Identified risk of potential cross-contamination of ibrexafungerp citrate drug substance at the active ingredient manufacturing facility, with a non-antibacterial beta lactam drug substance, which is manufactured using equipment common to the manufacture of ibrexafungerp. Current regulatory guidance recommends segregation of beta lactam manufacturing compounds to avoid the potential of cross contamination to other compounds. Because non-antibacterial beta lactam products have the potential to sensitize patients to a future hypersensitivity reaction to beta-lactams as well as the potential to cause acute allergic reactions (hypersensitivity, including severe and life-threatening hypersensitivities) in certain patients, in an abundance of caution, the Sponsor has decided to pause all studies and new patient enrollment in ibrexafungerp clinical trials. - Follow-up measures
- Patients who were receiving treatment under the study were asked to stop taking blinded oral study drug or unblinded ibrexafungerp immediately and were switched to their best available therapy option for the continuation of the antifungal treatment.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-36154
- Halt date
- 2023-09-22
- Member states concerned
- Belgium
- Publication date
- 2024-07-22
- Reason
- Medicinal Product related
- Explanation
- The trial was suspended on 22 September 2023 upon identification of a potential risk of cross-contamination of ibrexafungerp citrate drug substance with a non-antibacterial beta lactam drug substance at the manufacturing facility.
Identified risk of potential cross-contamination of ibrexafungerp citrate drug substance at the active ingredient manufacturing facility, with a non-antibacterial beta lactam drug substance, which is manufactured using equipment common to the manufacture of ibrexafungerp. Current regulatory guidance recommends segregation of beta lactam manufacturing compounds to avoid the potential of cross contamination to other compounds. Because non-antibacterial beta lactam products have the potential to sensitize patients to a future hypersensitivity reaction to beta-lactams as well as the potential to cause acute allergic reactions (hypersensitivity, including severe and life-threatening hypersensitivities) in certain patients, in an abundance of caution, the Sponsor has decided to pause all studies and new patient enrollment in ibrexafungerp clinical trials. - Follow-up measures
- Patients who were receiving treatment under the study were asked to stop taking blinded oral study drug or unblinded ibrexafungerp immediately and were switched to their best available therapy option for the continuation of the antifungal treatment.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-36156
- Halt date
- 2023-09-22
- Member states concerned
- Bulgaria
- Publication date
- 2024-07-22
- Reason
- Medicinal Product related
- Explanation
- The trial was suspended on 22 September 2023 upon identification of a potential risk of cross-contamination of ibrexafungerp citrate drug substance with a non-antibacterial beta lactam drug substance at the manufacturing facility.
Identified risk of potential cross-contamination of ibrexafungerp citrate drug substance at the active ingredient manufacturing facility, with a non-antibacterial beta lactam drug substance, which is manufactured using equipment common to the manufacture of ibrexafungerp. Current regulatory guidance recommends segregation of beta lactam manufacturing compounds to avoid the potential of cross contamination to other compounds. Because non-antibacterial beta lactam products have the potential to sensitize patients to a future hypersensitivity reaction to beta-lactams as well as the potential to cause acute allergic reactions (hypersensitivity, including severe and life-threatening hypersensitivities) in certain patients, in an abundance of caution, the Sponsor has decided to pause all studies and new patient enrollment in ibrexafungerp clinical trials. - Follow-up measures
- Patients who were receiving treatment under the study were asked to stop taking blinded oral study drug or unblinded ibrexafungerp immediately and were switched to their best available therapy option for the continuation of the antifungal treatment.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-36162
- Halt date
- 2023-09-22
- Member states concerned
- Greece
- Publication date
- 2024-07-22
- Reason
- Medicinal Product related
- Explanation
- The trial was suspended on 22 September 2023 upon identification of a potential risk of cross-contamination of ibrexafungerp citrate drug substance with a non-antibacterial beta lactam drug substance at the manufacturing facility.
Identified risk of potential cross-contamination of ibrexafungerp citrate drug substance at the active ingredient manufacturing facility, with a non-antibacterial beta lactam drug substance, which is manufactured using equipment common to the manufacture of ibrexafungerp. Current regulatory guidance recommends segregation of beta lactam manufacturing compounds to avoid the potential of cross contamination to other compounds. Because non-antibacterial beta lactam products have the potential to sensitize patients to a future hypersensitivity reaction to beta-lactams as well as the potential to cause acute allergic reactions (hypersensitivity, including severe and life-threatening hypersensitivities) in certain patients, in an abundance of caution, the Sponsor has decided to pause all studies and new patient enrollment in ibrexafungerp clinical trials. - Follow-up measures
- Patients who were receiving treatment under the study were asked to stop taking blinded oral study drug or unblinded ibrexafungerp immediately and were switched to their best available therapy option for the continuation of the antifungal treatment.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-36164
- Halt date
- 2023-09-22
- Member states concerned
- Italy
- Publication date
- 2024-07-22
- Reason
- Medicinal Product related
- Explanation
- The trial was suspended on 22 September 2023 upon identification of a potential risk of cross-contamination of ibrexafungerp citrate drug substance with a non-antibacterial beta lactam drug substance at the manufacturing facility.
Identified risk of potential cross-contamination of ibrexafungerp citrate drug substance at the active ingredient manufacturing facility, with a non-antibacterial beta lactam drug substance, which is manufactured using equipment common to the manufacture of ibrexafungerp. Current regulatory guidance recommends segregation of beta lactam manufacturing compounds to avoid the potential of cross contamination to other compounds. Because non-antibacterial beta lactam products have the potential to sensitize patients to a future hypersensitivity reaction to beta-lactams as well as the potential to cause acute allergic reactions (hypersensitivity, including severe and life-threatening hypersensitivities) in certain patients, in an abundance of caution, the Sponsor has decided to pause all studies and new patient enrollment in ibrexafungerp clinical trials. - Follow-up measures
- Patients who were receiving treatment under the study were asked to stop taking blinded oral study drug or unblinded ibrexafungerp immediately and were switched to their best available therapy option for the continuation of the antifungal treatment.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-36160
- Halt date
- 2023-09-22
- Member states concerned
- Germany
- Publication date
- 2024-07-22
- Reason
- Medicinal Product related
- Explanation
- The trial was suspended on 22 September 2023 upon identification of a potential risk of cross-contamination of ibrexafungerp citrate drug substance with a non-antibacterial beta lactam drug substance at the manufacturing facility.
Identified risk of potential cross-contamination of ibrexafungerp citrate drug substance at the active ingredient manufacturing facility, with a non-antibacterial beta lactam drug substance, which is manufactured using equipment common to the manufacture of ibrexafungerp. Current regulatory guidance recommends segregation of beta lactam manufacturing compounds to avoid the potential of cross contamination to other compounds. Because non-antibacterial beta lactam products have the potential to sensitize patients to a future hypersensitivity reaction to beta-lactams as well as the potential to cause acute allergic reactions (hypersensitivity, including severe and life-threatening hypersensitivities) in certain patients, in an abundance of caution, the Sponsor has decided to pause all studies and new patient enrollment in ibrexafungerp clinical trials. - Follow-up measures
- Patients who were receiving treatment under the study were asked to stop taking blinded oral study drug or unblinded ibrexafungerp immediately and were switched to their best available therapy option for the continuation of the antifungal treatment.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-36158
- Halt date
- 2023-09-22
- Member states concerned
- France
- Publication date
- 2024-07-22
- Reason
- Medicinal Product related
- Explanation
- The trial was suspended on 22 September 2023 upon identification of a potential risk of cross-contamination of ibrexafungerp citrate drug substance with a non-antibacterial beta lactam drug substance at the manufacturing facility.
Identified risk of potential cross-contamination of ibrexafungerp citrate drug substance at the active ingredient manufacturing facility, with a non-antibacterial beta lactam drug substance, which is manufactured using equipment common to the manufacture of ibrexafungerp. Current regulatory guidance recommends segregation of beta lactam manufacturing compounds to avoid the potential of cross contamination to other compounds. Because non-antibacterial beta lactam products have the potential to sensitize patients to a future hypersensitivity reaction to beta-lactams as well as the potential to cause acute allergic reactions (hypersensitivity, including severe and life-threatening hypersensitivities) in certain patients, in an abundance of caution, the Sponsor has decided to pause all studies and new patient enrollment in ibrexafungerp clinical trials. - Follow-up measures
- Patients who were receiving treatment under the study were asked to stop taking blinded oral study drug or unblinded ibrexafungerp immediately and were switched to their best available therapy option for the continuation of the antifungal treatment.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| Scientific Summary of Clinical Trial Results SUM-135994
|
2026-05-26T16:53:15 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Lay Person Summary of Results | 2026-05-26T16:53:30 | Submitted | Laypersons Summary of Results |
Documents 63 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Lay Person Summary of Results_BG | N/A |
| Laypersons summary of results (for publication) | Lay Person Summary of Results_DE | N/A |
| Laypersons summary of results (for publication) | Lay Person Summary of Results_EN | N/A |
| Laypersons summary of results (for publication) | Lay Person Summary of Results_ES | N/A |
| Laypersons summary of results (for publication) | Lay Person Summary of Results_FR-BE | N/A |
| Laypersons summary of results (for publication) | Lay Person Summary of Results_GR | N/A |
| Laypersons summary of results (for publication) | Lay Person Summary of Results_IT | N/A |
| Laypersons summary of results (for publication) | Lay Person Summary of Results_NL-BE | N/A |
| Protocol (for publication) | D1_Protocol 2024-511755-18_Redacted | 4.0 |
| Protocol (for publication) | D1_Protocol GR_2024-511755-18_GR_Redacted | 4.0 |
| Protocol (for publication) | D1_Total Enrollment Statement_Redacted | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | N/A |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | N/A |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | N/A |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | N/A |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_EN_public | NA |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_BE-FR_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_BE-NL_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_Redacted | 4.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_Redacted | 4.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_Redacted | 3.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Future Research_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnancy FU_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnancy_BE-FR_redacted | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnancy_BE-NL_redacted | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant partner_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant partner_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_Redacted | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_redacted | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_Redacted | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_ Pregnant Partner_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_ Pregnant Partner_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_TC | 4.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_TC | 4.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner_TC | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner_TC | 2.0 |
| Subject information and informed consent form (for publication) | L2_Master Patient Instructions_Placeholder for publication | N/A |
| Subject information and informed consent form (for publication) | L2_Other subject information_GP Letter_public | 3.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information_Patient Reimbursement Statement_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information_PIS use of personal data_redacted | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Anidulafungin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Caspofungin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Fluconazole_Teva_Belgium | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Fluconazole_Teva_Germany | 5 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Micafungin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Voricanazole | 1 |
| Summary of results (for publication) | Summary of Results | N/A |
| Synopsis of the protocol (for publication) | D1_Synopsis for laypersons_BE-DE_DE_2024-511755-18 | N/A |
| Synopsis of the protocol (for publication) | D1_Synopsis for laypersons_BE-FR_2024-511755-18 | N/A |
| Synopsis of the protocol (for publication) | D1_Synopsis for laypersons_BE-NL_2024-511755-18 | N/A |
| Synopsis of the protocol (for publication) | D1_Synopsis for laypersons_BG_2024-511755-18 | N/A |
| Synopsis of the protocol (for publication) | D1_Synopsis for laypersons_EN_2024-511755-18 | N/A |
| Synopsis of the protocol (for publication) | D1_Synopsis for laypersons_ES_2024-511755-18 | N/A |
| Synopsis of the protocol (for publication) | D1_Synopsis for laypersons_FR_2024-511755-18 | N/A |
| Synopsis of the protocol (for publication) | D1_Synopsis for laypersons_GR_2024-511755-18 | N/A |
| Synopsis of the protocol (for publication) | D1_Synopsis for laypersons_IT_2024-511755-18 | N/A |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-05-13 | Germany | Acceptable 2024-06-19
|
2024-06-19 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-06-16 | Germany | Acceptable 2025-08-28
|
2025-08-28 |