Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Ended
Participants planned
40
Countries
2
Sites
6
Fungal infections
To evaluate the pharmacokinetics (PK) of a single IV dose of rezafungin in paediatric subjects from birth to <18 years, receiving concomitant systemic antifungals as prophylaxis for invasive fungal infection (IFI) or to treat a suspected or confirmed fungal infection
Key facts
- Sponsor
- Mundipharma Research Limited, Mundipharma Research Limited
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Bacterial Infections and Mycoses [C01]
- Trial duration
- 18 May 2023 → 14 Oct 2024
- Decision date (initial)
- 2023-04-21
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Mundipharma Research Ltd.
External identifiers
- EU CT number
- 2022-501985-23-00
- ClinicalTrials.gov
- NCT05534529
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Safety
To evaluate the pharmacokinetics (PK) of a single IV dose of rezafungin in paediatric subjects from birth to <18 years, receiving concomitant systemic antifungals as prophylaxis for invasive fungal infection (IFI) or to treat a suspected or confirmed fungal infection
Secondary objectives 1
- To assess the safety and tolerability of a single IV dose of rezafungin in paediatric subjects from birth to <18 years, receiving concomitant systemic antifungals as prophylaxis for IFI or to treat a suspected or confirmed fungal infection
Conditions and MedDRA coding
Fungal infections
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10017534 | Fungal infection NOS | 10021881 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Part 1 Part 1 will include subjects aged 12 to <18 years (Group 1).
Subjects in Group 1 (12 to <18 years) will be dosed first. PK sampling will be performed at the following 5 timepoints following administration of rezafungin.
An interim review of safety and PK data will be conducted by the Data Safety Monitoring Board (DSMB) after completion of Group 1 to ensure that exposure achieved in the subjects from this group is safe and well tolerated. This will allow for a decision to proceed to Part 2
|
Not Applicable | None | Group 1: Group 1 (12 to <18 years): 8 subjects | |
| 2 | Part 2 Part 2 will include subjects aged 6 to <12 years (Group 2), and subjects aged 2 to <6 years (Group 3).
Enrolment for Group 2 and Group 3 will commence in parallel after safety has been confirmed by the DSMB. The PK sampling will be performed at the same 5 timepoints as that in Part 1 following administration of rezafungin
A second interim review of safety and PK data will be performed when data from 50% of the subjects enrolled in Part 2 (Group 2 and Group 3) are available. The dose and PK sampling timepoints may be adjusted as appropriate after review of the PK and safety data (DSMB review 2). After completion of Groups 2 and 3; there will be another interim review (DSMB review 3) of the safety, tolerability, and PK data from the subjects in Groups 1, 2, and 3 (all subjects in Part 1 and Part 2).
|
Not Applicable | None | Group 2: Group 2 (6 to <12 years): 8 subjects Group 3: Group 3 (2 to <6 years): 8 subjects |
|
| 3 | Part 3 Part 3 will include subjects from birth to <2 years of age (Group 4).
Subjects from birth to <2 years of age (Group 4) will be enrolled after safety has been confirmed by the third DSMB review. PK sampling will be done at 3 timepoints following administration of rezafungin. The dose, PK sampling timepoints, extent of safety laboratory data required, and length of the Follow-up period may be adjusted as appropriate after review of the PK and safety data from Part 1 and Part 2 (DSMB review 3).
|
Not Applicable | None | Group 4: Group 4 (birth to <2 years): 8 subjects |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- EMA paediatric investigation plan (PIP)
- EMEA-002319-PIP01-17
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Male or female paediatric subjects from birth to <18 years of age who are receiving concomitant systemic antifungals (oral or IV) as prophylaxis for IFI or to treat a suspected or confirmed fungal infection.
Exclusion criteria 6
- History of anaphylaxis, hypersensitivity, or any serious reaction to the echinocandin class of antifungals and/or excipients of this formulation;
- Previous or current medical conditions of severe ataxia, persistent tremors, intracranial haemorrhage or neuropathy, or a diagnosis of epilepsy, multiple sclerosis, or a movement disorder (including, but not limited to, cerebral palsy and muscular dystrophy);
- Subjects with impaired renal or hepatic functions (alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal, conjugated bilirubin >24 µmol/L [1.4 mg/dL], serum creatinine >177 µmol/L [2 mg/dL], or receiving renal replacement therapy);
- Subjects with intestinal hypoxia, ischaemia, necrosis, or necrotising enterocolitis;
- Subject status is unstable (e.g., with sepsis or disseminated intravascular coagulation), and subject is unlikely to complete required study procedures;
- Participation in another interventional treatment trial with an investigational agent or presence of an investigational device at the time of informed consent or within 28 days preceding the informed consent.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Parts 1 and 2: The following PK parameters will be assessed: Cmax, Tmax, AUC0-t, AUC0-∞, CL, Vss, Vz, t1/2
- Part 3: Rezafungin plasma concentrations
Secondary endpoints 1
- The safety evaluation will be based on clinical review of the following parameters: • Incidence of treatment-emergent adverse events (TEAEs) • Clinical laboratory evaluations (including haematology, blood chemistry and urinalysis) • Vital signs • 12-lead electrocardiograms (ECGs): clinically significant abnormalities • Physical examination findings
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
REZZAYO 200 mg powder for concentrate for solution for infusion
PRD9931889 · Product
- Active substance
- Rezafungin Acetate
- Pharmaceutical form
- POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Authorisation status
- Not Authorised
- MA holder
- MUNDIPHARMA RESEARCH LTD
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2385
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Mundipharma Research Limited
- Sponsor organisation
- Mundipharma Research Limited
- Address
- 196 Science Park, Milton Road Milton Road
- City
- Cambridge
- Postcode
- CB4 0AB
- Country
- United Kingdom
Scientific contact point
- Organisation
- Mundipharma Research Limited
- Contact name
- Gu-Lung Lin
Public contact point
- Organisation
- Mundipharma Research Limited
- Contact name
- Terry Nichols
Third parties 5
| Organisation | City, country | Duties |
|---|---|---|
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Almac Clinical Services Limited ORG-100011829
|
Craigavon, United Kingdom | Code 14, Other |
| Icon Laboratories Inc. ORG-100037135
|
Farmingdale, United States | Other |
| Stichting Radboud University Medical Center ORG-100023234
|
Nijmegen, Netherlands | Other, Laboratory analysis |
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | On site monitoring, Code 10, Code 11, Code 13, Code 14, Other, Code 2, Code 5, Data management, Code 8 |
Mundipharma Research Limited
- Sponsor organisation
- Mundipharma Research Limited
- Address
- 196 Science Park, Milton Road Milton Road
- City
- Cambridge
- Postcode
- CB4 0AB
- Country
- United Kingdom
Scientific contact point
- Organisation
- Mundipharma Research Limited
- Contact name
- Gu-Lung Lin
Public contact point
- Organisation
- Mundipharma Research Limited
- Contact name
- Terry Nichols
Third parties 5
| Organisation | City, country | Duties |
|---|---|---|
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Almac Clinical Services Limited ORG-100011829
|
Craigavon, United Kingdom | Code 14, Other |
| Icon Laboratories Inc. ORG-100037135
|
Farmingdale, United States | Other |
| Stichting Radboud University Medical Center ORG-100023234
|
Nijmegen, Netherlands | Other, Laboratory analysis |
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | On site monitoring, Code 10, Code 11, Code 13, Code 14, Other, Code 2, Code 5, Data management, Code 8 |
Locations
2 EU/EEA countries · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ended | 12 | 3 |
| Spain | Ended | 12 | 3 |
| Rest of world
United Kingdom
|
— | 16 | — |
Investigational sites
Goethe University Frankfurt
Clinic for Pediatric and Adolescent Medicine, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
Universitaetsklinikum Essen AöR
Department for Pediatrics III, Hufelandstrasse 55, Holsterhausen, Essen
Westfaelische Wilhelms Universitaet Muenster
Department of Pediatric Hematology/ Oncology, Gebäude A1, Albert-Schweitzer-Campus 1, Münster
Hospital Universitario 12 De Octubre
Pediatric Infectious Diseases, Bloque D, Avenida De Cordoba S/n, Madrid
Area De Salud De Burgos Y Soria
Pediatric Hematology, Avenida De Las Islas Baleares 3, 09006, Burgos
Hospital Universitario La Paz
Pediatric Hemato-Oncology, Paseo Castellana 261, 28046, Madrid
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 |
|---|---|---|---|---|---|
| Germany | 2023-06-19 | 2023-09-08 | 2024-05-04 | ||
| Spain | 2023-05-18 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 2 · Art. 38 CTR
Temporary halt TH-24211
- Halt date
- 2024-05-04
- Member states concerned
- Spain
- Publication date
- 2024-05-07
- Reason
- Sponsor decision
- Explanation
- Mundipharma Research Ltd. will put the study on temporary recruitment hold after 03-May-2024 due to the impending expiration of the current batch of investigational product. Participants enrolled on or prior to 03-May-2024 will continue with the study until the follow-up visit. There have been significant challenges to enrolment and as a result, Mundipharma plans to propose a new study strategy to the Paediatric Committee (PDCO) of the EMA whilst this study is on hold. Our commitment to rezafungin development in the paediatric population remains unchanged. We consistently review our strategies and adapt our study designs to meet patient needs and facilitate enrolment. Once a decision has been agreed with PDCO on the future strategy of the study, the study will either be restarted with a substantial amendment including a new IMPD related to a new batch of investigational product, or an early termination of the study will be submitted.
- Benefit-risk balance changed
- No
- Treatment stopped
- Yes
Temporary halt TH-24212
- Halt date
- 2024-05-04
- Member states concerned
- Germany
- Publication date
- 2024-05-07
- Reason
- Sponsor decision
- Explanation
- Mundipharma Research Ltd. will put the study on temporary recruitment hold after 03-May-2024 due to the impending expiration of the current batch of investigational product. Participants enrolled on or prior to 03-May-2024 will continue with the study until the follow-up visit. There have been significant challenges to enrolment and as a result, Mundipharma plans to propose a new study strategy to the Paediatric Committee (PDCO) of the EMA whilst this study is on hold. Our commitment to rezafungin development in the paediatric population remains unchanged. We consistently review our strategies and adapt our study designs to meet patient needs and facilitate enrolment. Once a decision has been agreed with PDCO on the future strategy of the study, the study will either be restarted with a substantial amendment including a new IMPD related to a new batch of investigational product, or an early termination of the study will be submitted.
- Benefit-risk balance changed
- No
- 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 |
|---|---|---|---|
| Study results SUM-78445
|
2025-04-09T13:04:37 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Trial results | 2025-04-09T13:04:47 | Submitted | Laypersons Summary of Results |
Documents 4 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Layperson Summary of Results | 1 |
| Laypersons summary of results (for publication) | Layperson Summary of Results_German | 1 |
| Laypersons summary of results (for publication) | Layperson Summary of Results_Spanish | 1 |
| Summary of results (for publication) | Summary of Results | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-11-28 | Spain | Acceptable 2023-04-17
|
2023-04-18 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-04-26 | Acceptable | 2023-05-03 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-08-01 | Spain | Acceptable 2023-10-30
|
2023-10-31 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2023-11-09 | Spain | Acceptable 2023-10-30
|
2023-11-09 |