Pulmonary Aspergillosis - InvasivePhase 1/2SAFEGUARDNCT02856178
Study on Safety and Pharmacokinetics of Intravenous F901318 for Fungal Prophylaxis in AML Patients
A Phase 1/2 study testing F901318 and Caspofungin in people with Pulmonary Aspergillosis - Invasive and Acute Myeloid Leukemia, run by F2G Ltd.
Trial summary
This study assesses the pharmacokinetics and safety of the new antifungal F901318 in AML patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Aspergillosis - Invasive, Acute Myeloid Leukemia
- What is being tested?
- F901318 and Caspofungin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 20 Apr 2017to 20 Apr 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with AML and entering treatment of chemotherapy.
- Patients are expected to be neutropenic (< 500 ANC/μl) for > 10 days.
- Provision of written informed consent prior to any study specific procedures.
- Ability and willingness to comply with the protocol.
- Patients aged over 18 years.
- Patient has or will receive within 2 days a multi-lumen central venous catheter as standard of care.
Who cannot join
- Documented lung infiltrate at screening.
- Documented serum GMI ≥0.5 at screening
- Current IFD or prior history of IFD or patients who received systemic antifungal therapy for proven or probable IFD in the last 12 months.
- Patients who received any systemic antifungal therapy for more than 72 hours immediately prior to first administration of study medication. Echinocandins and topical polyenes or nystatin are acceptable. Posaconazole and other azoles have to be discontinued at least 3 days before start of F901318.
- Concomitant exposure to phenobarbital and long acting barbiturates, triazolam, carbamazepine, phenytoin, pimozide, cisapride, efavirenz, ritonavir, rifabutin, rifampicin, ergot alkaloids (ergotamine, dihydroergotamin), ibrutinib, idelalisib, vinca alkaloids, digoxin, dofetilide, quinidine, St. John´s wort, everolimus, sirolimus, astemizole, terfenadine, methadone, alfentanil, fentanyl and other structurally related opiates, warfarin.
- Documented prolongation of the QTc interval (>450 ms).
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- Concomitant medication that prolongs QT interval (except for cytostatic drugs used during chemotherapy, such as mitoxantrone).
- Any other concomitant medical condition that, in the opinion of the investigator, may be an unacceptable additional risk to the patient should he/she participate in the study.
- History of convulsion.
- Female patients only: Positive result of pregnancy test or breastfeeding.
- Female patients of childbearing potential who do not agree to not have sexual intercourse during the study or who do not use or do not agree to use appropriate contraceptive methods (prior to and during the study, including 14 days after the last dose of study therapy) as defined in ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals (EMA/CPMP/ICH/286/1995). Hormonal contraception alone is not considered appropriate.
- Known hypersensitivity to any component of the study medication.
- A history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalaemia, cardiomyopathy, sinus bradycardia, symptomatic arrhythmias, family history of long QT Syndrome).
- Patient has had acute hepatitis in the prior 6 months, chronic hepatitis, cirrhosis (any Child-Pugh class), acute hepatic failure, or acute decompensation of chronic hepatic failure
- Presence of hepatic disease as indicated by aspartate aminotransferase (AST) or alanine transaminase (ALT)>3 × upper limit of normal (ULN) at Screening. Patients with AST and/or ALT >3 × ULN and <5 × ULN are eligible if these elevations are acute, not accompanied by a total bilirubin ≥2xULN and documented by the investigator as being directly related to an infectious process being treated. During the clinical study, the investigator is responsible for, without delay, determining whether the patient meets potential Hy's law criteria (according to FDA [28]).
- Patient has a total bilirubin >3 × ULN, unless isolated hyperbilirubinemia is directly related to an acute infection or due to known Gilbert's disease.
- Calculated creatinine clearance (CrCl) < 50 mL/minute.
- Medical history of oliguria (< 20 mL/h) unresponsive to fluid challenge.
- Suspected other or additional cause for neutropenia or immunosuppression (other than AML or myelodysplastic syndrome).
- Any other medical condition which may affect the clinical evaluability of the patient.
- Patients previously enrolled in this study.
- Patient has participated or intends to participate in any other clinical study that involves the administration of an investigational medication at the time of presentation, during the course of the study, or during the 30 days prior to study start. New combinations of labelled substances for chemotherapy are allowed.
- Chronic ocular disease.
- Contact lens use intended during study treatment.
About this study
Official title: An Open Label Phase IIa Clinical Study to Evaluate the Safety and Pharmacokinetics of Intravenous and Oral F901318 (Combined With Caspofungin) for Antifungal Prophylaxis in Patients Undergoing Chemotherapy for Acute Myeloid Leukaemia
This study assesses the pharmacokinetics and safety of the new antifungal F901318 in AML patients.
Read the detailed description
F901318 has potent in vitro efficacy against Aspergillus spp. including azole-resistant strains and consistent efficacy in in vivo mouse models of infection. F901318 is active by both oral and intravenous routes of administration in preclinical efficacy studies.
Non-clinical studies and phase I clinical trials show that F901318 has a good overall safety profile and limited potential for drug-drug interactions. F901318 exhibits a highly promising profile which can potentially address the critical treatment requirements for invasive Aspergillus infections in a changing clinical environment in which new classes of antifungals are needed.
This phase IIa study aims to confirm PK and safety information of F901318 from phase I and bridge them to a neutropenic AML patient population, which represents the main population for future efficacy trials. Coadministration of caspofungin will allow recognizing potential factors of suboptimal F901318 exposure without the risk of fatal disseminating infection.
- Being tested
- F901318, Caspofungin
- Medical subject headings
- Invasive Pulmonary Aspergillosis, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
F901318Drug
F901318 treatment starting after completion of chemotherapy. Max. 14 days of intravenous F901318 b.i.d. treatment, followed by one oral dose of F901318. Loading doses 4 mg/kg b.i.d. , maintenance doses 2 mg/kg b.i.d.
CaspofunginDrug
Also called Cancidas®
Intravenous Caspofungin treatment starting during chemotherapy for concomitant prophylaxis of fungal infection. Loading dose 70 mg q.d., maintenance doses 50 mg q.d.
| Study group | Role | What they receive |
|---|---|---|
| F901318 + Caspofungin | Experimental | Patients will receive F901318 intravenously, starting 24 - 72 h after last chemotherapy infusion:
* Day 1: 4.0 mg/kg i.v. b.i.d.
* Day 2 until resolution of neutropenia (max. until day 14): 2.0 mg/kg i.v. b.i.d.
* Day after last i.v. application: 2.0 mg/kg oral q.d.
Concomitant medication:
For Candida prophylaxis, concomitant caspofungin will be administered from the 4th day of chemotherapy until end of neutropenia:
* Chemo day 4: Caspofungin 70 mg i.v. q.d.
* Chemo day 5 until resolution of neutropenia or until end of F901318 treatment (day 15): Caspofungin 50 mg i.v. q.d.
All patients will undergo chemotherapy for acute leukaemia according to local clinical standard. Receives: Drug: F901318; Drug: Caspofungin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Collection of adverse events, results of physical examination, vital signs, ECGs, and laboratory assessments during F901318 intravenous infusion and oral formulation.
Measured: 57 days
Secondary outcomes (14)
Concentration-time profile of F901318 following i.v. administration
F901318 trough level assessment for 14 days once per day. On three of these 14 days additional samples for determination of plasma concentration of F901318 will be collected.
Measured: 14 days
Measured concentration of F901318 at the end of an i.v. dosing interval at steady state (Ctrough)
Measured: 14 days
Minimum observed plasma or serum, concentration of F901318 during an i.v. dosing interval at steady state (Cmin, ss)
Measured: 14 days
Maximum observed plasma or serum, concentration of F901318 during an i.v. dosing interval at steady state (Cmax, ss)
Measured: 14 days
Average plasma or serum concentration of F901318 at steady state after i.v. administration (Cav,ss)
Measured: 14 days
Area under the concentration-time curve during a F901318 i.v. dosing interval at steady state calculated by trapezoidal rule (AUCT,ss)
Measured: 14 days
Area under the concentration vs. time curve from point zero up to the end of infusion of F901318 (AUC(0-T))
T: total time of infusion
Measured: 14 days
Area under the concentration vs. time curve from time point zero up to the time point t (AUC(0-t)) for F901318 after i.v. administration
Measured: 14 days
Area under the concentration vs. time curve from time point zero up to the last measured concentration of F901318 above LOQ (AUC(0-t_last)) after i.v. administration
Measured: 14 days
Apparent terminal half-life (t1/2) of F901318 after i.v. administration
Measured: 14 days
Terminal rate constant (λz) of F901318 after i.v. administration
Measured: 14 days
Apparent clearance (Cl) of F901318 after i.v. administration
Measured: 14 days
Plasma concentration of F901318 after oral application
Measurement 2h, 4h, 12h and 24h after oral intake of F901318
Measured: 1 day
Number of patients developing an possible/probable/proven invasive fungal disease (IFD) according to EORTC/MSG criteria
Patients galactomannan index and body temperature will be assessed regularly. If it is clinically indicated the patients will undergo a CT, which will be checked for infiltrations. If infiltrations are detected the patients will undergo a bronchoalveolar lavage, the result of which will be used to analyse BAL GMI, to grow a microbiological culture, to perform histology and perform an Aspergillus PCR. On the basis of the available data for each patient the scientific advisory committee will assess the number of patients suffering from a possible/probable or proven IFD.
Measured: 57 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2016 (estimated)
- Study start20 Apr 2017
- Primary completion20 Apr 2017
- Study completion20 Apr 2017
Why it stopped: study no longer required
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Aspergillosis - InvasiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- F2G Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University Hospital of Cologne
- Responsible party
- Sponsor
- Investigators
- Oliver Cornely, PhD, MD, Principal investigator, University Hospital of Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02856178
- Sponsor's protocol ID
- F901318C20
- Acronym
- SAFEGUARD
- Status last verified
- Aug 2016
- First submitted
- 14 Jul 2016
- Last updated
- 15 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase IIa Clinical Study to Evaluate the Safety and Pharmacokinetics of Intravenous and Oral F901318 (Combined With Caspofungin) for Antifungal Prophylaxis in Patients Undergoing Chemotherapy for Acute Myeloid Leukaemia
- ClinicalTrials.gov ID
- NCT02856178
- Acronym / sponsor ID
- SAFEGUARD / F901318C20
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: study no longer required
- Enrolment
- 0 participants (actual)
- Lead sponsor
- F2G LtdIndustry (pharma, biotech, devices)
- Collaborators
- University Hospital of Cologne
- Study start
- 20 Apr 2017 (actual)
- Primary completion
- 20 Apr 2017 (actual)
- Study completion
- 20 Apr 2017 (actual)
- First posted
- 4 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study assesses the pharmacokinetics and safety of the new antifungal F901318 in AML patients.
Detailed description
F901318 has potent in vitro efficacy against Aspergillus spp. including azole-resistant strains and consistent efficacy in in vivo mouse models of infection. F901318 is active by both oral and intravenous routes of administration in preclinical efficacy studies.
Non-clinical studies and phase I clinical trials show that F901318 has a good overall safety profile and limited potential for drug-drug interactions. F901318 exhibits a highly promising profile which can potentially address the critical treatment requirements for invasive Aspergillus infections in a changing clinical environment in which new classes of antifungals are needed.
This phase IIa study aims to confirm PK and safety information of F901318 from phase I and bridge them to a neutropenic AML patient population, which represents the main population for future efficacy trials. Coadministration of caspofungin will allow recognizing potential factors of suboptimal F901318 exposure without the risk of fatal disseminating infection.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| F901318 + Caspofungin | Experimental | Drug: F901318, Drug: CaspofunginPatients will receive F901318 intravenously, starting 24 - 72 h after last chemotherapy infusion: * Day 1: 4.0 mg/kg i.v. b.i.d. * Day 2 until resolution of neutropenia (max. until day 14): 2.0 mg/kg i.v. b.i.d. * Day after last i.v. application: 2.0 mg/kg oral q.d. Concomitant medication: For Candida prophylaxis, concomitant caspofungin will be administered from the 4th day of chemotherapy until end of neutropenia: * Chemo day 4: Caspofungin 70 mg i.v. q.d. * Chemo day 5 until resolution of neutropenia or until end of F901318 treatment (day 15): Caspofungin 50 mg i.v. q.d. All patients will undergo chemotherapy for acute leukaemia according to local clinical standard. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients diagnosed with AML and entering treatment of chemotherapy.
- Patients are expected to be neutropenic (< 500 ANC/μl) for > 10 days.
- Provision of written informed consent prior to any study specific procedures.
- Ability and willingness to comply with the protocol.
- Patients aged over 18 years.
Key exclusion criteria (24 listed)
- Documented lung infiltrate at screening.
- Documented serum GMI ≥0.5 at screening
- Current IFD or prior history of IFD or patients who received systemic antifungal therapy for proven or probable IFD in the last 12 months.
- Patients who received any systemic antifungal therapy for more than 72 hours immediately prior to first administration of study medication. Echinocandins and topical polyenes or nystatin are acceptable. Posaconazole and other azoles have to be discontinued at least 3 days before start of F901318.
- Concomitant exposure to phenobarbital and long acting barbiturates, triazolam, carbamazepine, phenytoin, pimozide, cisapride, efavirenz, ritonavir, rifabutin, rifampicin, ergot alkaloids (ergotamine, dihydroergotamin), ibrutinib, idelalisib, vinca alkaloids, digoxin, dofetilide, quinidine, St. John´s wort, everolimus, sirolimus, astemizole, terfenadine, methadone, alfentanil, fentanyl and other structurally related opiates, warfarin.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| F901318F901318 treatment starting after completion of chemotherapy. Max. 14 days of intravenous F901318 b.i.d. treatment, followed by one oral dose of F901318. Loading doses 4 mg/kg b.i.d. , maintenance doses 2 mg/kg b.i.d. | Drug | F901318 + Caspofungin |
| CaspofunginAlso: Cancidas®Intravenous Caspofungin treatment starting during chemotherapy for concomitant prophylaxis of fungal infection. Loading dose 70 mg q.d., maintenance doses 50 mg q.d. | Drug | F901318 + Caspofungin |
Primary outcome
Collection of adverse events, results of physical examination, vital signs, ECGs, and laboratory assessments during F901318 intravenous infusion and oral formulation.
Time frame: 57 days
14 secondary outcomes
Concentration-time profile of F901318 following i.v. administration
Time frame: 14 days
Measured concentration of F901318 at the end of an i.v. dosing interval at steady state (Ctrough)
Time frame: 14 days
Minimum observed plasma or serum, concentration of F901318 during an i.v. dosing interval at steady state (Cmin, ss)
Time frame: 14 days
Maximum observed plasma or serum, concentration of F901318 during an i.v. dosing interval at steady state (Cmax, ss)
Time frame: 14 days
Average plasma or serum concentration of F901318 at steady state after i.v. administration (Cav,ss)
Time frame: 14 days
Area under the concentration-time curve during a F901318 i.v. dosing interval at steady state calculated by trapezoidal rule (AUCT,ss)
Time frame: 14 days
Area under the concentration vs. time curve from point zero up to the end of infusion of F901318 (AUC(0-T))
Time frame: 14 days
Area under the concentration vs. time curve from time point zero up to the time point t (AUC(0-t)) for F901318 after i.v. administration
Time frame: 14 days
Area under the concentration vs. time curve from time point zero up to the last measured concentration of F901318 above LOQ (AUC(0-t_last)) after i.v. administration
Time frame: 14 days
Apparent terminal half-life (t1/2) of F901318 after i.v. administration
Time frame: 14 days
Terminal rate constant (λz) of F901318 after i.v. administration
Time frame: 14 days
Apparent clearance (Cl) of F901318 after i.v. administration
Time frame: 14 days
Plasma concentration of F901318 after oral application
Time frame: 1 day
Number of patients developing an possible/probable/proven invasive fungal disease (IFD) according to EORTC/MSG criteria
Time frame: 57 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oliver Cornely, PhD, MD principal investigator
University Hospital of Cologne
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing F901318 and Caspofungin in people with Pulmonary Aspergillosis - Invasive and Acute Myeloid Leukemia, run by F2G Ltd.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Collection of adverse events, results of physical examination, vital signs, ECGs, and laboratory assessments during F901318 intravenous infusion and oral formulation. (time frame: 57 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2018.