Clinical Trial Results:
An open-label, non-randomized, single center, single dose, exploratory phase II trial of FG001 (an imaging agent) for localization of oral and oropharyngeal squamous cell carcinoma
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Summary
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EudraCT number |
2022-001361-12 |
Trial protocol |
DK |
Global end of trial date |
11 Jul 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Mar 2024
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First version publication date |
29 Mar 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
FG001-CT-003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
FluoGuide A/S
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Sponsor organisation address |
Ole Maaløes Vej 3, Copenhagen, Denmark, DK-2200
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Public contact |
Andreas Kjær, MD, PhD, DMSc
Chief Medical Officer, FluoGuide A/S, +45 3131 0844,
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Scientific contact |
Andreas Kjær, MD, PhD, DMSc
Chief Medical Officer, FluoGuide A/S, +45 3131 0844,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Oct 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Jul 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Jul 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
• To evaluate FG001 for the detection of oral and oropharyngeal cancer
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Protection of trial subjects |
The trial was conducted, in compliance with the protocol, regulatory requirements, Good Clinical Practice (GCP) and the ethical principles of the latest revision of the Declaration of Helsinki as adopted
by the World Medical Association.
All subjects provided written informed consent to participate in the trial prior to being screened. All subjects received written and verbal information regarding the trial. The given information emphasized that participation in the trial was voluntary and that the subjects could withdraw from the trial at any time and for any reason. All subjects were given the opportunity to ask questions about the trial and were given sufficient time to decide whether to participate in the trial.
A subject was discontinued from the trial at any time if the subject, the Investigator, or the FluoGuide A/S evaluated that it was not in the subject´s best interest to continue. The following were possible
reasons for trial treatment discontinuation:
• Subject withdrawal of consent.
• Subject was not compliant with trial procedures.
• AE that in the opinion of the Investigator was in the best interest of the subject to discontinue trial participation.
• Protocol violation requiring discontinuation.
• Lost to follow-up.
• FluoGuide A/S request for early termination of trial.
• Subject death.
All subjects could withdraw from participation at any time, for any reason, specified or unspecified, and without prejudice. Reasonable attempts were made by the Investigator to provide a reason for the subject’s withdrawal. The reason for the subject’s withdrawal from the trial was specified in the subject’s journal and the eCRF. If a subject was withdrawn from treatment due to an AE, the subject was followed and treated by the Investigator until the abnormal parameter or symptom has resolved or stabilized.
Although subjects could withdraw from the trial at any time and for any reason, subject withdrawal was avoided to the extent possible.
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Background therapy |
None. | ||
Evidence for comparator |
None. | ||
Actual start date of recruitment |
18 Nov 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 17
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Worldwide total number of subjects |
17
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EEA total number of subjects |
17
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
11
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85 years and over |
1
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Recruitment
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Recruitment details |
This study was conducted at Copenhagen University Hospital, Rigshospitalet, Denmark. A total of 20 subjects were screened and 17 subjects were finally enrolled in the trial: four were included in the FG001 36 mg group, eight in the FG001 16 mg group and five in the FG001 4 mg group. One subject was withdrawn due to being inoperative. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
At the screening visit the subject´s medical history and concomitant illnesses were obtained, and the previous and concomitant medication documented. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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FG001 36 mg | ||||||||||||||||||||
Arm description |
Four subjects received FG001 at a dose of 36 mg. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
FG001
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
The FG001 DP i.v. consisted of a vial containing 5.2 mg freeze-dried FG001 for reconstitution with sterile water for injection (sWfI) prior to use. All subjects received a single dose, slowly i.v. injection (up to 10 minutes) of the IMP (batch numbers: B4002507 and B4003582).
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Arm title
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FG001 16 mg | ||||||||||||||||||||
Arm description |
Eight subjects received FG001 at a dose of 16 mg. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
FG001
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
The FG001 DP i.v. consisted of a vial containing 5.2 mg freeze-dried FG001 for reconstitution with sterile water for injection (sWfI) prior to use. All subjects received a single dose, slowly i.v. injection (up to 10 minutes) of the IMP (batch numbers: B4002507 and B4003582).
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Arm title
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FG001 4 mg | ||||||||||||||||||||
Arm description |
Five subjects received FG001 at a dose of 4 mg. One subject discontinued the trial by physician’s decision since the subject had no valid TBR imaging information. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
FG001
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
The FG001 DP i.v. consisted of a vial containing 5.2 mg freeze-dried FG001 for reconstitution with sterile water for injection (sWfI) prior to use. All subjects received a single dose, slowly i.v. injection (up to 10 minutes) of the IMP (batch numbers: B4002507 and B4003582).
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Baseline characteristics reporting groups
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Reporting group title |
FG001 36 mg
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Reporting group description |
Four subjects received FG001 at a dose of 36 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FG001 16 mg
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Reporting group description |
Eight subjects received FG001 at a dose of 16 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FG001 4 mg
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Reporting group description |
Five subjects received FG001 at a dose of 4 mg. One subject discontinued the trial by physician’s decision since the subject had no valid TBR imaging information. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
FG001 36 mg
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Reporting group description |
Four subjects received FG001 at a dose of 36 mg. | ||
Reporting group title |
FG001 16 mg
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Reporting group description |
Eight subjects received FG001 at a dose of 16 mg. | ||
Reporting group title |
FG001 4 mg
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Reporting group description |
Five subjects received FG001 at a dose of 4 mg. One subject discontinued the trial by physician’s decision since the subject had no valid TBR imaging information. | ||
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End point title |
Sensitivity for Detection of Oral and Oropharyngeal Cancer Verified by Histology [1] | ||||||||||||||||
End point description |
The sensitivity was evaluated as the proportion of subjects with fluorescent tumors given the tumor had been histologically verified.
The efficacy of FG001 (as a tumor imaging agent) was examined by the sensitivity, which was verified via the intensity of fluorescence from the specimen sampled. As per standard procedure at site the
histopathological evaluation of a section of the tumor was performed.
A positive result was defined as correspondence between presence of cancer tissue in the biopsy sampled in an area with optical signal within the macroscopically visible tumor.
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End point type |
Primary
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End point timeframe |
During surgery, punch biopsies were sampled to confirm sensitivity histopathologically.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Not applicable. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Tumor To Background Ratio (TBR): Signal intensity in tumor | ||||||||||||||||||||||||||||||||||||
End point description |
The optimal image for each subject was annotated for the tumor and three representative backgrounds (suspected healthy tissue). On the selected image, the tumor was annotated (delineated) based on the surgeon´s knowledge of where the tumor was placed (including depth of tumor, as applicable). Hereafter, the areas of the anticipated healthy tissue were annotated as backgrounds. These were annotated as large areas near the tumor but anticipated not to be part of the tumor, both in vivo and ex vivo, for all subjects. An annotation tool was used for this and generated a pixel-based intensity value (range from 0-255). From the intensity values, a TBR was calculated.
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End point type |
Secondary
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End point timeframe |
TBR was a secondary efficacy endpoint and was calculated as the fluorescence of the tumor relative to background tissue, as measured by NIR imaging. This was imaged in situ during resection.
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
PK profile determined by non-compartmental analysis | ||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Samples were used to evaluate the PKs of FG001 and were taken at the following timepoints from administration of FG001: +1 Hour (± 15 minutes), +13 hours (±2 hours), +24 hours (± 4 hours), +36 hours (± 4 hours), and +44 hours (± 6 hours).
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| Notes [2] - N Cmax=4 N tmax=4 N AUC0-inf=4 N AUC0-last=4 N t1/2=4 [3] - N Cmax=8 N tmax=8 N AUC0-inf=7 N AUC0-last=8 N t1/2=7 [4] - N Cmax=5 N tmax=5 N AUC0-inf=0 N AUC0-last=3 N t1/2=0 |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Safety was closely followed during the course of the trial.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
FG001 36 mg
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Reporting group description |
Four subjects received FG001 at a dose of 36 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FG001 16 mg
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Reporting group description |
Eight subjects received FG001 at a dose of 16 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FG001 4 mg
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Reporting group description |
Five subjects received FG001 at a dose of 4 mg. One subject discontinued the trial by physician’s decision since the subject had no valid TBR imaging information. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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23 Mar 2023 |
This change was made to update the Interim Evaluation (IE).
Description of changes:
• Inclusion of a dosing visit the day before surgery.
• Inclusion of the safety data as part of the IE meeting.
• Update of the IE.
• Inclusion of a new exclusion criterion (INR<1.7).
• Correction of minor inconsistencies. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
