Clinical Trial Results:
Proof of Concept study concerning efficacy of P03277 MR Imaging in HCC diagnosis
Phase IIa Clinical Study
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Summary
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EudraCT number |
2016-002930-62 |
Trial protocol |
FR |
Global end of trial date |
04 Apr 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Oct 2020
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First version publication date |
28 Oct 2020
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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 |
GDX-44-008
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02973516 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GUERBET
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Sponsor organisation address |
BP 57400, Roissy CdG, France, 95943, Villepinte, France, 93420
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Public contact |
Jing HAO, Global Head of Medical Affairs & Clinical Development, GUERBET, 33 0145917626, jing.hao@guerbet.com
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Scientific contact |
Jing HAO, Global Head of Medical Affairs & Clinical Development, GUERBET, 33 0145915176, jing.hao@guerbet.com
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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 |
04 Apr 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Apr 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Apr 2019
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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 the diagnostic value for hepatocellular carcinoma (HCC) of P03277 in patients with suspected small nodules and chronic liver disease.
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Protection of trial subjects |
This trial has been conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, that are consistent with Good Clinical Practice (GCP) according to International Conference on Harmonisation (ICH) guidelines and with the applicable regional/local regulations of the country in which the trial was conducted.
The safety data were monitored during the whole study period.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Dec 2016
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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 |
France: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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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) |
24
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From 65 to 84 years |
16
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||
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Pre-assignment
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Screening details |
- | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
40 | |||||||||
Number of subjects completed |
40 | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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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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P03277 - 0.1 mmol/kg | |||||||||
Arm description |
Subjects who have received P03277 (gadopiclenol) at the dose of 0.1 mmol/kg | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
P03277
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Investigational medicinal product code |
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Other name |
gadopiclenol
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
0.1 mmol/kg in a single injection
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Arm title
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P03277 - 0.05 mmol/kg | |||||||||
Arm description |
Subjects who have received P03277 (gadopiclenol) at the dose of 0.05 mmol/kg | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
P03277
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Investigational medicinal product code |
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Other name |
gadopiclenol
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
0.05 mmol/kg in a single injection
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial (overall period)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
P03277 - 0.1 mmol/kg
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Reporting group description |
Subjects who have received P03277 (gadopiclenol) at the dose of 0.1 mmol/kg | ||
Reporting group title |
P03277 - 0.05 mmol/kg
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Reporting group description |
Subjects who have received P03277 (gadopiclenol) at the dose of 0.05 mmol/kg | ||
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End point title |
HCC diagnosis according to gadopiclenol MR imaging [1] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
1 day procedure
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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: As a proof of concept study, no statistical analyses were performed. |
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End point title |
HCC diagnosis according to standard of reference [2] | |||||||||||||||
End point description |
The standard of reference is composed of histology analysis or two previous contrast-enhanced imaging (CT and/or MRI) and/or the most recent AFP results available.
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End point type |
Primary
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End point timeframe |
Data collected before inclusion or at the optional visit 4 (up to 13 weeks after contrast administration)
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| Notes [2] - 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: As a proof of concept study, no statistical analyses were performed. |
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End point title |
Diagnostic value evaluation for HCC [3] | |||||||||||||||||||||||||||
End point description |
Sensitivity: number of nodules showing true positive HCC divided by all nodules considered HCC according to standard of reference.
Specificity: number of nodules showing true negative HCC divided by all nodules considered as not HCC or uncertain according to standard of reference.
Accuracy: number of nodules showing true positive HCC and true negative HCC over all nodules.
Positive predictive value: number of nodules showing true positive HCC divided by all nodules showing HCC according to gadopiclenol MR imaging.
Negative predictive value: number of nodules showing true negative HCC divided by all nodules not showing HCC according to gadopiclenol MR imaging.
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End point type |
Primary
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End point timeframe |
Based on data collected before inclusion or at the optional visit 4 (up to 13 weeks after contrast administration) for the standard of reference and day 1 for gadopiclenol MR imaging.
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| Notes [3] - 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: As a proof of concept study, no statistical analyses were performed. |
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Adverse events information
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Timeframe for reporting adverse events |
From informed consent signature to 1 day after contrast injection and at optional visit 4 (up to 13 weeks after contrast injection)
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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 |
20.1
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Reporting groups
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Reporting group title |
P03277 all doses
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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01 Dec 2016 |
- Corrections within inclusion and non-inclusion criteria about duration of amenorrhea (>12 months amenorrhea) for post-menopausal criteria and accepted contraception methods.
- Only one pregnancy test was required within 24h before gadopiclenol administration.
- Only random glucose was required instead of glucose under fasting conditions.
- Efficacy evaluation was reviewed and made consistent.
- Race and ethnicity were needed to be collected.
- The safety reporting section was modified according to new pharmacovigilance requirements in France and within Europe and for better management of new signal detection. |
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12 Dec 2017 |
- An additional 3D GRE T1 sequence with fat saturation was added at 15 ± 5 minutes in order to better see the kinetics of gadopiclenol.
- A second cohort of 10 additional patients were recruited and received a dose of 0.05 mmol/kg.
- It was acceptable to consider for standard of reference results of histology done within 2 months prior to gadopiclenol MR imaging.
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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. | |||
| Gadopiclenol at 0.05 mmol/kg seems sufficient for HCC diagnosis. Gadopiclenol at 0.1 mmol/kg prolonged wash-out time at portal/delayed phases due to its high relaxivity, leading to lower diagnostic accuracy as per EASL guidelines diagnostic criteria | |||
