Prostatic Neoplasms, Prostate Cancer, Recurrence
Conditions
Keywords
[18F]CTT1057, [68Ga]Ga-PSMA-11, Positron Emission Tomography/Computerized Tomography, PET/CT, Radioligand, Imaging, Biochemical recurrence, BCR, Composite Truth Standard, CTS, Prostate Cancer, PCa
Brief summary
The current study aimed at evaluating the diagnostic performance of \[18F\]CTT1057 as a PET imaging agent for detection and localization of Prostate specific membrane antigen (PSMA) positivity in patients diagnosed of biochemical recurrence of prostate cancer (PCa), using a composite truth standard. Approximately 190 participants were to be enrolled to ensure at least 152 participants were evaluable (i.e. have both an evaluable \[18F\]CTT1057 Positron emission tomography/Computed Tomography (PET/CT) scan imaging and at least one evaluable Composite Truth Standard (CTS) assessment and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CTs and CTS procedures, which were required for the calculation of the co-primary endpoints.
Detailed description
This was a prospective, open-label, multi center, single-arm Phase III study to evaluate the diagnostic performance of \[18F\]CTT1057 as a PET imaging agent for detection and localization of PSMA positive tumors in PCa patients diagnosed with biochemical recurrence (BCR) after initial definitive therapy with either radical prostatectomy (RP) or curative intent radiation therapy (RT), using a CTS as reference. The CTS to be used as reference were hierarchical in nature, with 3 levels of Standard of Truth (SoT) procedures, that were applied as follows: CTS Level 1: Histopathology if available for the lesion (from prospective biopsy or salvage surgery performed within 8 weeks after the \[18F\]CTT1057 PET/CT scan); OR in case that histopathology was not available for a lesion, inconclusive or negative (for biopsy only). CTS Level 2: Imaging diagnostic procedures performed on each patient as clinically indicated per SoC, which included at least a high resolution CT scan with contrast and a \[68Ga\]Ga-PSMA-11 PET/CT) performed within 8 weeks (either before or after) the \[18F\]CTT1057 PET/CT scan. Three-month follow-up imaging (from baseline) were also be used as part of the CTS level 2 in cases where it is clinically required for the diagnosis of particular lesion(s); OR if neither of the two above were feasible or deemed appropriate or they were inconclusive. CTS Level 3: 50% or greater decline in PSA following radiation therapy (as long as no concomitant androgen deprivation therapy (ADT) was given) as per Prostate Cancer Working Group 3 (PCWG3) criteria. All participants underwent 2 PET/CT scans: one with the investigational agent \[18F\]CTT1057 and another with \[68Ga\]Ga-PSMA-11 (as a component of the CTS Level 2 and for a secondary endpoint of assessment of concordance between the 2 PET/CT scans for detection of lesions). The 2 PET imaging procedures were performed at least 14 days apart, and the PET/CT scan sequence for each participant was assigned at random in a 1:1 ratio.
Interventions
DRUG[18F]CTT1057
Single intravenous dose of approximately 370 Mega-Becquerel (MBq) and subsequent PET/CT scan
DRUG[68Ga]Ga-PSMA-11
Single intravenous dose of approximately 150 MBq and subsequent PET/CT scan
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Once eligibility was confirmed, the participants were randomized in IRT to be assigned to one of the following two PET/CT scan sequences at random in a 1:1 ratio: * Sequence 1: \[18F\]CTT1057 on Day 1 (investigational imaging agent of interest) followed by \[68Ga\]Ga-PSMA-11 at least 14 days apart (as part of CTS if required, and for secondary endpoint) * Sequence 2: \[68Ga\]Ga-PSMA-11 (as part of CTS if required, and for secondary endpoint) on Day 1 followed by \[18F\]CTT1057 (investigational imaging agent of interest) at least 14 days apart
Eligibility
Sex/Gender
MALE
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent must be obtained prior to participation in the study * Biopsy proven prostate adenocarcinoma. * Biochemical recurrence following initial definitive therapy (with either RP or curative intent radiation therapy) as defined: by AUA criteria (Cookson et al 2007) for patients who have undergone RP: Initial serum PSA of ≥0.2 ng/ml measured at least 6 weeks after RP with a second confirmatory persistent PSA level of \>0.2 ng/ml, or by ASTRO-Phoenix criteria (Roach et al 2006) for patients who have undergone curative-intent radiation therapy (RT): Rise of serum PSA measurement of 2 or more ng/mL above the nadir PSA observed post RT. * ECOG performance status 0-2 * Participants must be adults ≥ 18 years of age
Exclusion criteria
* Inability to complete the needed investigational and standard-of-care imaging examinations due to any reason (severe claustrophobia, inability to lie still for the entire imaging time, etc.) * Any additional medical condition, serious intercurrent illness, concomitant cancer or other extenuating circumstance that, in the opinion of the Investigator, would indicate a significant risk to safety or impair study participation, including, but not limited to, current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, need of indwelling/condom catheters, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, and COVID-19 * Prior major surgery undergone less than 12 weeks prior to screening (with the exception of any surgery related to prostatic cancer) * Known allergy, hypersensitivity, or intolerance to \[18F\]CTT1057, \[68Ga\]Ga-PSMA-11, or to CT contrast * Prior and current use of PSMA targeted therapies * Prior ADT (first or second generation), including LHRH analogues (agonists or antagonists), within 9 months before screening * Any 5-alpha reductase inhibitors within 30 days before screening * Use of other investigational drugs within 30 days before screening * Castration-resistant patients * Patient with small cell or neuroendocrine PCa in more than 50% of biopsy tissue * Prior salvage surgery or salvage radiation therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Region-level correct localization rate (CLR) is defined as the percentage of regions containing at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings within the same region, out of all regions containing at least one PET-positive finding. |
| Patient-level Positive Predictive Value (PPV) (With Anatomical Localization) of Vidoflufolastat (18F) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Patient-level positive predictive value (PPV) is defined as the percentage of participants who have at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all participants who are PET/CT scan positive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient-level Negative Predictive Value (NPV) of Vidoflufolastat (18F) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Patient-level negative predictive value is defined as the percentage of participants who are both vidoflufolastat (18F) and CTS negative (True Negative (TN)) among those who test negative on vidoflufolastat (18F) (True Negative (TN) or False Negative (FN)). |
| Patient-level Accuracy of Vidoflufolastat (18F) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Patient-level accuracy is defined as the percentage of participants who are CTS and vidoflufolastat (18F) positive (True Positive (TP)) and negative (True Negative (TN)) among those participants that identified on vidoflufolastat (18F) (True Positive (TP), True Negative (TN), False Positive (FP) or False Negative (FN)). |
| Patient-level Correct Detection Rate (CDR) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Patient-level correct detection rate (CDR) is defined as the percentage of participants who have at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all participants who are scanned. |
| Patient-level Detection Rate | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Patient-level detection rate is defined as the percentage of participants who have at least one PET positive lesion, regardless of True Positive (TP) or False Positive (FP) findings, out of all participants who are scanned. |
| Region Level Specificity of Vidoflufolastat (18F) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Region level specificity is defined as the percentage of regions that test negative on both vidoflufolastat (18F) and CTS (True Negative (TN)) among those regions that are CTS negative (False Positive (FP) or True Negative (TN)). |
| Region-level Sensitivity of Vidoflufolastat (18F) (Overall) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Region level sensitivity is defined as the percentage of regions that test positive on both vidoflufolastat (18F) and CTS (True Positive (TP)) among those regions that are CTS positive (True Positive (TP) or False Negative (FN)). |
| Region Level Negative Predictive Value (NPV) of Vidoflufolastat (18F) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Region level negative predictive value is defined as the percentage of regions that are CTS and vidoflufolastat (18F) negative (True Negative (TN)) among those regions that test negative on vidoflufolastat (18F) (True Negative (TN) or False Negative (FN)). |
| Patient-level Sensitivity of Vidoflufolastat (18F) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Patient-level sensitivity is defined as the percentage of participants who test positive on vidoflufolastat (18F) and Composite Truth Standard (CTS) (True Positive (TP)) among those that are CTS positive (True Positive (TP) or False Negative (FN)). |
| Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Patient-level positive predictive value related to PSA levels is defined as the percentage of participants who have at least one True Positive (TP) lesion (exactly anatomically localized correspondence between vidoflufolastat (18F) PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all participants who are vidoflufolastat (18F) positive, stratified by PSA levels. This endpoint was analyzed in each of the following subgroups: PSA ≤ 0.5 ng/mL; 0.5 ng/mL\<PSA≤1 ng/mL; 1 ng/mL\<PSA≤2 ng/mL; 2 ng/mL\<PSA≤5 ng/mL; PSA \> 5 ng/mL. |
| Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | From first dosing (Day 1) up to 14 days post dosing | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. |
| Vidoflufolastat (18F) Scan Inter-reader Variability | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Inter-reader variability is defined as the agreement among three readers determination of vidoflufolastat (18F) images. |
| Vidoflufolastat (18F) Scan Intra-reader Variability | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Intra-reader variability is defined as the within-reader agreement for two different time points of vidoflufolastat (18F) images. |
| Concordance Between Vidoflufolastat (18F) and Gallium (68Ga) Gozetotide for Detection of Lesions at Lesion Level Using Central Reads (Overall) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Concordance between vidoflufolastat (18F) and gallium (68Ga) gozetotide for detection of PSMA-positive lesions (location and number) using central reads. |
| Change in Patient Management Plans Attributed to the Vidoflufolastat (18F) PET/CT Scan | From randomization up to 14 days after obtaining the results of the vidoflufolastat (18F) PET imaging | Change in patient management plans attributed to the PET/CT scan is defined as the percentage of participants who underwent a change in intended treatment plan attributed to the vidoflufolastat (18F) PET/CT scan as assessed by pre and post imaging questionnaires. |
| Region Level Accuracy of Vidoflufolastat (18F) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Region level accuracy is defined as the percentage of regions that are CTS andvidoflufolastat (18F) positive (True Positive (TP)) and negative (True Negative (TN)) among those regions that identified on vidoflufolastat (18F) (True Positive (TP), True Negative (TN), False Positive (FP) and False Negative (FN)). |
| Patient-level Specificity of Vidoflufolastat (18F) | vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment) | Patient-level specificity is defined as the percentage of participants who test negative on vidoflufolastat (18F) and CTS (True Negative (TN)) among those that are CTS negative (True Negative (TN) or False Positive (FP)). |
Countries
France, Spain, Switzerland, United States
Participant flow
Recruitment details
190 participants were randomized using a 1:1 ratio to receive either Sequence 1 (vidoflufolastat (18F) followed by gallium (68Ga) gozetotide; N= 96) or Sequence 2 (gallium (68Ga) gozetotide followed by vidoflufolastat (18F); N=94). Out of the 190 randomized participants, 169 completed the study.
Pre-assignment details
Prior to participation in the study, patients had to have biopsy proven prostate adenocarcinoma and diagnosis of biochemical recurrence following initial definitive therapy with either radical prostatectomy or curative intent radiation therapy.
Participants by arm
| Arm | Count |
|---|---|
| PET/CT Imaging With Vidoflufolastat (18F) Followed by Gallium (68Ga) Gozetotide or Vice Versa All eligible participants were assigned to one of the following two PET/CT scan sequences at random in a 1:1 ratio:- Sequence 1: vidoflufolastat (18F) on Day 1 (investigational imaging agent of interest) followed by gallium (68Ga) gozetotide at least 14 days apart (as part of CTS if required, and for secondary endpoint)- Sequence 2: gallium (68Ga) gozetotide (as part of CTS if required, and for secondary endpoint) on Day 1 followed by vidoflufolastat (18F) (investigational imaging agent of interest) at least 14 days apart | 190 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Deviation | 3 | 2 |
| Overall Study | Technical Problems | 0 | 5 |
| Overall Study | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | PET/CT Imaging With Vidoflufolastat (18F) Followed by Gallium (68Ga) Gozetotide or Vice Versa |
|---|---|
| Age, Continuous | 67.2 Years STANDARD_DEVIATION 7.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 63 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 108 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 19 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized Unknown | 4 Participants |
| Race/Ethnicity, Customized White | 180 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 190 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 171 | 0 / 178 |
| other Total, other adverse events | 20 / 171 | 16 / 178 |
| serious Total, serious adverse events | 1 / 171 | 0 / 178 |
Outcome results
Primary
Patient-level Positive Predictive Value (PPV) (With Anatomical Localization) of Vidoflufolastat (18F)
Patient-level positive predictive value (PPV) is defined as the percentage of participants who have at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all participants who are PET/CT scan positive.
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all randomized participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan imaging and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CTs and CTS procedures. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Positive Predictive Value (PPV) (With Anatomical Localization) of Vidoflufolastat (18F) | 76.5 Percentage of participants |
| Central Reader 2 | Patient-level Positive Predictive Value (PPV) (With Anatomical Localization) of Vidoflufolastat (18F) | 69.0 Percentage of participants |
| Central Reader 3 | Patient-level Positive Predictive Value (PPV) (With Anatomical Localization) of Vidoflufolastat (18F) | 64.6 Percentage of participants |
Primary
Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F)
Region-level correct localization rate (CLR) is defined as the percentage of regions containing at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings within the same region, out of all regions containing at least one PET-positive finding.
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all randomized participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan imaging and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CTs and CTS procedures. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F) | 75.0 Percentage of regions |
| Central Reader 2 | Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F) | 68.9 Percentage of regions |
| Central Reader 3 | Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F) | 65.2 Percentage of regions |
Secondary
Change in Patient Management Plans Attributed to the Vidoflufolastat (18F) PET/CT Scan
Change in patient management plans attributed to the PET/CT scan is defined as the percentage of participants who underwent a change in intended treatment plan attributed to the vidoflufolastat (18F) PET/CT scan as assessed by pre and post imaging questionnaires.
Time frame: From randomization up to 14 days after obtaining the results of the vidoflufolastat (18F) PET imaging
Population: The vidoflufolastat (18F) Safety Set (F-SAF) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Central Reader 1 | Change in Patient Management Plans Attributed to the Vidoflufolastat (18F) PET/CT Scan | 61 Participants |
Secondary
Concordance Between Vidoflufolastat (18F) and Gallium (68Ga) Gozetotide for Detection of Lesions at Lesion Level Using Central Reads (Overall)
Concordance between vidoflufolastat (18F) and gallium (68Ga) gozetotide for detection of PSMA-positive lesions (location and number) using central reads.
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The vidoflufolastat (18F) Safety Set (F-SAF) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Concordance Between Vidoflufolastat (18F) and Gallium (68Ga) Gozetotide for Detection of Lesions at Lesion Level Using Central Reads (Overall) | 51.1 Percentage of lesions |
| Central Reader 2 | Concordance Between Vidoflufolastat (18F) and Gallium (68Ga) Gozetotide for Detection of Lesions at Lesion Level Using Central Reads (Overall) | 48.2 Percentage of lesions |
| Central Reader 3 | Concordance Between Vidoflufolastat (18F) and Gallium (68Ga) Gozetotide for Detection of Lesions at Lesion Level Using Central Reads (Overall) | 55.1 Percentage of lesions |
Secondary
Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject.
Time frame: From first dosing (Day 1) up to 14 days post dosing
Population: Safety set (SAF): All participants who received at least one dose of vidoflufolastat (18F) or Gallium (68Ga) gozetotide.~The vidoflufolastat (18F) Safety Set (F-SAF) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)).~The gallium (68Ga) gozetotide safety Set (Ga-SAF) included all participants who received Gallium (68Ga) gozetotide.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Adverse Events (AEs) | 20 Participants |
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Treatment-related AEs | 6 Participants |
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Serious Adverse Events (SAEs) | 1 Participants |
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Fatal serious AEs | 0 Participants |
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Treatment-related fatal AEs | 0 Participants |
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | AEs leading to treatment discontinuation | 0 Participants |
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Treatment-related AEs leading to treatment discontinuation | 0 Participants |
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | AEs leading to dose adjustment / interruption | 0 Participants |
| Central Reader 1 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | AEs requiring additional therapy | 2 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Treatment-related AEs leading to treatment discontinuation | 0 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Adverse Events (AEs) | 16 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Treatment-related fatal AEs | 0 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Treatment-related AEs | 2 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | AEs requiring additional therapy | 4 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Serious Adverse Events (SAEs) | 0 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | AEs leading to treatment discontinuation | 0 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | AEs leading to dose adjustment / interruption | 0 Participants |
| Central Reader 2 | Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) | Fatal serious AEs | 0 Participants |
Secondary
Patient-level Accuracy of Vidoflufolastat (18F)
Patient-level accuracy is defined as the percentage of participants who are CTS and vidoflufolastat (18F) positive (True Positive (TP)) and negative (True Negative (TN)) among those participants that identified on vidoflufolastat (18F) (True Positive (TP), True Negative (TN), False Positive (FP) or False Negative (FN)).
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Accuracy of Vidoflufolastat (18F) | 78.9 Percentage of participants |
| Central Reader 2 | Patient-level Accuracy of Vidoflufolastat (18F) | 76.4 Percentage of participants |
| Central Reader 3 | Patient-level Accuracy of Vidoflufolastat (18F) | 75.2 Percentage of participants |
Secondary
Patient-level Correct Detection Rate (CDR)
Patient-level correct detection rate (CDR) is defined as the percentage of participants who have at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all participants who are scanned.
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Correct Detection Rate (CDR) | 24.2 Percenage of participants |
| Central Reader 2 | Patient-level Correct Detection Rate (CDR) | 24.8 Percenage of participants |
| Central Reader 3 | Patient-level Correct Detection Rate (CDR) | 26.1 Percenage of participants |
Secondary
Patient-level Detection Rate
Patient-level detection rate is defined as the percentage of participants who have at least one PET positive lesion, regardless of True Positive (TP) or False Positive (FP) findings, out of all participants who are scanned.
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Detection Rate | 31.7 Percentage of participants |
| Central Reader 2 | Patient-level Detection Rate | 36.0 Percentage of participants |
| Central Reader 3 | Patient-level Detection Rate | 40.4 Percentage of participants |
Secondary
Patient-level Negative Predictive Value (NPV) of Vidoflufolastat (18F)
Patient-level negative predictive value is defined as the percentage of participants who are both vidoflufolastat (18F) and CTS negative (True Negative (TN)) among those who test negative on vidoflufolastat (18F) (True Negative (TN) or False Negative (FN)).
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Negative Predictive Value (NPV) of Vidoflufolastat (18F) | 80.0 Percentage of participants |
| Central Reader 2 | Patient-level Negative Predictive Value (NPV) of Vidoflufolastat (18F) | 80.6 Percentage of participants |
| Central Reader 3 | Patient-level Negative Predictive Value (NPV) of Vidoflufolastat (18F) | 82.3 Percentage of participants |
Secondary
Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels
Patient-level positive predictive value related to PSA levels is defined as the percentage of participants who have at least one True Positive (TP) lesion (exactly anatomically localized correspondence between vidoflufolastat (18F) PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all participants who are vidoflufolastat (18F) positive, stratified by PSA levels. This endpoint was analyzed in each of the following subgroups: PSA ≤ 0.5 ng/mL; 0.5 ng/mL\<PSA≤1 ng/mL; 1 ng/mL\<PSA≤2 ng/mL; 2 ng/mL\<PSA≤5 ng/mL; PSA \> 5 ng/mL.
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Central Reader 1 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: 2 ng/mL <PSA <= 5 ng/mL (n=11,11,11) | 100 Percentage of Participants |
| Central Reader 1 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: 1 ng/mL <PSA <= 2 ng/mL (n = 11, 11, 11) | 75.0 Percentage of Participants |
| Central Reader 1 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: PSA <= 0.5 ng/mL (n = 100,100,100) | 60.9 Percentage of Participants |
| Central Reader 1 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: 0.5 ng/mL <PSA <= 1 ng/mL (n = 29, 29, 29) | 100 Percentage of Participants |
| Central Reader 1 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: PSA > 5 ng/mL (n = 6,6,6) | 100 Percentage of Participants |
| Central Reader 2 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: 1 ng/mL <PSA <= 2 ng/mL (n = 11, 11, 11) | 71.4 Percentage of Participants |
| Central Reader 2 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: PSA <= 0.5 ng/mL (n = 100,100,100) | 59.3 Percentage of Participants |
| Central Reader 2 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: 0.5 ng/mL <PSA <= 1 ng/mL (n = 29, 29, 29) | 66.7 Percentage of Participants |
| Central Reader 2 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: 2 ng/mL <PSA <= 5 ng/mL (n=11,11,11) | 100 Percentage of Participants |
| Central Reader 2 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: PSA > 5 ng/mL (n = 6,6,6) | 100 Percentage of Participants |
| Central Reader 3 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: PSA > 5 ng/mL (n = 6,6,6) | 100 Percentage of Participants |
| Central Reader 3 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: 2 ng/mL <PSA <= 5 ng/mL (n=11,11,11) | 66.7 Percentage of Participants |
| Central Reader 3 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: PSA <= 0.5 ng/mL (n = 100,100,100) | 53.3 Percentage of Participants |
| Central Reader 3 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: 1 ng/mL <PSA <= 2 ng/mL (n = 11, 11, 11) | 71.4 Percentage of Participants |
| Central Reader 3 | Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels | Subgroup: 0.5 ng/mL <PSA <= 1 ng/mL (n = 29, 29, 29) | 76.9 Percentage of Participants |
Secondary
Patient-level Sensitivity of Vidoflufolastat (18F)
Patient-level sensitivity is defined as the percentage of participants who test positive on vidoflufolastat (18F) and Composite Truth Standard (CTS) (True Positive (TP)) among those that are CTS positive (True Positive (TP) or False Negative (FN)).
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all randomized participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan imaging and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CTs and CTS procedures. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Sensitivity of Vidoflufolastat (18F) | 63.9 Percentage of participants |
| Central Reader 2 | Patient-level Sensitivity of Vidoflufolastat (18F) | 66.7 Percentage of participants |
| Central Reader 3 | Patient-level Sensitivity of Vidoflufolastat (18F) | 71.2 Percentage of participants |
Secondary
Patient-level Specificity of Vidoflufolastat (18F)
Patient-level specificity is defined as the percentage of participants who test negative on vidoflufolastat (18F) and CTS (True Negative (TN)) among those that are CTS negative (True Negative (TN) or False Positive (FP)).
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Specificity of Vidoflufolastat (18F) | 88.0 Percentage of participants |
| Central Reader 2 | Patient-level Specificity of Vidoflufolastat (18F) | 82.2 Percentage of participants |
| Central Reader 3 | Patient-level Specificity of Vidoflufolastat (18F) | 77.5 Percentage of participants |
Secondary
Region Level Accuracy of Vidoflufolastat (18F)
Region level accuracy is defined as the percentage of regions that are CTS andvidoflufolastat (18F) positive (True Positive (TP)) and negative (True Negative (TN)) among those regions that identified on vidoflufolastat (18F) (True Positive (TP), True Negative (TN), False Positive (FP) and False Negative (FN)).
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region Level Accuracy of Vidoflufolastat (18F) | 93.7 Percentage of regions |
| Central Reader 2 | Region Level Accuracy of Vidoflufolastat (18F) | 93.3 Percentage of regions |
| Central Reader 3 | Region Level Accuracy of Vidoflufolastat (18F) | 92.7 Percentage of regions |
Secondary
Region Level Negative Predictive Value (NPV) of Vidoflufolastat (18F)
Region level negative predictive value is defined as the percentage of regions that are CTS and vidoflufolastat (18F) negative (True Negative (TN)) among those regions that test negative on vidoflufolastat (18F) (True Negative (TN) or False Negative (FN)).
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region Level Negative Predictive Value (NPV) of Vidoflufolastat (18F) | 95.1 Percentage of regions |
| Central Reader 2 | Region Level Negative Predictive Value (NPV) of Vidoflufolastat (18F) | 95.5 Percentage of regions |
| Central Reader 3 | Region Level Negative Predictive Value (NPV) of Vidoflufolastat (18F) | 95.4 Percentage of regions |
Secondary
Region-level Sensitivity of Vidoflufolastat (18F) (Overall)
Region level sensitivity is defined as the percentage of regions that test positive on both vidoflufolastat (18F) and CTS (True Positive (TP)) among those regions that are CTS positive (True Positive (TP) or False Negative (FN)).
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region-level Sensitivity of Vidoflufolastat (18F) (Overall) | 53.2 Percentage of regions |
| Central Reader 2 | Region-level Sensitivity of Vidoflufolastat (18F) (Overall) | 58.2 Percentage of regions |
| Central Reader 3 | Region-level Sensitivity of Vidoflufolastat (18F) (Overall) | 58.0 Percentage of regions |
Secondary
Region Level Specificity of Vidoflufolastat (18F)
Region level specificity is defined as the percentage of regions that test negative on both vidoflufolastat (18F) and CTS (True Negative (TN)) among those regions that are CTS negative (False Positive (FP) or True Negative (TN)).
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region Level Specificity of Vidoflufolastat (18F) | 98.1 Percentage of regions |
| Central Reader 2 | Region Level Specificity of Vidoflufolastat (18F) | 97.1 Percentage of regions |
| Central Reader 3 | Region Level Specificity of Vidoflufolastat (18F) | 96.5 Percentage of regions |
Secondary
Vidoflufolastat (18F) Scan Inter-reader Variability
Inter-reader variability is defined as the agreement among three readers determination of vidoflufolastat (18F) images.
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The vidoflufolastat (18F) Safety Set (F-SAF) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Vidoflufolastat (18F) Scan Inter-reader Variability | 65.5 % agreement |
Secondary
Vidoflufolastat (18F) Scan Intra-reader Variability
Intra-reader variability is defined as the within-reader agreement for two different time points of vidoflufolastat (18F) images.
Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Population: The vidoflufolastat (18F) Safety Set (F-SAF) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)). Scans for a subset of 19 participants from the vidoflufolastat (18F) safety set were read by each reader at 2 different time points
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Vidoflufolastat (18F) Scan Intra-reader Variability | 61.2 % agreement |
| Central Reader 2 | Vidoflufolastat (18F) Scan Intra-reader Variability | 100 % agreement |
| Central Reader 3 | Vidoflufolastat (18F) Scan Intra-reader Variability | 100 % agreement |