Amyloidosis
Conditions
Keywords
Amyloid light chain (AL), Amyloid Transthyretin Systemic Amyloidosis (ATTR)
Brief summary
This study is designed to assess the repeatability of organ-specific quantitation of radiotracer uptake following Positron Emission Tomography/Computed Tomography (PET/CT) imaging of AT- 01 in subjects with amyloid light chain (AL) or amyloid transthyretin (ATTR) systemic amyloidosis.
Detailed description
This is a multicenter, open label, single arm study in subjects with amyloid light chain (AL) or amyloid transthyretin (ATTR) systemic amyloidosis with visceral amyloid deposits. This study consists of a screening period of up to 30 days; two one-day treatment periods (Day 1 and Week 6); a safety follow-up 24-48 hours after the second administration of 124I AT-01, and a safety follow-up visit 28 days after the second administration of 124I-AT-01.
Interventions
DRUG124I-AT-01
All participants received 1 mCi 124I-AT-01 on Day 1 and at Week 6 via IV infusion over 2-5 minutes or slow IV bolus at 1 mL/5 seconds.
Sponsors
Attralus, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Single arm, no placebo, no comparator
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Understands the study procedures and is capable of giving signed informed consent, as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. Male or female ≥18 years of age. 3. For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 90 days after the last dose of 124I-AT-01. 1. A woman is considered of childbearing potential if she is postmenarchal, has not reached a postmenopausal state, and has not undergone surgical sterilization. 2. Examples of contraceptive methods with a failure rate of \<1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. 3. Contraception methods that do not result in a failure rate of \<1% per year such as cap, diaphragm, or sponge with spermicide, or male or female condom with or without spermicide, are not acceptable. 4. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. 4. For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm, as defined below: a) With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year during the treatment period and for at least 120 days (a spermatogenesis cycle) after the last dose of study intervention. Men must refrain from donating sperm during this same time period. 5. Able to undergo two PET/CT scans as part of the study, including ability to lie supine for up to 1 hour. 6. Has a history of AL or ATTR systemic amyloidosis with at least one organ with clinically demonstrable amyloid involvement defined by: 1. AL systemic amyloidosis: Positive tissue biopsy for AL amyloid, and achieved a hematologic very good partial response or complete response based on their most recent assessment, and at least one of the following: 1) Organ biopsy positive for amyloid, or 2) Natriuretic peptide (NT-proBNP) \>650 pg/mL, or 3) left ventricle septal wall thickness \>12 mm by echocardiogram or cardiac magnetic resonance (CMR), or 4) 24-hour urine protein \>500 mg, or 5) Urine albumin-to-creatinine ratio \>300 mg/g 2. ATTR (wild type or variant) systemic amyloidosis: Positive cardiac biopsy for ATTR amyloid, or at least two of the following: 1) Positive extracardiac tissue biopsy for ATTR amyloid or positive transthyretin gene mutation associated with amyloid, or 2) left ventricle septal wall thickness \>12 mm by echocardiogram or CMR, or 3) pyrophosphate (PYP) scintigraphy with myocardial uptake ≥grade 2.
Exclusion criteria
1. Is pregnant or breast-feeding. 2. Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of psychosis. 3. Has received in the last 6 months or are currently receiving treatment with anti-amyloid monoclonal antibody therapy or are expected to begin treatment prior to completing this study. 4. Has received heparin or heparin analogs within 7 days of Day 1. 5. Has a significant co-morbidity (e.g., Easter Cooperative Oncology Group (ECOG) score of 3 or greater), New York Heart Association (NYHA) Class IV heart failure, uncontrolled infection, or other ongoing serious illness. 6. Has active thyroid disease. 7. Has a known allergy to potassium iodine treatment. 8. Is receiving hemodialysis or peritoneal dialysis. 9. Has severe claustrophobia that would prevent completion of the PET/CT imaging protocol. 10. Has received an investigational agent within five half-lives of the agent or 30 days, whichever is longer, prior to Screening. 11. Has any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Day 1 and Week 6 | Between-visit repeatability of organ-specific (heart, kidney, liver, spleen) quantitation (SUVmax) of radiotracer uptake following PET/CT imaging of 124I-AT-01 in participants with AL or ATTR systemic amyloidosis was assessed. wCV with its associated 95% RC provides guidance on the level of change in organ-specific quantitation of radiotracer uptake that needs to be observed to be confident that a true change in uptake has occurred. Smaller values of wCV represent better agreement. Computation of wCV and associated RCs in addition to the two-sided 95% CI is described in the SAP. Only images from participants/organs with positive uptake were included. RCs between visits were calculated using the difference of the log of the average of the 2 reads for a reader at Day 1 and the log of the average of the 2 reads for the same reader at Week 6. The 95% RCs were calculated on the log-transformed data and exponentiated to determine the limits in percentages. |
| Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Day 1 and Week 6 | Between-visit repeatability of organ-specific (heart, kidney, liver, spleen) quantification (SUVpeak) of radiotracer uptake following PET/CT imaging of 124I-AT-01 in participants with AL or ATTR systemic amyloidosis was assessed. wCV with its associated 95% RC provides guidance on the level of change in organ-specific quantitation of radiotracer uptake that needs to be observed to be confident that a true change in uptake has occurred. Computation of wCV and associated RCs in addition to the two-sided 95% CI is described in the SAP. Only images from participants/organs with positive uptake were included. RCs between visits were calculated using the difference of the log of the average of the 2 reads for a reader at Day 1 and the log of the average of the 2 reads for the same reader at Week 6. The 95% RCs were calculated on the log-transformed data and exponentiated to determine the limits in percentages. |
| Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Day 1 and Week 6 | Repeatability of organ-specific (heart, kidney, liver, spleen) quantification (SUVmax) of radiotracer uptake following PET/CT imaging of 124I-AT-01 in participants with AL or ATTR systemic amyloidosis was assessed. ICC assesses the consistency or reproducibility of measurements made by the 3 readers measuring the same participant images. Reader results are the average of the reader's 2 reads for the specific visit. A two-way mixed effects model with absolute agreement type for a single rater/measurement was used to calculate the ICC. The ICC coefficient is the ratio of the between-cluster variance to the total variance (denoted as r in the SAP). Fisher's z-transformation was used to calculate the 95% confidence intervals. A two-sided 95% CI is computed based upon the formulary provided in the SAP. |
| Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Day 1 and Week 6 | Repeatability of organ-specific (heart, kidney, liver, spleen) quantification (SUVpeak) of radiotracer uptake following PET/CT imaging of 124I-AT-01 in participants with AL or ATTR systemic amyloidosis was assessed. ICC assesses the consistency or reproducibility of measurements made by the 3 readers measuring the same participant images. Reader results are the average of the reader's 2 reads for the specific visit. A two-way mixed effects model with absolute agreement type for a single rater/measurement was used to calculate the ICC. The ICC coefficient is the ratio of the between-cluster variance to the total variance (denoted as r in the SAP). Fisher's z-transformation was used to calculate the 95% confidence intervals. A two-sided 95% CI is computed based upon the formulary provided in the SAP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Laboratory Values - Chemistry (IU/L) | At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6) | Changes from baseline in chemistry clinical laboratory values with units of IU/L |
| Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6) | Changes from baseline in hematology clinical laboratory values with units of % of WBC count |
| Clinical Laboratory Values - Hematology (10^9 Cells/L) | At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6) | Changes from baseline in hematology clinical laboratory values with units of 10\^9 cells/L |
| Clinical Laboratory Values - Hematology (10^12 Cells/L) | At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6) | Changes from baseline in hematology clinical laboratory values with units of 10\^12 cells/L |
| Number of Participants With At Least 1 Treatment-Emergent Adverse Event (TEAE) | Day 1 through the end of the study (up to 14 weeks) | TEAEs were defined as events that were newly reported or reported to worsen in severity after the start of treatment. Adverse events (AEs) that occurred after the treatment start date, occurred on the treatment start date with a time that was equal to or after treatment start time, or that had a missing AE start date were categorized as treatment emergent. |
| Clinical Laboratory Values - Hematology (% of Total Blood Cell Count) | At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6) | Changes from Baseline in hematology clinical laboratory values with units of % of total blood cell count |
| Change From Baseline in Vital Signs - Blood Pressure (mmHg) | Day 1 post-administration and Week 6 pre-administration and post-administration | Changes from baseline in blood pressure measurements with units of mmHg |
| Change From Baseline in Vital Signs - Heart Rate (Beats/Min) | Day 1 post-administration and Week 6 pre-administration and post-administration | Changes from baseline in heart rate measurements with units of beats/min |
| Change From Baseline in Anti-Drug Antibodies (ADA) | Post-dose at Week 6 or Safety Follow-up 2 (28 days after Week 6) | Changes from baseline in ADA |
| Clinical Laboratory Values - Hematology (g/L) | At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6) | Change from baseline in hematology clinical laboratory values with units of g/L |
| Clinical Laboratory Values - Chemistry (mmol/L) | At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6) | Changes from baseline in chemistry clinical laboratory values with units of mmol/L |
| Clinical Laboratory Values - Chemistry (Umol/L) | At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6) | Changes from baseline in chemistry clinical laboratory values with units of umol/L |
| Clinical Laboratory Values - Chemistry (g/L) | At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6) | Changes from baseline in chemistry clinical laboratory values with units of g/L |
Countries
United States
Participant flow
Pre-assignment details
Of the initial 34 participants screened, 32 participants met inclusion criteria and were enrolled for treatment. Two participants were screen failures, one of whom was re-screened and subsequently enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| 124I-AT-01 All participants received 1 mCi 124I-AT-01 on Day 1 and at Week 6 via IV infusion over 2-5 minutes or slow IV bolus at 1 mL/5 seconds. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Participant elected to drop out (i.e., not undergo second scan) but did not withdraw consent | 1 |
| Overall Study | Protocol-specified withdrawal criterion met | 5 |
Baseline characteristics
| Characteristic | 124I-AT-01 |
|---|---|
| Age, Continuous | 65.1 years STANDARD_DEVIATION 10.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment United States | 33 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 33 |
| other Total, other adverse events | 13 / 33 |
| serious Total, serious adverse events | 1 / 33 |
Outcome results
Primary
Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake
Repeatability of organ-specific (heart, kidney, liver, spleen) quantification (SUVmax) of radiotracer uptake following PET/CT imaging of 124I-AT-01 in participants with AL or ATTR systemic amyloidosis was assessed. ICC assesses the consistency or reproducibility of measurements made by the 3 readers measuring the same participant images. Reader results are the average of the reader's 2 reads for the specific visit. A two-way mixed effects model with absolute agreement type for a single rater/measurement was used to calculate the ICC. The ICC coefficient is the ratio of the between-cluster variance to the total variance (denoted as r in the SAP). Fisher's z-transformation was used to calculate the 95% confidence intervals. A two-sided 95% CI is computed based upon the formulary provided in the SAP.
Time frame: Day 1 and Week 6
Population: The Image Evaluable Set was defined as all participants who underwent PET/CT scans on both Day 1 and 6 to 8 weeks after Day 1 and who had evaluable images at both time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Day 1 | 0.903 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Week 6 | 0.955 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Day 1 | 0.973 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Week 6 | 0.964 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Day 1 | 0.971 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Week 6 | 0.975 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Day 1 | 0.991 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Week 6 | 0.996 correlation coefficient |
Primary
Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake
Repeatability of organ-specific (heart, kidney, liver, spleen) quantification (SUVpeak) of radiotracer uptake following PET/CT imaging of 124I-AT-01 in participants with AL or ATTR systemic amyloidosis was assessed. ICC assesses the consistency or reproducibility of measurements made by the 3 readers measuring the same participant images. Reader results are the average of the reader's 2 reads for the specific visit. A two-way mixed effects model with absolute agreement type for a single rater/measurement was used to calculate the ICC. The ICC coefficient is the ratio of the between-cluster variance to the total variance (denoted as r in the SAP). Fisher's z-transformation was used to calculate the 95% confidence intervals. A two-sided 95% CI is computed based upon the formulary provided in the SAP.
Time frame: Day 1 and Week 6
Population: The Image Evaluable Set was defined as all participants who underwent PET/CT scans on both Day 1 and 6 to 8 weeks after Day 1 and who had evaluable images at both time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Day 1 | 0.960 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Week 6 | 0.987 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Day 1 | 0.994 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Week 6 | 0.991 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Day 1 | 0.993 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Week 6 | 0.990 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Day 1 | 0.997 correlation coefficient |
| 124I-AT-01 | Intraclass Correlation Coefficient (ICC) Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Week 6 | 0.999 correlation coefficient |
Primary
Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake
Between-visit repeatability of organ-specific (heart, kidney, liver, spleen) quantitation (SUVmax) of radiotracer uptake following PET/CT imaging of 124I-AT-01 in participants with AL or ATTR systemic amyloidosis was assessed. wCV with its associated 95% RC provides guidance on the level of change in organ-specific quantitation of radiotracer uptake that needs to be observed to be confident that a true change in uptake has occurred. Smaller values of wCV represent better agreement. Computation of wCV and associated RCs in addition to the two-sided 95% CI is described in the SAP. Only images from participants/organs with positive uptake were included. RCs between visits were calculated using the difference of the log of the average of the 2 reads for a reader at Day 1 and the log of the average of the 2 reads for the same reader at Week 6. The 95% RCs were calculated on the log-transformed data and exponentiated to determine the limits in percentages.
Time frame: Day 1 and Week 6
Population: The Image Evaluable Set was defined as all participants who underwent PET/CT scans on both Day 1 and 6 to 8 weeks after Day 1 and who had evaluable images at both time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Reader 1 | 14.58 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Reader 2 | 14.50 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Reader 3 | 12.97 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Reader 1 | 16.28 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Reader 2 | 9.46 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Reader 3 | 15.18 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Reader 1 | 14.38 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Reader 2 | 6.54 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Reader 3 | 7.97 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Reader 1 | 8.69 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Reader 2 | 9.64 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVmax) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Reader 3 | 8.39 coefficient of variation |
Primary
Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake
Between-visit repeatability of organ-specific (heart, kidney, liver, spleen) quantification (SUVpeak) of radiotracer uptake following PET/CT imaging of 124I-AT-01 in participants with AL or ATTR systemic amyloidosis was assessed. wCV with its associated 95% RC provides guidance on the level of change in organ-specific quantitation of radiotracer uptake that needs to be observed to be confident that a true change in uptake has occurred. Computation of wCV and associated RCs in addition to the two-sided 95% CI is described in the SAP. Only images from participants/organs with positive uptake were included. RCs between visits were calculated using the difference of the log of the average of the 2 reads for a reader at Day 1 and the log of the average of the 2 reads for the same reader at Week 6. The 95% RCs were calculated on the log-transformed data and exponentiated to determine the limits in percentages.
Time frame: Day 1 and Week 6
Population: The Image Evaluable Set was defined as all participants who underwent PET/CT scans on both Day 1 and 6 to 8 weeks after Day 1 and who had evaluable images at both time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Reader 1 | 13.06 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Reader 2 | 11.57 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Heart - Reader 3 | 8.21 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Reader 1 | 12.82 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Reader 2 | 9.95 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Kidney - Reader 3 | 13.88 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Reader 1 | 9.68 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Reader 2 | 8.37 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Liver - Reader 3 | 8.32 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Reader 1 | 12.47 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Reader 2 | 12.48 coefficient of variation |
| 124I-AT-01 | Within-Participant Coefficient of Variation [wCV] Associated With the Quantification (SUVpeak) of Radioactivity Associated With Organ-Level Radiotracer Uptake | Spleen - Reader 3 | 12.84 coefficient of variation |
Secondary
Change From Baseline in Anti-Drug Antibodies (ADA)
Changes from baseline in ADA
Time frame: Post-dose at Week 6 or Safety Follow-up 2 (28 days after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 124I-AT-01 | Change From Baseline in Anti-Drug Antibodies (ADA) | Negative for ADA at Screening and negative for ADA post-dose | 26 Participants |
| 124I-AT-01 | Change From Baseline in Anti-Drug Antibodies (ADA) | Negative for ADA at Screening and positive for ADA post-dose | 0 Participants |
Secondary
Change From Baseline in Vital Signs - Blood Pressure (mmHg)
Changes from baseline in blood pressure measurements with units of mmHg
Time frame: Day 1 post-administration and Week 6 pre-administration and post-administration
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Change From Baseline in Vital Signs - Blood Pressure (mmHg) | Systolic Blood Pressure - Day 1 Post-Administration | -2.8 mmHg | Standard Deviation 9.21 |
| 124I-AT-01 | Change From Baseline in Vital Signs - Blood Pressure (mmHg) | Systolic Blood Pressure - Week 6 Pre-Administration | -3.9 mmHg | Standard Deviation 15.97 |
| 124I-AT-01 | Change From Baseline in Vital Signs - Blood Pressure (mmHg) | Systolic Blood Pressure - Week 6 Post-Administration | -8.5 mmHg | Standard Deviation 16.98 |
| 124I-AT-01 | Change From Baseline in Vital Signs - Blood Pressure (mmHg) | Diastolic Blood Pressure - Day 1 Post-Administration | -3.2 mmHg | Standard Deviation 6.65 |
| 124I-AT-01 | Change From Baseline in Vital Signs - Blood Pressure (mmHg) | Diastolic Blood Pressure - Week 6 Pre-Administration | 0.2 mmHg | Standard Deviation 11.01 |
| 124I-AT-01 | Change From Baseline in Vital Signs - Blood Pressure (mmHg) | Diastolic Blood Pressure - Week 6 Post-Administration | -2.2 mmHg | Standard Deviation 11.45 |
Secondary
Change From Baseline in Vital Signs - Heart Rate (Beats/Min)
Changes from baseline in heart rate measurements with units of beats/min
Time frame: Day 1 post-administration and Week 6 pre-administration and post-administration
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Change From Baseline in Vital Signs - Heart Rate (Beats/Min) | Heart Rate - Day 1 Post-Administration | 1.1 beats/min | Standard Deviation 7.93 |
| 124I-AT-01 | Change From Baseline in Vital Signs - Heart Rate (Beats/Min) | Heart Rate - Week 6 Pre-Administration | 0.9 beats/min | Standard Deviation 7.37 |
| 124I-AT-01 | Change From Baseline in Vital Signs - Heart Rate (Beats/Min) | Heart Rate - Week 6 Post-Administration | 1.0 beats/min | Standard Deviation 7.21 |
Secondary
Clinical Laboratory Values - Chemistry (g/L)
Changes from baseline in chemistry clinical laboratory values with units of g/L
Time frame: At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (g/L) | Albumin - Week 6 | -0.4 g/L | Standard Deviation 2.79 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (g/L) | Albumin - Safety Follow-up 1 | -1.5 g/L | Standard Deviation 2.84 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (g/L) | Protein - Week 6 | -0.7 g/L | Standard Deviation 4.22 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (g/L) | Protein - Safety Follow-up 1 | -1.7 g/L | Standard Deviation 3.61 |
Secondary
Clinical Laboratory Values - Chemistry (IU/L)
Changes from baseline in chemistry clinical laboratory values with units of IU/L
Time frame: At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (IU/L) | Alanine Aminotransferase - Week 6 | -1.4 IU/L | Standard Deviation 9.54 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (IU/L) | Alanine Aminotransferase - Safety Follow-up 1 | -2.6 IU/L | Standard Deviation 8.03 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (IU/L) | Alkaline Phosphatase - Week 6 | -2.9 IU/L | Standard Deviation 13.2 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (IU/L) | Alkaline Phosphatase - Safety Follow-up 1 | -3.1 IU/L | Standard Deviation 12.46 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (IU/L) | Aspartate Aminotransferase - Week 6 | -0.3 IU/L | Standard Deviation 6.78 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (IU/L) | Aspartate Aminotransferase - Safety Follow-up 1 | -1.8 IU/L | Standard Deviation 5.64 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (IU/L) | Lactate Dehydrogenase - Week 6 | 1.1 IU/L | Standard Deviation 55.16 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (IU/L) | Lactate Dehydrogenase - Safety Follow-up 1 | -6.0 IU/L | Standard Deviation 49.7 |
Secondary
Clinical Laboratory Values - Chemistry (mmol/L)
Changes from baseline in chemistry clinical laboratory values with units of mmol/L
Time frame: At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Calcium - Week 6 | -0.028 mmol/L | Standard Deviation 0.1079 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Calcium - Safety Follow-up 1 | -0.035 mmol/L | Standard Deviation 1.1013 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Carbon Dioxide - Week 6 | -0.7 mmol/L | Standard Deviation 3.06 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Carbon Dioxide - Safety Follow-up 1 | -1.0 mmol/L | Standard Deviation 2.29 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Chloride - Week 6 | -0.9 mmol/L | Standard Deviation 2.65 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Chloride - Safety Follow-up 1 | 0.4 mmol/L | Standard Deviation 2.74 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Glucose - Week 6 | 0.3515 mmol/L | Standard Deviation 1.34157 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Glucose - Safety Follow-up 1 | 0.1310 mmol/L | Standard Deviation 1.63653 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Phosphate - Week 6 | 0.0025 mmol/L | Standard Deviation 0.1657 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Phosphate - Safety Follow-up 1 | 0.0229 mmol/L | Standard Deviation 0.16665 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Potassium - Week 6 | -0.11 mmol/L | Standard Deviation 0.462 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Potassium - Safety Follow-up 1 | 0.4 mmol/L | Standard Deviation 2.74 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Sodium - Week 6 | -0.2 mmol/L | Standard Deviation 3.32 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Sodium - Safety Follow-up 1 | 0.8 mmol/L | Standard Deviation 2.71 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Urea Nitrogen - Week 6 | 0.2116 mmol/L | Standard Deviation 1.81616 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (mmol/L) | Urea Nitrogen - Safety Follow-up 1 | -0.0429 mmol/L | Standard Deviation 2.17049 |
Secondary
Clinical Laboratory Values - Chemistry (Umol/L)
Changes from baseline in chemistry clinical laboratory values with units of umol/L
Time frame: At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (Umol/L) | Bilirubin - Week 6 | 1.0136 umol/L | Standard Deviation 4.00446 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (Umol/L) | Bilirubin - Safety Follow-up 1 | 1.2315 umol/L | Standard Deviation 2.44487 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (Umol/L) | Creatinine - Week 6 | 5.24 umol/L | Standard Deviation 18.541 |
| 124I-AT-01 | Clinical Laboratory Values - Chemistry (Umol/L) | Creatinine - Safety Follow-up 1 | 1.77 umol/L | Standard Deviation 14.43 |
Secondary
Clinical Laboratory Values - Hematology (10^12 Cells/L)
Changes from baseline in hematology clinical laboratory values with units of 10\^12 cells/L
Time frame: At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^12 Cells/L) | Erythrocytes - Week 6 | 0.000 10^12 cells/L | Standard Deviation 0.2684 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^12 Cells/L) | Erythrocytes - Safety Follow-up 1 | -0.055 10^12 cells/L | Standard Deviation 0.26 |
Secondary
Clinical Laboratory Values - Hematology (10^9 Cells/L)
Changes from baseline in hematology clinical laboratory values with units of 10\^9 cells/L
Time frame: At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Basophils - Week 6 | -0.02 10^9 cells/L | Standard Deviation 0.051 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Basophils - Safety Follow-up 1 | -0.03 10^9 cells/L | Standard Deviation 0.057 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Eosinophils - Week 6 | -0.02 10^9 cells/L | Standard Deviation 0.085 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Eosinophils - Safety Follow-up 1 | -0.01 10^9 cells/L | Standard Deviation 0.108 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Leukocytes - Week 6 | -0.27 10^9 cells/L | Standard Deviation 1.961 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Leukocytes - Safety Follow-up 1 | -0.29 10^9 cells/L | Standard Deviation 2.115 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Lymphocytes - Week 6 | -0.02 10^9 cells/L | Standard Deviation 0.314 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Lymphocytes - Safety Follow-up 1 | 0.02 10^9 cells/L | Standard Deviation 0.287 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Monocytes - Week 6 | -0.02 10^9 cells/L | Standard Deviation 0.208 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Monocytes - Safety Follow-up 1 | -0.06 10^9 cells/L | Standard Deviation 0.156 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Neutrophils - Week 6 | -0.22 10^9 cells/L | Standard Deviation 1.984 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Neutrophils - Safety Follow-up 1 | -0.21 10^9 cells/L | Standard Deviation 2.028 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Platelets - Week 6 | 4.4 10^9 cells/L | Standard Deviation 35.43 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (10^9 Cells/L) | Platelets - Safety Follow-up 1 | 3.1 10^9 cells/L | Standard Deviation 37.26 |
Secondary
Clinical Laboratory Values - Hematology (g/L)
Change from baseline in hematology clinical laboratory values with units of g/L
Time frame: At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Clinical Laboratory Values - Hematology (g/L) | Hemoglobin - Week 6 | -0.4 g/L | Standard Deviation 8.6 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (g/L) | Hemoglobin - Safety Follow-up 1 | -2.1 g/L | Standard Deviation 8.28 |
Secondary
Clinical Laboratory Values - Hematology (% of Total Blood Cell Count)
Changes from Baseline in hematology clinical laboratory values with units of % of total blood cell count
Time frame: At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of Total Blood Cell Count) | Hematocrit - Week 6 | -0.19 % of total blood cell count | Standard Deviation 2.554 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of Total Blood Cell Count) | Hematocrit - Safety Follow-up 1 | -0.54 % of total blood cell count | Standard Deviation 2.521 |
Secondary
Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count)
Changes from baseline in hematology clinical laboratory values with units of % of WBC count
Time frame: At Week 6 and Safety Follow-up 1 (24 to 48 hours after Week 6)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Basophils/Leukocytes - Week 6 | -0.1 % of WBC count | Standard Deviation 0.77 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Basophils/Leukocytes - Safety Follow-up 1 | -0.1 % of WBC count | Standard Deviation 0.81 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Eosinophils/Leukocytes - Week 6 | -0.2 % of WBC count | Standard Deviation 1.41 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Eosinophils/Leukocytes - Safety Follow-up 1 | -0.1 % of WBC count | Standard Deviation 1.72 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Lymphocytes/Leukocytes - Week 6 | 0.0 % of WBC count | Standard Deviation 6.62 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Lymphocytes/Leukocytes - Safety Follow-up 1 | 1.1 % of WBC count | Standard Deviation 6.32 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Monocytes/Leukocytes - Week 6 | -0.3 % of WBC count | Standard Deviation 4.57 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Monocytes/Leukocytes - Safety Follow-up 1 | -0.7 % of WBC count | Standard Deviation 4.68 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Neutrophils/Leukocytes - Week 6 | 0.6 % of WBC count | Standard Deviation 9.62 |
| 124I-AT-01 | Clinical Laboratory Values - Hematology (% of White Blood Cell [WBC] Count) | Neutrophils/Leukocytes - Safety Follow-up 1 | -0.1 % of WBC count | Standard Deviation 9.59 |
Secondary
Number of Participants With At Least 1 Treatment-Emergent Adverse Event (TEAE)
TEAEs were defined as events that were newly reported or reported to worsen in severity after the start of treatment. Adverse events (AEs) that occurred after the treatment start date, occurred on the treatment start date with a time that was equal to or after treatment start time, or that had a missing AE start date were categorized as treatment emergent.
Time frame: Day 1 through the end of the study (up to 14 weeks)
Population: The Safety Set was defined as all participants who received any amount of 124I-AT-01.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 124I-AT-01 | Number of Participants With At Least 1 Treatment-Emergent Adverse Event (TEAE) | 13 Participants |