Trial Outcomes & Findings for Biodistribution of 89Zirconium-labelled GSK2398852 Using PET Imaging (NCT NCT03417830)

Results Overview

SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented. All treated population consisted of all participants who received at least one Anti-SAP treatment including 89Zr-GSK2398852.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

2 participants

Primary outcome timeframe

Session 1: Days 4, 5, 6 and 8

Results posted on

2019-08-29

Participant Flow

This was a two part study. Part A contains two dosing sessions and Part B contain single dosing session. This study was conducted at a single center in Sweden from 06-April-18 to 20-July-2018.

Two participants were enrolled in Part A. The study was terminated by sponsor due to a change in the benefit:risk profile of GSK2315698+GSK2398852 (anti-serum amyloid P component \[SAP\] treatment) during Part A; hence, no participants were enrolled in Part B.

Participant milestones

Participant milestones
Measure	Part A: Anti-SAP Participants with either wild type or inherited transthyretin amyloidosis restrictive cardiomyopathy (ATTR-CM) were included. Participants underwent two dosing sessions. In each dosing session, participants were administered (dependent on renal function) 20 milligram (mg) per hour or 10 mg/hour GSK2315698 for 48 hours by one intravenous infusion; followed by administration of 70 mg(session1) or 490mg (session2) GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via two separate intravenous infusion on Day 3. Participants also received a subcutaneous injection of GSK2315698 60 mg thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 3 positron emission tomography (PET) scans were performed after the end of 89Zr-GSK2398852 infusion. There was a minimum of 4 weeks of duration between dosing sessions of anti-SAP mAb.	Part B: Anti-SAP Participants with either wild type or ATTR-CM were planned to undergo one dosing sessions. Participants were planned to be administered 200 mg/mL GSK2315698 via intravenous infusion for 48 hours followed by administration of 100 mg/mL GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via two separate intravenous infusion on Day 3. Participants were planned to receive a subcutaneous injection of GSK2315698 thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 2 PET scans were planned to be performed after the end of 89Zr-GSK2398852 infusion.
Part A (up to 26 Days) STARTED	2	0
Part A (up to 26 Days) COMPLETED	1	0
Part A (up to 26 Days) NOT COMPLETED	1	0
Part B (up to 26 Days) STARTED	0	0
Part B (up to 26 Days) COMPLETED	0	0
Part B (up to 26 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Anti-SAP Participants with either wild type or inherited transthyretin amyloidosis restrictive cardiomyopathy (ATTR-CM) were included. Participants underwent two dosing sessions. In each dosing session, participants were administered (dependent on renal function) 20 milligram (mg) per hour or 10 mg/hour GSK2315698 for 48 hours by one intravenous infusion; followed by administration of 70 mg(session1) or 490mg (session2) GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via two separate intravenous infusion on Day 3. Participants also received a subcutaneous injection of GSK2315698 60 mg thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 3 positron emission tomography (PET) scans were performed after the end of 89Zr-GSK2398852 infusion. There was a minimum of 4 weeks of duration between dosing sessions of anti-SAP mAb.	Part B: Anti-SAP Participants with either wild type or ATTR-CM were planned to undergo one dosing sessions. Participants were planned to be administered 200 mg/mL GSK2315698 via intravenous infusion for 48 hours followed by administration of 100 mg/mL GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via two separate intravenous infusion on Day 3. Participants were planned to receive a subcutaneous injection of GSK2315698 thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 2 PET scans were planned to be performed after the end of 89Zr-GSK2398852 infusion.
Part A (up to 26 Days) Study Closed/Terminated	1	0

Baseline Characteristics

Biodistribution of 89Zirconium-labelled GSK2398852 Using PET Imaging

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Anti-SAP n=2 Participants Participants with either wild type or ATTR-CM were included. Participants underwent two dosing sessions. In each dosing session, participants were administered (dependent on renal function) 20 mg per hour or 10 mg/hour GSK2315698 for 48 hours by one intravenous infusion; followed by administration of 70 mg (session1) or 490mg (session2) GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via two separate intravenous infusion on Day 3. Participants also received a subcutaneous injection of GSK2315698 60 mg thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 3 PET scans were performed after the end of 89Zr-GSK2398852 infusion. There was a minimum of 4 weeks of duration between dosing sessions of anti-SAP mAb.	Part B: Anti-SAP Participants with either wild type or ATTR-CM were planned to undergo one dosing sessions. Participants were planned to be administered 200 mg/mL GSK2315698 via intravenous infusion for 48 hours followed by administration of 100 mg/mL GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via two separate intravenous infusion on Day 3. Participants were planned to receive a subcutaneous injection of GSK2315698 thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 2 PET scans were planned to be performed after the end of 89Zr-GSK2398852 infusion.	Total n=2 Participants Total of all reporting groups
Age, Continuous	77.5 Years STANDARD_DEVIATION 3.54 • n=5 Participants	—	77.5 Years STANDARD_DEVIATION 3.54 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	—	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Session 1: Days 4, 5, 6 and 8

Population: All treated Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented. All treated population consisted of all participants who received at least one Anti-SAP treatment including 89Zr-GSK2398852.

Outcome measures

Outcome measures
Measure	Part A: Anti-SAP- Session 1 n=2 Participants Participants with either wild type or inherited ATTR-CM were included. In dosing session 1, participants were administered (dependent on renal function) 20 mg/hour or 10 mg/hour GSK2315698 for 48 hours by one intravenous infusion; followed by administration of 70 mg (session 1) GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via intravenous infusion on Day 3. Participants also received a subcutaneous injection of GSK2315698 60 mg thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 3 PET scans were performed after the end of 89Zr-GSK2398852 infusion.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool left ventricle,Day5,n=1	0.510 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool right ventricle,Day4,n=2	3.165 Grams per milliliter Standard Deviation 1.1526
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool right ventricle,Day5,n=1	1.050 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool right ventricle,Day6,n=1	0.950 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool right ventricle,Day8,n=1	1.240 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Left ventricle wall-high uptake,Day4,n=2	2.380 Grams per milliliter Standard Deviation 1.4425
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Left ventricle wall-high uptake,Day8,n=1	1.440 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Left ventricle wall-low uptake,Day4,n=2	1.740 Grams per milliliter Standard Deviation 1.4425
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Left ventricle wall-low uptake,Day5,n=1	0.700 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Left ventricle wall-low uptake,Day6,n=1	1.840 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Left ventricle wall-low uptake,Day8,n=1	0.760 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1: Mid septum-high uptake,Day4,n=2	2.335 Grams per milliliter Standard Deviation 1.2516
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1: Mid septum-high uptake,Day5,n=1	1.420 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1: Mid septum-high uptake,Day6,n=1	2.880 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1: Mid septum-high uptake,Day8,n=1	1.520 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1: Mid septum-low uptake,Day4,n=2	1.955 Grams per milliliter Standard Deviation 1.6051
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1: Mid septum-low uptake,Day5,n=1	0.780 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1: Mid septum-low uptake,Day6,n=1	2.230 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1: Mid septum-low uptake,Day8,n=1	0.610 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool left atrium,Day6,n=1	0.640 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool left atrium,Day8,n=1	0.400 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool left ventricle,Day4,n=2	2.800 Grams per milliliter Standard Deviation 1.5274
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool left ventricle,Day6,n=1	0.850 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool left ventricle,Day8,n=1	0.430 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Left ventricle wall-high uptake,Day5,n=1	1.290 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Left ventricle wall-high uptake,Day6,n=1	3.400 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool left atrium,Day4,n=2	2.995 Grams per milliliter Standard Deviation 1.4637
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb Session1:Blood pool left atrium,Day5,n=1	0.550 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.

PRIMARY outcome

Timeframe: Session 2: Days 3, 4 and 5

Population: All treated Population. Only those participants with data available at the specified data points were analyzed.

SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented.

Outcome measures

Outcome measures
Measure	Part A: Anti-SAP- Session 1 n=1 Participants Participants with either wild type or inherited ATTR-CM were included. In dosing session 1, participants were administered (dependent on renal function) 20 mg/hour or 10 mg/hour GSK2315698 for 48 hours by one intravenous infusion; followed by administration of 70 mg (session 1) GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via intravenous infusion on Day 3. Participants also received a subcutaneous injection of GSK2315698 60 mg thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 3 PET scans were performed after the end of 89Zr-GSK2398852 infusion.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Blood pool left atrium,Day3	10.290 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Blood pool left atrium,Day4	5.330 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Blood pool left atrium,Day5	3.550 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Blood pool left ventricle,Day3	10.120 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Blood pool left ventricle,Day4	4.910 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Blood pool left ventricle,Day5	3.110 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Blood pool right ventricle,Day3	10.390 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Blood pool right ventricle,Day4	5.160 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Blood pool right ventricle,Day5	3.500 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Left ventricle wall-high uptake,Day3	1.150 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Left ventricle wall-high uptake,Day4	4.540 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2: Left ventricle wall-high uptake,Day5	5.360 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Left ventricle wall-low uptake,Day3	3.110 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2:Left ventricle wall-low uptake,Day4	3.650 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2: Left ventricle wall-low uptake,Day5	3.980 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2: Mid septum-high uptake,Day3	4.680 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2: Mid septum-high uptake,Day4	4.200 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2: Mid septum-high uptake,Day5	4.780 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2: Mid septum-low uptake,Day3	3.580 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2: Mid septum-low uptake,Day4	3.570 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg Session2: Mid septum-low uptake,Day5	3.800 Grams per milliliter Standard Deviation NA Standard deviation could not be calculated as only one participant was analyzed.

SECONDARY outcome

Timeframe: Up to Day 26 of the last session

Population: Safety Population.

Urine samples were collected to analyze urinalysis parameters including glucose, protein, blood and ketones.

Outcome measures

Outcome measures
Measure	Part A: Anti-SAP- Session 1 n=2 Participants Participants with either wild type or inherited ATTR-CM were included. In dosing session 1, participants were administered (dependent on renal function) 20 mg/hour or 10 mg/hour GSK2315698 for 48 hours by one intravenous infusion; followed by administration of 70 mg (session 1) GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via intravenous infusion on Day 3. Participants also received a subcutaneous injection of GSK2315698 60 mg thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 3 PET scans were performed after the end of 89Zr-GSK2398852 infusion.
Part A: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones	2 Participants

SECONDARY outcome

Timeframe: Up to Day 26 of the last session

Population: Safety Population.

Urine samples were collected to analyze urinalysis parameters including specific gravity and potential of hydrogen.

Outcome measures

Outcome measures
Measure	Part A: Anti-SAP- Session 1 n=2 Participants Participants with either wild type or inherited ATTR-CM were included. In dosing session 1, participants were administered (dependent on renal function) 20 mg/hour or 10 mg/hour GSK2315698 for 48 hours by one intravenous infusion; followed by administration of 70 mg (session 1) GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via intravenous infusion on Day 3. Participants also received a subcutaneous injection of GSK2315698 60 mg thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 3 PET scans were performed after the end of 89Zr-GSK2398852 infusion.
Part A: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen	0 Participants

SECONDARY outcome

Timeframe: Up to Day 26

Population: Safety Population. Data was not collected as no participants were enrolled in Part B.

Urine samples were planned to be collected to analyze the urinalysis parameters.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Day 26

Population: Safety Population. Data was not collected as no participants were enrolled in Part B.

Urine samples were planned to be collected to analyze the urinalysis parameters.

Outcome measures

Outcome data not reported

Adverse Events

Part A: Anti-SAP

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Part A: Anti-SAP n=2 participants at risk Participants with either wild type or ATTR-CM were included. Participants underwent two dosing sessions. In each dosing session, participants were administered (dependent on renal function) 20 mg per hour or 10 mg/hour GSK2315698 for 48 hours by one intravenous infusion; followed by administration of 70 mg (session1) or 490mg (session2) GSK2398852 (unlabelled anti-SAP mAb) together with 10 mg of 89Zr-GSK2398852 (up to 37 megabecquerel of radioactive dose) via two separate intravenous infusion on Day 3. Participants also received a subcutaneous injection of GSK2315698 60 mg thrice daily for up to 8 days after administration of unlabelled anti-SAP mAb dose. Up to 3 PET scans were performed after the end of 89Zr-GSK2398852 infusion. There was a minimum of 4 weeks of duration between dosing sessions of anti-SAP mAb.
Nervous system disorders Headache	100.0% 2/2 • Number of events 2 • AEs and SAEs were collected up to Day 26 of the last session Safety population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852. AEs and SAEs were not collected in Part B as no participants were enrolled. Data is presented for Part A only as data was not collected in Part B due to the study was terminated during Part A, and Part B was not initiated.
Nervous system disorders Restless legs syndrome	50.0% 1/2 • Number of events 1 • AEs and SAEs were collected up to Day 26 of the last session Safety population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852. AEs and SAEs were not collected in Part B as no participants were enrolled. Data is presented for Part A only as data was not collected in Part B due to the study was terminated during Part A, and Part B was not initiated.
Eye disorders Dry eye	50.0% 1/2 • Number of events 1 • AEs and SAEs were collected up to Day 26 of the last session Safety population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852. AEs and SAEs were not collected in Part B as no participants were enrolled. Data is presented for Part A only as data was not collected in Part B due to the study was terminated during Part A, and Part B was not initiated.
Gastrointestinal disorders Diarrhoea	50.0% 1/2 • Number of events 1 • AEs and SAEs were collected up to Day 26 of the last session Safety population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852. AEs and SAEs were not collected in Part B as no participants were enrolled. Data is presented for Part A only as data was not collected in Part B due to the study was terminated during Part A, and Part B was not initiated.
General disorders Injection site bruising	50.0% 1/2 • Number of events 1 • AEs and SAEs were collected up to Day 26 of the last session Safety population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852. AEs and SAEs were not collected in Part B as no participants were enrolled. Data is presented for Part A only as data was not collected in Part B due to the study was terminated during Part A, and Part B was not initiated.
Musculoskeletal and connective tissue disorders Dactylitis	50.0% 1/2 • Number of events 1 • AEs and SAEs were collected up to Day 26 of the last session Safety population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852. AEs and SAEs were not collected in Part B as no participants were enrolled. Data is presented for Part A only as data was not collected in Part B due to the study was terminated during Part A, and Part B was not initiated.
Skin and subcutaneous tissue disorders Urticarial vasculitis	50.0% 1/2 • Number of events 1 • AEs and SAEs were collected up to Day 26 of the last session Safety population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852. AEs and SAEs were not collected in Part B as no participants were enrolled. Data is presented for Part A only as data was not collected in Part B due to the study was terminated during Part A, and Part B was not initiated.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER