A Safety Study of GSK3039294 in Healthy Volunteers and Patients With Systemic Amyloidosis

Study at a glance

From the registry record, last updated by the sponsor on 23 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Three-part Open-label, Non-randomised, Dose-escalation Study to Investigate the Safety and Tolerability of GSK3039294 Administered as a Single Dose to Healthy Volunteers, and as Repeat Dose to Healthy Volunteers and Patients With Systemic Amyloidosis

ClinicalTrials.gov ID

NCT02603172

Acronym / sponsor ID

201664

Conditions

Amyloidosis

Keywords

GSK3039294, GSK2315698, systemic amyloidosis, CPHPC, dose-escalation

Phase

Phase 1

Study type

Interventional

Recruitment status

TerminatedReason stopped: A new study will be initiated in order to specifically investigate cardiac safety

Enrolment

23 participants (actual)

Lead sponsor

GlaxoSmithKlineIndustry (pharma, biotech, devices)

Study start

12 May 2016 (actual)

Primary completion

10 May 2017 (actual)

Study completion

10 May 2017 (actual)

First posted

11 Nov 2015 (estimated)

Results

Posted 23 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Non-randomised

Intervention model

Parallel groups

Masking

None (open label)

Number of arms

5

Who may qualify

Ages

18 to 70 years

Sex

All

Healthy volunteers

Accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Part A:Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

   Time frame: Up to Day 14

   An AE is any untoward medical occurrence in a participants or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization clinical chemor prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other important medical events judged by the investigator that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention. Safety population consist of all participants who received at least one dose of the study medication.

2. Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria

   Time frame: Day 1

   PCI ranges for the clinical chemistry parameters were as follows : albumin (low: <0.86 gram [g] per liter [L]), calcium (low: <0.91 millimole [mmol]/L and high: >1.06 mmol/L), glucose (low: <0.71 mmol/L and high: >1.41 mmol/L), magnesium (low: <0.63 mmol/L and high: >1.03 mmol/L), phosphorous (low: <0.80 mmol/L and high: >1.14 mmol/L), potassium (low: <0.86 mmol/L and high: >1.10 mmol/L), sodium (low: <0.96 mmol/L and high: >1.03 mmol/L), and total carbon dioxide (CO2) (low: <0.86 mmol/L and high: >1.14 mmol/L).

3. Part A: Number of Participants With Emergent Hematology by PCI Criteria

   Time frame: Day 1

   PCI ranges for the hematology parameters were as follows: white blood cell (WBC) count (low: <0.67 10^9 cells/L and high: >1.82 10^9 cells/L), neutrophil count (low: <0.83 10^9 cells/L), hemoglobin (high: >1.03 g/L in male, >1.13 g/L in female), hemocrit (high: >1.02 proportion of red blood cell [RBC] in blood for male, >1.17 proportion of RBC in blood for female), platelet count (low: <0.67 10^9 cells/L and high: 1.57 10^9 cells/L), and lymphocytes (low: <0.81 10^9 cells/L).

4. Part A: Number of Participants With Abnormal Urinalysis Data by Dipstick

   Time frame: Day 1

   Urine samples were collected and urinalysis included analysis of specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones by dipstick. The dipstick test gives results in a semi-quantitative manner.

5. Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG)

   Time frame: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

   Triplicate ECG was measured in semi-supine position after 5 minutes (min) rest. A single 12-lead ECG was measured by using ECG machine that automatically measured PR, QRS, QT, and Fridericia's formula (QTcF) intervals. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

6. Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG

   Time frame: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

   Triplicate ECG was measured in semi-supine position after 5 min rest. A single 12-lead ECG was measured by using ECG machine that automatically measures the heart rate. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

7. Part A: Mean Change From Baseline in Blood Pressure (BP)

   Time frame: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

   Systolic BP and diastolic BP were measured in semi-supine position after 5 min rest for the participants at indicated time points. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

8. Part A: Mean Change From Baseline in Pulse Rate

   Time frame: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

   Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

9. Part A: Mean Change From Baseline in Temperature

   Time frame: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

   Temperature was measured in semi-supine position after 5 min rest for the participants at indicated time points. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

10. Part B:Number of Participants With AEs and SAEs

    Time frame: Cohort 3: Up to Day 21; Cohort 4: Up to Day 35

    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other important medical events judged by the investigator that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention.

11. Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria

    Time frame: Cohort 3 and 4: Up to Day 3

    PCI ranges for the clinical chemistry parameters were as follows: albumin (low: <0.86 g/L), calcium (low: <0.91 mmol/L and high: >1.06 mmol/L), glucose (low: <0.71 mmol/L and high: >1.41 mmol/L), magnesium (low: <0.63 mmol/L and high: >1.03 mmol/L), phosphorous (low: <0.80 mmol/L and high: >1.14 mmol/L), potassium (low: <0.86 mmol/L and high: >1.10 mmol/L), sodium (low: <0.96 mmol/L and high: >1.03 mmol/L), and total CO2 (low: <0.86 mmol/L and high: >1.14 mmol/L).

12. Part B: Number of Participants With Emergent Hematology by PCI Criteria

    Time frame: Cohort 3 and 4: Up to Day 3

    PCI ranges for the hematology parameters were as follows: WBC count (low: <0.67 10^9 cells/L and high: >1.82 10^9 cells/L), neutrophil count (low: <0.83 10^9 cells/L), hemoglobin (high: >1.03 g/L in male, >1.13 g/L in female), hemocrit (high: >1.02 proportion of RBC in blood for male, >1.17 proportion of RBC in blood for female), platelet count (low: <0.67 10^9 cells/L and high: 1.57 10^9 cells/L), and lymphocytes (low: <0.81 10^9 cells/L).

13. Part B: Number of Participants With Abnormal Urinalysis Data by Dipstick

    Time frame: Cohort 3 and 4: Up to Day 3

    Urine samples were collected and urinalysis included analysis of specific gravity, pH, glucose, protein, blood, ketones by dipstick. The dipstick test gives results in a semi-quantitative manner.

14. Part B: Mean Change From Baseline in 12-lead ECG

    Time frame: Cohort 3: Baseline (pre-dose), Day 1 (1 hour), Days 2, 3, 4, 5, 6, 7 (pre-dose and 1 hour), 8 and 21; Cohort 4: Up to Day 35

    Triplicate ECG was measured in semi-supine position after 5 minutes rest. A single 12-lead ECG was measured by using ECG machine that automatically measured PR, QRS, QT, and QTcF intervals. Baseline is defined as the latest available assessment pre the first dose of study drug in Part B. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

15. Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG

    Time frame: Cohort 3: Baseline (pre-dose), Day 1 (1 hour), Days 2, 3, 4, 5, 6, 7 (pre-dose and 1 hour), 8 and 21; Cohort 4: Up to Day 35

    Triplicate ECG was measured in semi-supine position after 5 min rest. A single 12-lead ECG was measured by using ECG machine that automatically measures heart rate. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part B. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

16. Part B: Number of Participants With Abnormal Cardiac Telemetry Findings

    Time frame: Cohort 3: Up to Day 8

    The cardiac monitoring was measured by using an appropriate nonimplantable recording device which is acceptable to the participants. This was evaluated the arrhythmic background of eligible cardiac amyloidosis participants such that false positive attribution of arrhythmias to GSK3039294 during repeat dosing was minimized.

17. Part C: Number of Participants With AEs and SAEs

    Time frame: Up to Day 63

    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other important medical events judged by the investigator that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

18. Part C: Number of Participants With Emergent Clinical Chemistry by PCI Criteria

    Time frame: Up to Day 63

    PCI parameters for the clinical chemistry that were planned for analysis are as follows: albumin, calcium, glucose, magnesium, phosphorous , potassium , sodium , and total CO2. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

19. Part C: Number of Participants With Emergent Hematology Parameters by PCI Criteria

    Time frame: Up to Day 63

    Hematology parameters that were planned for analysis were as follows: WBC count , neutrophil count , hemoglobin , hemocrit , platelet count , and lymphocytes. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

20. Part C: Number of Participants With Emergent Urinalysis Parameters by PCI Criteria

    Time frame: Up to Day 63

    Urine samples were planned to be collected and urinalysis included analysis of specific gravity, pH, glucose, protein, blood, ketones by dipstick. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

21. Part C: Number of Participants With Abnormal 12-lead ECG Findings

    Time frame: Up to Day 35

    Triplicate ECG was planned to be measured in semi-supine position after 5 minutes rest. A single 12-lead ECG was measured by using ECG machine that automatically measured PR, QRS, QT, and QTcF intervals. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part C. Change from Baseline was calculated as any visit post Baseline value minus Baseline value. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

22. Part C: Number of Participants With Abnormal Vital Signs

    Time frame: Up to Day 35

    Vital signs included systolic and diastolic BP, pulse rate, heart rate and temperature. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

23. Part C: Number of Participants With Abnormal Cardiac Telemetry Findings

    Time frame: Up to Day 35

    The cardiac monitoring was planned to be measured by using an appropriate nonimplantable recording device which is acceptable to the participants. This was evaluated the arrhythmic background of eligible cardiac amyloidosis participants such that false positive attribution of arrhythmias to GSK3039294 during repeat dosing was minimized. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2019.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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