Coronary Heart Disease (CHD)
Conditions
Keywords
Coronary Heart Disease, Atherosclerosis
Brief summary
A Phase IIB Parallel group Study to Evaluate the Efficacy and Safety of MEDI6570 in Participants with a Prior Myocardial Infarction.
Detailed description
This Phase IIB, proof-of-concept, dose-range finding clinical study is being conducted to evaluate the anti-inflammatory potential of MEDI6570 and its effect on surrogates for atherosclerotic and heart failure (HF) events in patients with a history of myocardial infarction (MI). The results of the Phase IIB study will inform future clinical development options and precision medicine strategy for future clinical studies. Participants will be randomized in a 2:2:1:1 ratio after protocol Amend 2, 360 evaluable participants (111 evaluable participants in each of the 2 MEDI6570 groups, plus 27 evaluable participants in the legacy low dose MEDI6570 group, plus 111 participants in pooled placebo) will complete the study.
Interventions
BIOLOGICALMEDI6570
MEDI6570
BIOLOGICALPlacebo
Buffer
Sponsors
The TIMI Study Group
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant must provide informed consent before any study specific activities are performed, must be able and willing to meet all requirements for randomization within 42 days after signing the full ICF, and must adhere to the schedules of activities. 2. Women must be ≥ 40 years of age at the time of signing the ICF. Men must be ≥ 21 years of age at the time of signing the ICF. 3. Participant must: 1. be 30 to 365 days after presumed type-1 (ie, due to plaque rupture or erosion) MI (either STEMI or NSTEMI) at the time of enrollment. 2. have persistent inflammation, defined as hs CRP ≥ 1 mg/L, as measured centrally at screening Visit 1. 4. Participant must have body mass index within the range 18 to 40 kg/m2 inclusive. 5. For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential, confirmed at screening Visit 1 by one of the following: 1. Postmenopausal, defined as amenorrhea for ≥ 12 months following cessation of all exogenous hormonal treatments, and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range. 2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization. 6. Participant must have an evaluable, pre-randomization CTA with quantifiable, non calcified plaque.
Exclusion criteria
1. History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study. 2. Percutaneous coronary intervention or diagnostic angiogram planned after screening. Eligible participants who have a diagnostic angiogram performed in the absence of undergoing a new PCI may continue screening after the diagnostic angiogram has been performed or may be rescreened. 3. History of or planned coronary artery bypass grafting. 4. Documented episode of post-MI pericarditis in the 3 months before enrollment. 5. Ongoing New York Heart Association Class IV HF. 6. Increased risk of bleeding 1. Patients with history or presence of any bleeding disorder. 2. Signs of ongoing bleeding at screening (eg, identified macroscopic bleeding, low hemoglobin presumed to be caused by bleeding) or high risk for major bleeding in accordance with the Investigator's assessment. 3. Need for chronic therapeutic anticoagulation therapy anticipated to be required throughout the course of the study (short-term treatment with prophylactic doses of heparin/low molecular weight heparin are allowed). 4. Known severe liver disease. 7. History or presence of any of the following: 1. Ongoing infection or febrile illness that in the opinion of the investigator may be the cause of elevated hs-CRP on screening. 2. Ongoing atrial fibrillation or flutter. 3. Cancer within 5 years before randomization, with the exception of non melanoma skin cancer. 4. Alcohol or substance abuse within 6 months before randomization, as judged by the investigator. 5. Known history of hypersensitivity reactions to other biologics, to human IgG preparations, or to any component of MEDI6570, or ongoing severe allergy as judged by the investigator. 6. Patients with active positive results on screening for serum hepatitis B surface antigen, hepatitis C antibody, or HIV. 8. Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, as judged by the investigator. 9. BP values at screening: 1. Systolic BP \< 90 mmHg or \> 180 mmHg. 2. Diastolic BP \> 100 mmHg. 3. Participants who are excluded based on elevated BP may be rescreened following adequate treatment. 10. Participants with any of the following contraindications to CTA: 1. eGFR \< 50 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation, or end stage renal disease treated with kidney transplant or renal replacement therapy. 2. Allergy to iodinated contrast. 3. History of contrast-induced nephropathy. 4. Contraindication to nitroglycerin. 5. Rapid heart rate that is uncontrolled by medical therapy. 6. Inability to hold breath for at least 6 seconds. 11. Receipt of any investigational device or therapy within 6 months or 5 half lives before screening (whichever is longer). This criterion does NOT apply for inactive, non replicating COVID-19 vaccines approved by Health Authorities or under emergency use authorization. 12. Planned participation in an additional investigational study of an intervention or biologic before the end of the follow-up period. Participation in observational studies or studies without investigational drugs or devices is allowed. 13. Participants who are legally institutionalized. 14. An employee or close relative of an employee of the sponsor, the CRO, or the study site, regardless of the employee or close relative's role.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging | From baseline to Day 253 | To evaluate the effect of MEDI6570 on non-calcified coronary atherosclerotic plaques compared with placebo. The primary endpoint of change in NCPVMD from baseline to Day 253 was assessed based on the CTA Analysis Populations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF) | From baseline to Day 253 | To evaluate the effect of MEDI6570 on left ventricular systolic function compared with placebo |
| Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | From baseline to Day 253 | To evaluate the effect of MEDI6570 on left ventricular systolic function among participants with reduced ejection fraction (defined as \<50%) compared with placebo |
| Change From Baseline to Day 253 in Global Longitudinal Strain (GLS) | From baseline to Day 253 | To evaluate the effect of MEDI6570 on left ventricular systolic function compared with placebo |
| Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | From baseline to Day 253 | To evaluate the effect of MEDI6570 on left ventricular systolic function among participants with reduced ejection fraction (defined as \<50%) compared with placebo |
| Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV) | From baseline to Day 253 | To evaluate the effect of MEDI6570 on other measures of non-calcified coronary atherosclerotic plaque compared with placebo |
| Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV) | From baseline to Day 253 | To evaluate the effect of MEDI6570 on other measures of non-calcified coronary atherosclerotic plaque compared with placebo |
| Summary of ADA (Anti-drug Antibody) Responses During the Study | From baseline to Day 325/405. Day 325/405: for participants who completed the study under clinical study protocol (CSP) Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively. | To evaluate the immunogenicity of MEDI6570 |
| Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) | From baseline to Day 253 | To evaluate the effect of MEDI6570 on a surrogate biomarker of Heart Failure (HF) compared with placebo |
| Summary of Serum Concentrations (ug/mL) of MEDI6570 | From baseline to Day 325/Day 405 | MEDI6570 concentrations as measured in serum during the intervention and follow-up periods |
| Number of Participants With Adverse Events in Any Category | During study follow-up (from day 1 to day 325) | To assess the safety and tolerability of MEDI6570 compared with placebo |
| Number of Participants With Most Common Adverse Events (Frequency > 5%) | During study follow-up (from day 1 to day 325) | To assess the safety and tolerability of MEDI6570 compared with placebo |
| Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively. | To assess the safety and tolerability of MEDI6570 compared with placebo |
| Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively. | To assess the safety and tolerability of MEDI6570 compared with placebo |
| Vital Signs (Change of Weight From Baseline to Day 325/405 ) | From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively | To assess the safety and tolerability of MEDI6570 compared with placebo |
| Anti-drug Antibody Titre Summary by Visit | From Baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively. | To evaluate the immunogenicity of MEDI6570 |
Countries
Australia, Canada, Czechia, Hungary, Italy, Japan, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MEDI6570 50 mg Participants received MEDI6570 50 mg every 4 weeks for 32 weeks | 40 |
| MEDI6570 150 mg Participants received MEDI6570 150 mg every 4 weeks for 32 weeks | 129 |
| MEDI6570 400 mg Participants received MEDI6570 400 mg every 4 weeks for 32 weeks | 126 |
| Placebo Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks | 128 |
| Total | 423 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 1 | 3 |
| Overall Study | Death | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Subjects who did not receive treatment | 1 | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 0 | 6 | 6 |
Baseline characteristics
| Characteristic | Total | MEDI6570 50 mg | MEDI6570 150 mg | MEDI6570 400 mg | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 59.9 Years STANDARD_DEVIATION 9.3 | 60.1 Years STANDARD_DEVIATION 8.3 | 59.9 Years STANDARD_DEVIATION 9.2 | 59.4 Years STANDARD_DEVIATION 9.6 | 60.4 Years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 5 Participants | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 404 Participants | 35 Participants | 124 Participants | 124 Participants | 121 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized ASIAN | 34 Participants | 7 Participants | 10 Participants | 8 Participants | 9 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 385 Participants | 33 Participants | 116 Participants | 118 Participants | 118 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Non-caucasian | 38 Participants | 7 Participants | 13 Participants | 8 Participants | 10 Participants |
| Race/Ethnicity, Customized OTHER | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized WHITE | 385 Participants | 33 Participants | 116 Participants | 118 Participants | 118 Participants |
| Region of Enrollment Australia | 15 Participants | 0 Participants | 6 Participants | 6 Participants | 3 Participants |
| Region of Enrollment Canada | 4 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Czech Republic | 54 Participants | 2 Participants | 17 Participants | 17 Participants | 18 Participants |
| Region of Enrollment Hungary | 55 Participants | 9 Participants | 11 Participants | 12 Participants | 23 Participants |
| Region of Enrollment Italy | 54 Participants | 0 Participants | 14 Participants | 21 Participants | 19 Participants |
| Region of Enrollment Japan | 32 Participants | 7 Participants | 9 Participants | 8 Participants | 8 Participants |
| Region of Enrollment Netherlands | 41 Participants | 1 Participants | 18 Participants | 11 Participants | 11 Participants |
| Region of Enrollment Poland | 40 Participants | 2 Participants | 14 Participants | 14 Participants | 10 Participants |
| Region of Enrollment Spain | 69 Participants | 13 Participants | 20 Participants | 18 Participants | 18 Participants |
| Region of Enrollment United Kingdom | 11 Participants | 0 Participants | 5 Participants | 5 Participants | 1 Participants |
| Region of Enrollment United States of America | 48 Participants | 6 Participants | 12 Participants | 13 Participants | 17 Participants |
| Sex: Female, Male Female | 75 Participants | 12 Participants | 19 Participants | 23 Participants | 21 Participants |
| Sex: Female, Male Male | 348 Participants | 28 Participants | 110 Participants | 103 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 1 / 129 | 1 / 126 | 0 / 126 |
| other Total, other adverse events | 15 / 39 | 33 / 129 | 37 / 126 | 23 / 126 |
| serious Total, serious adverse events | 4 / 39 | 17 / 129 | 10 / 126 | 13 / 126 |
Outcome results
Primary
Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging
To evaluate the effect of MEDI6570 on non-calcified coronary atherosclerotic plaques compared with placebo. The primary endpoint of change in NCPVMD from baseline to Day 253 was assessed based on the CTA Analysis Populations.
Time frame: From baseline to Day 253
Population: Participants within the Intention To Treat (ITT) Population who had interpretable CTA scans at baseline and at Day 253. Participants were analyzed according to their randomized treatment group.~Subjects initially randomized to the 250 mg group switched dose to 400 mg following clinical study protocol (CSP) amendment 1 and were analysed according to the 400 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MEDI6570 50 mg | Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging | -15.3220 mm^3 | Standard Error 4.9219 |
| MEDI6570 150 mg | Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging | -4.5509 mm^3 | Standard Error 3.1654 |
| MEDI6570 400 mg | Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging | -6.3658 mm^3 | Standard Error 3.2559 |
| MEDI6570 150 mg or 400 mg | Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging | -5.4220 mm^3 | Standard Error 2.6622 |
| Placebo | Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging | -6.9424 mm^3 | Standard Error 3.2729 |
p-value: 0.68590% CI: [-3.6657, 6.7064]ANCOVA
p-value: 0.06590% CI: [-17.498, 0.7387]ANCOVA
p-value: 0.74790% CI: [-3.5338, 8.3167]ANCOVA
p-value: 0.56390% CI: [-5.4389, 6.5921]ANCOVA
Secondary
Anti-drug Antibody Titre Summary by Visit
To evaluate the immunogenicity of MEDI6570
Time frame: From Baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.
Population: Subjects included in the As-treated Population who have ≥ 1 immunogenicity sample will be included in the Immunogenicity Population. Subjects will be analysed according to the actual treatment they received. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MEDI6570 50 mg | Anti-drug Antibody Titre Summary by Visit | Day 325/405 | 120.0 Titer units |
| MEDI6570 50 mg | Anti-drug Antibody Titre Summary by Visit | Day 113 | 640 Titer units |
| MEDI6570 50 mg | Anti-drug Antibody Titre Summary by Visit | Day 253 | 160 Titer units |
| MEDI6570 50 mg | Anti-drug Antibody Titre Summary by Visit | Day 169 | 320 Titer units |
| MEDI6570 150 mg | Anti-drug Antibody Titre Summary by Visit | Baseline | 80 Titer units |
| MEDI6570 150 mg | Anti-drug Antibody Titre Summary by Visit | Day 29 | 640 Titer units |
| MEDI6570 150 mg | Anti-drug Antibody Titre Summary by Visit | Day 57 | 80 Titer units |
| MEDI6570 150 mg | Anti-drug Antibody Titre Summary by Visit | Day 113 | 640 Titer units |
| MEDI6570 150 mg | Anti-drug Antibody Titre Summary by Visit | Day 169 | 1600 Titer units |
| MEDI6570 150 mg | Anti-drug Antibody Titre Summary by Visit | Day 253 | 1360 Titer units |
| MEDI6570 150 mg | Anti-drug Antibody Titre Summary by Visit | Day 325/405 | 320 Titer units |
| MEDI6570 400 mg | Anti-drug Antibody Titre Summary by Visit | Day 325/405 | 80 Titer units |
| MEDI6570 400 mg | Anti-drug Antibody Titre Summary by Visit | Day 253 | 80 Titer units |
| MEDI6570 400 mg | Anti-drug Antibody Titre Summary by Visit | Baseline | 320 Titer units |
| MEDI6570 150 mg or 400 mg | Anti-drug Antibody Titre Summary by Visit | Day 253 | 160 Titer units |
| MEDI6570 150 mg or 400 mg | Anti-drug Antibody Titre Summary by Visit | Day 29 | 640 Titer units |
| MEDI6570 150 mg or 400 mg | Anti-drug Antibody Titre Summary by Visit | Baseline | 200 Titer units |
| MEDI6570 150 mg or 400 mg | Anti-drug Antibody Titre Summary by Visit | Day 325/405 | 160 Titer units |
| MEDI6570 150 mg or 400 mg | Anti-drug Antibody Titre Summary by Visit | Day 57 | 80 Titer units |
| MEDI6570 150 mg or 400 mg | Anti-drug Antibody Titre Summary by Visit | Day 113 | 640 Titer units |
| MEDI6570 150 mg or 400 mg | Anti-drug Antibody Titre Summary by Visit | Day 169 | 640 Titer units |
| Placebo | Anti-drug Antibody Titre Summary by Visit | Day 325/405 | NA Titer units |
| Total | Anti-drug Antibody Titre Summary by Visit | Day 113 | 640 Titer units |
| Total | Anti-drug Antibody Titre Summary by Visit | Day 169 | 640.0 Titer units |
| Total | Anti-drug Antibody Titre Summary by Visit | Day 57 | 80 Titer units |
| Total | Anti-drug Antibody Titre Summary by Visit | Day 253 | 160 Titer units |
| Total | Anti-drug Antibody Titre Summary by Visit | Day 29 | 640 Titer units |
| Total | Anti-drug Antibody Titre Summary by Visit | Day 325/405 | 160 Titer units |
| Total | Anti-drug Antibody Titre Summary by Visit | Baseline | 200 Titer units |
Secondary
Change From Baseline to Day 253 in Global Longitudinal Strain (GLS)
To evaluate the effect of MEDI6570 on left ventricular systolic function compared with placebo
Time frame: From baseline to Day 253
Population: Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MEDI6570 50 mg | Change From Baseline to Day 253 in Global Longitudinal Strain (GLS) | -1.20 Percentage of GLS | Standard Error 0.56 |
| MEDI6570 150 mg | Change From Baseline to Day 253 in Global Longitudinal Strain (GLS) | -0.70 Percentage of GLS | Standard Error 0.35 |
| MEDI6570 400 mg | Change From Baseline to Day 253 in Global Longitudinal Strain (GLS) | -0.77 Percentage of GLS | Standard Error 0.35 |
| MEDI6570 150 mg or 400 mg | Change From Baseline to Day 253 in Global Longitudinal Strain (GLS) | -0.74 Percentage of GLS | Standard Error 0.29 |
| Placebo | Change From Baseline to Day 253 in Global Longitudinal Strain (GLS) | 0.09 Percentage of GLS | Standard Error 0.35 |
p-value: 0.98190% CI: [-2.32, -0.27]ANCOVA
p-value: 0.97490% CI: [-1.47, -0.12]ANCOVA
p-value: 0.98390% CI: [-1.53, -0.2]ANCOVA
p-value: 0.9990% CI: [-1.42, -0.25]ANCOVA
Secondary
Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV)
To evaluate the effect of MEDI6570 on other measures of non-calcified coronary atherosclerotic plaque compared with placebo
Time frame: From baseline to Day 253
Population: Participants within the ITT Population who had interpretable b CTA scans at baseline and at Day 253 or at Day 122 were included. (Note that separate analyses were conducted for Day 253 and Day 122). Participants were analyzed according to their randomized treatment group.~Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MEDI6570 50 mg | Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV) | -26.4453 mm^3 | Standard Error 10.0524 |
| MEDI6570 150 mg | Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV) | -10.9010 mm^3 | Standard Error 6.4671 |
| MEDI6570 400 mg | Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV) | -10.4850 mm^3 | Standard Error 6.6607 |
| MEDI6570 150 mg or 400 mg | Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV) | -10.7013 mm^3 | Standard Error 5.4415 |
| Placebo | Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV) | -10.3083 mm^3 | Standard Error 6.7052 |
p-value: 0.07790% CI: [-34.7829, 2.5089]ANCOVA
p-value: 0.46890% CI: [-12.7267, 11.5413]ANCOVA
p-value: 0.49190% CI: [-12.4678, 12.1144]ANCOVA
p-value: 0.47690% CI: [-11.0022, 10.2162]ANCOVA
Secondary
Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF)
To evaluate the effect of MEDI6570 on left ventricular systolic function compared with placebo
Time frame: From baseline to Day 253
Population: Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MEDI6570 50 mg | Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF) | -0.91 Percentage of LVEF | Standard Error 0.55 |
| MEDI6570 150 mg | Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF) | 0.32 Percentage of LVEF | Standard Error 0.34 |
| MEDI6570 400 mg | Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF) | 0.11 Percentage of LVEF | Standard Error 0.35 |
| MEDI6570 150 mg or 400 mg | Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF) | 0.22 Percentage of LVEF | Standard Error 0.28 |
| Placebo | Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF) | 0.53 Percentage of LVEF | Standard Error 0.35 |
p-value: 0.9990% CI: [-2.44, -0.43]ANCOVA
p-value: 0.69790% CI: [-0.87, 0.45]ANCOVA
p-value: 0.84990% CI: [-1.08, 0.25]ANCOVA
p-value: 0.81190% CI: [-0.89, 0.27]ANCOVA
Secondary
Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV)
To evaluate the effect of MEDI6570 on other measures of non-calcified coronary atherosclerotic plaque compared with placebo
Time frame: From baseline to Day 253
Population: Participants within the ITT Population who had interpretable CTA scans at baseline and at Day 253. Participants were analyzed according to their randomized treatment group.~Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MEDI6570 50 mg | Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV) | -7.9167 mm3 | Standard Error 3.5226 |
| MEDI6570 150 mg | Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV) | -4.8101 mm3 | Standard Error 2.269 |
| MEDI6570 400 mg | Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV) | -4.2748 mm3 | Standard Error 2.3363 |
| MEDI6570 150 mg or 400 mg | Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV) | -4.5532 mm3 | Standard Error 1.9099 |
| Placebo | Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV) | -3.5733 mm3 | Standard Error 2.3481 |
p-value: 0.13690% CI: [-10.8637, 2.1768]ANCOVA
p-value: 0.31690% CI: [-5.4796, 3.0059]ANCOVA
p-value: 0.39490% CI: [-5.0096, 3.6065]ANCOVA
p-value: 0.33290% CI: [-4.6927, 2.7329]ANCOVA
Secondary
Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP)
To evaluate the effect of MEDI6570 on a surrogate biomarker of Heart Failure (HF) compared with placebo
Time frame: From baseline to Day 253
Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MEDI6570 50 mg | Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) | 0.8226 pg/mL | Geometric Coefficient of Variation 9.4 |
| MEDI6570 150 mg | Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) | 0.7787 pg/mL | Geometric Coefficient of Variation 5.5 |
| MEDI6570 400 mg | Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) | 0.7368 pg/mL | Geometric Coefficient of Variation 5.6 |
| MEDI6570 150 mg or 400 mg | Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) | 0.7575 pg/mL | Geometric Coefficient of Variation 4.4 |
| Placebo | Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) | 0.7370 pg/mL | Geometric Coefficient of Variation 5.6 |
p-value: 0.85490% CI: [0.94, 1.33]Mixed model with repeated measurements
p-value: 0.7990% CI: [0.94, 1.18]Mixed model with repeated measurements
p-value: 0.49890% CI: [0.89, 1.12]Mixed model with repeated measurements
p-value: 0.67890% CI: [0.93, 1.13]Mixed model with repeated measurements
Secondary
Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%)
To evaluate the effect of MEDI6570 on left ventricular systolic function among participants with reduced ejection fraction (defined as \<50%) compared with placebo
Time frame: From baseline to Day 253
Population: Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MEDI6570 50 mg | Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | -0.39 Percentage of GLS | Standard Error 1.03 |
| MEDI6570 150 mg | Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | -1.16 Percentage of GLS | Standard Error 0.78 |
| MEDI6570 400 mg | Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | 0.41 Percentage of GLS | Standard Error 0.64 |
| MEDI6570 150 mg or 400 mg | Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | -0.19 Percentage of GLS | Standard Error 0.55 |
| Placebo | Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | 1.76 Percentage of GLS | Standard Error 0.66 |
p-value: 0.95990% CI: [-4.16, -0.12]ANCOVA
p-value: 0.99890% CI: [-4.53, -1.31]ANCOVA
p-value: 0.93990% CI: [-2.79, 0.09]ANCOVA
p-value: 0.99190% CI: [-3.27, -0.62]ANCOVA
Secondary
Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%)
To evaluate the effect of MEDI6570 on left ventricular systolic function among participants with reduced ejection fraction (defined as \<50%) compared with placebo
Time frame: From baseline to Day 253
Population: Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MEDI6570 50 mg | Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | -1.08 Percentage of LVEF | Standard Error 1.52 |
| MEDI6570 150 mg | Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | 1.32 Percentage of LVEF | Standard Error 1.13 |
| MEDI6570 400 mg | Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | 2.09 Percentage of LVEF | Standard Error 1 |
| MEDI6570 150 mg or 400 mg | Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | 1.79 Percentage of LVEF | Standard Error 0.82 |
| Placebo | Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%) | 2.41 Percentage of LVEF | Standard Error 1.04 |
p-value: 0.97290% CI: [-6.49, -0.5]ANCOVA
p-value: 0.77790% CI: [-3.49, 1.3]ANCOVA
p-value: 0.59690% CI: [-2.54, 1.89]ANCOVA
p-value: 0.69890% CI: [-2.64, 1.38]ANCOVA
Secondary
Number of Participants With Adverse Events in Any Category
To assess the safety and tolerability of MEDI6570 compared with placebo
Time frame: During study follow-up (from day 1 to day 325)
Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI6570 50 mg | Number of Participants With Adverse Events in Any Category | Any AE leading to treatment discontinuation | 1 Participants |
| MEDI6570 50 mg | Number of Participants With Adverse Events in Any Category | Any AEs | 26 Participants |
| MEDI6570 50 mg | Number of Participants With Adverse Events in Any Category | Any AE leading to withdrawal from study | 0 Participants |
| MEDI6570 50 mg | Number of Participants With Adverse Events in Any Category | Any AEs with outcome of death | 0 Participants |
| MEDI6570 50 mg | Number of Participants With Adverse Events in Any Category | Any SAE (including events with outcome of death) | 4 Participants |
| MEDI6570 150 mg | Number of Participants With Adverse Events in Any Category | Any AE leading to treatment discontinuation | 0 Participants |
| MEDI6570 150 mg | Number of Participants With Adverse Events in Any Category | Any SAE (including events with outcome of death) | 17 Participants |
| MEDI6570 150 mg | Number of Participants With Adverse Events in Any Category | Any AEs with outcome of death | 1 Participants |
| MEDI6570 150 mg | Number of Participants With Adverse Events in Any Category | Any AE leading to withdrawal from study | 0 Participants |
| MEDI6570 150 mg | Number of Participants With Adverse Events in Any Category | Any AEs | 87 Participants |
| MEDI6570 400 mg | Number of Participants With Adverse Events in Any Category | Any SAE (including events with outcome of death) | 10 Participants |
| MEDI6570 400 mg | Number of Participants With Adverse Events in Any Category | Any AEs | 79 Participants |
| MEDI6570 400 mg | Number of Participants With Adverse Events in Any Category | Any AEs with outcome of death | 1 Participants |
| MEDI6570 400 mg | Number of Participants With Adverse Events in Any Category | Any AE leading to treatment discontinuation | 2 Participants |
| MEDI6570 400 mg | Number of Participants With Adverse Events in Any Category | Any AE leading to withdrawal from study | 0 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Adverse Events in Any Category | Any AE leading to withdrawal from study | 0 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Adverse Events in Any Category | Any AEs | 192 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Adverse Events in Any Category | Any AE leading to treatment discontinuation | 3 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Adverse Events in Any Category | Any SAE (including events with outcome of death) | 31 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Adverse Events in Any Category | Any AEs with outcome of death | 2 Participants |
| Placebo | Number of Participants With Adverse Events in Any Category | Any SAE (including events with outcome of death) | 13 Participants |
| Placebo | Number of Participants With Adverse Events in Any Category | Any AE leading to treatment discontinuation | 3 Participants |
| Placebo | Number of Participants With Adverse Events in Any Category | Any AEs | 65 Participants |
| Placebo | Number of Participants With Adverse Events in Any Category | Any AE leading to withdrawal from study | 0 Participants |
| Placebo | Number of Participants With Adverse Events in Any Category | Any AEs with outcome of death | 0 Participants |
Secondary
Number of Participants With Most Common Adverse Events (Frequency > 5%)
To assess the safety and tolerability of MEDI6570 compared with placebo
Time frame: During study follow-up (from day 1 to day 325)
Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pyrexia | 2 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Influenza | 2 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Non-cardiac chest pain | 3 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Nausea | 2 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pain in extremity | 2 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypertension | 2 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Epistaxis | 2 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Dyspnoea | 2 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Participants with any AE | 16 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | COVID-19 | 3 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Angina pectoris | 2 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Diarrhoea | 2 Participants |
| MEDI6570 50 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypotension | 2 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Influenza | 4 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | COVID-19 | 8 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pyrexia | 1 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Angina pectoris | 10 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Participants with any AE | 35 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Nausea | 1 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypertension | 4 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pain in extremity | 1 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypotension | 1 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Non-cardiac chest pain | 5 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Epistaxis | 1 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Dyspnoea | 3 Participants |
| MEDI6570 150 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Diarrhoea | 5 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Angina pectoris | 3 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Participants with any AE | 38 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | COVID-19 | 17 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypertension | 9 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Non-cardiac chest pain | 6 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Dyspnoea | 4 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypotension | 4 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pyrexia | 3 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Diarrhoea | 2 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Epistaxis | 2 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Influenza | 2 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Nausea | 1 Participants |
| MEDI6570 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pain in extremity | 1 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Non-cardiac chest pain | 14 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Influenza | 8 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Participants with any AE | 89 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Epistaxis | 5 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | COVID-19 | 28 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pain in extremity | 4 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Nausea | 4 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Angina pectoris | 15 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Dyspnoea | 9 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Diarrhoea | 9 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypotension | 7 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypertension | 15 Participants |
| MEDI6570 150 mg or 400 mg | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pyrexia | 6 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pain in extremity | 1 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Dyspnoea | 3 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Participants with any AE | 26 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Diarrhoea | 4 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Non-cardiac chest pain | 4 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Epistaxis | 1 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypertension | 9 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Pyrexia | 1 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Influenza | 1 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | COVID-19 | 6 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Angina pectoris | 6 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Hypotension | 1 Participants |
| Placebo | Number of Participants With Most Common Adverse Events (Frequency > 5%) | Nausea | 1 Participants |
Secondary
Summary of ADA (Anti-drug Antibody) Responses During the Study
To evaluate the immunogenicity of MEDI6570
Time frame: From baseline to Day 325/405. Day 325/405: for participants who completed the study under clinical study protocol (CSP) Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.
Population: Subjects included in the As-treated Population who have ≥ 1 immunogenicity sample will be included in the Immunogenicity Population. Subjects will be analysed according to the actual treatment they received. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI6570 50 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-boosted ADA (anti-drug antibody) positive | 0 Participants |
| MEDI6570 50 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) incidence (TEADA positive) | 2 Participants |
| MEDI6570 50 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) prevalence (positive at baseline or post-baseline) | 2 Participants |
| MEDI6570 50 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) persistently positive | 2 Participants |
| MEDI6570 50 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-induced ADA (anti-drug antibody) positive | 2 Participants |
| MEDI6570 150 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) incidence (TEADA positive) | 9 Participants |
| MEDI6570 150 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-boosted ADA (anti-drug antibody) positive | 1 Participants |
| MEDI6570 150 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) prevalence (positive at baseline or post-baseline) | 10 Participants |
| MEDI6570 150 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) persistently positive | 7 Participants |
| MEDI6570 150 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-induced ADA (anti-drug antibody) positive | 9 Participants |
| MEDI6570 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) incidence (TEADA positive) | 2 Participants |
| MEDI6570 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-boosted ADA (anti-drug antibody) positive | 0 Participants |
| MEDI6570 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) persistently positive | 1 Participants |
| MEDI6570 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-induced ADA (anti-drug antibody) positive | 2 Participants |
| MEDI6570 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) prevalence (positive at baseline or post-baseline) | 3 Participants |
| MEDI6570 150 mg or 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-induced ADA (anti-drug antibody) positive | 13 Participants |
| MEDI6570 150 mg or 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) prevalence (positive at baseline or post-baseline) | 15 Participants |
| MEDI6570 150 mg or 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) incidence (TEADA positive) | 13 Participants |
| MEDI6570 150 mg or 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-boosted ADA (anti-drug antibody) positive | 1 Participants |
| MEDI6570 150 mg or 400 mg | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) persistently positive | 10 Participants |
| Placebo | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-boosted ADA (anti-drug antibody) positive | 0 Participants |
| Placebo | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) prevalence (positive at baseline or post-baseline) | 1 Participants |
| Placebo | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) persistently positive | 1 Participants |
| Placebo | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) incidence (TEADA positive) | 1 Participants |
| Placebo | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-induced ADA (anti-drug antibody) positive | 1 Participants |
| Total | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) prevalence (positive at baseline or post-baseline) | 16 Participants |
| Total | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-boosted ADA (anti-drug antibody) positive | 1 Participants |
| Total | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) incidence (TEADA positive) | 14 Participants |
| Total | Summary of ADA (Anti-drug Antibody) Responses During the Study | ADA (anti-drug antibody) persistently positive | 11 Participants |
| Total | Summary of ADA (Anti-drug Antibody) Responses During the Study | Treatment-induced ADA (anti-drug antibody) positive | 14 Participants |
Secondary
Summary of Serum Concentrations (ug/mL) of MEDI6570
MEDI6570 concentrations as measured in serum during the intervention and follow-up periods
Time frame: From baseline to Day 325/Day 405
Population: All subjects who received ≥ 1 dose of MEDI6570 and have ≥ 1 one post dose evaluable MEDI6570 serum concentration will be included in the PK population. Subjects will be analysed according to the actual treatment they received. The pk data was analysed only for 50 mg, 150mg and 400mg groups.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Baseline | NA ug/mL | — |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 10 | 2.3126 ug/mL | Geometric Coefficient of Variation 101.5 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 29 | 0.6154 ug/mL | Geometric Coefficient of Variation 170.7 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 57 | 0.7622 ug/mL | Geometric Coefficient of Variation 235.5 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 85 | 1.1353 ug/mL | Geometric Coefficient of Variation 217.3 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 113 | 1.0084 ug/mL | Geometric Coefficient of Variation 176.7 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 122 | 4.6703 ug/mL | Geometric Coefficient of Variation 37 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 141 | 1.4191 ug/mL | Geometric Coefficient of Variation 129.5 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 169 | 0.8016 ug/mL | Geometric Coefficient of Variation 171.6 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 225 | 2.2469 ug/mL | Geometric Coefficient of Variation 86.3 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 253 | 0.7253 ug/mL | Geometric Coefficient of Variation 288.4 |
| MEDI6570 50 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 325/Day 405 | NA ug/mL | — |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 85 | 6.4317 ug/mL | Geometric Coefficient of Variation 62 |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Baseline | NA ug/mL | — |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 325/Day 405 | NA ug/mL | — |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 169 | 5.2865 ug/mL | Geometric Coefficient of Variation 163.4 |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 10 | 7.0296 ug/mL | Geometric Coefficient of Variation 125.9 |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 122 | 8.1229 ug/mL | Geometric Coefficient of Variation 792 |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 225 | 3.6384 ug/mL | Geometric Coefficient of Variation 633.4 |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 29 | 3.4641 ug/mL | Geometric Coefficient of Variation 103.2 |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 253 | 5.6832 ug/mL | Geometric Coefficient of Variation 136 |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 141 | 8.0736 ug/mL | Geometric Coefficient of Variation 47.2 |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 57 | 4.3897 ug/mL | Geometric Coefficient of Variation 145.9 |
| MEDI6570 150 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 113 | 5.4403 ug/mL | Geometric Coefficient of Variation 120.1 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 57 | 15.0108 ug/mL | Geometric Coefficient of Variation 50.3 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 85 | 10.8714 ug/mL | Geometric Coefficient of Variation 608.2 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 113 | 15.5611 ug/mL | Geometric Coefficient of Variation 77.1 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 122 | 28.1805 ug/mL | Geometric Coefficient of Variation 168.8 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 141 | 10.4080 ug/mL | Geometric Coefficient of Variation 647.5 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 253 | 14.9944 ug/mL | Geometric Coefficient of Variation 173.4 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Baseline | NA ug/mL | — |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 10 | 20.4472 ug/mL | Geometric Coefficient of Variation 37.2 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 169 | 15.9449 ug/mL | Geometric Coefficient of Variation 145.9 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 29 | 9.5328 ug/mL | Geometric Coefficient of Variation 115.4 |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 197 | NA ug/mL | — |
| MEDI6570 400 mg | Summary of Serum Concentrations (ug/mL) of MEDI6570 | Day 325/Day 405 | 0.5955 ug/mL | Geometric Coefficient of Variation 720.6 |
Secondary
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time
To assess the safety and tolerability of MEDI6570 compared with placebo
Time frame: From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.
Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 225 | 0.9 beats/min | Standard Deviation 10 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 325/405 | 0.5 beats/min | Standard Deviation 10.4 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 169 | 0.7 beats/min | Standard Deviation 10.1 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 10 | 0.4 beats/min | Standard Deviation 9.4 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 197 | 2.1 beats/min | Standard Deviation 12.5 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 57 | -2.1 beats/min | Standard Deviation 11 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 85 | -3.3 beats/min | Standard Deviation 9.4 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 29 | -0.5 beats/min | Standard Deviation 11.4 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 253 | -0.8 beats/min | Standard Deviation 12.2 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 113 | -1.8 beats/min | Standard Deviation 9.8 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 122 | -3.3 beats/min | Standard Deviation 10.8 |
| MEDI6570 50 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 141 | -1.3 beats/min | Standard Deviation 10.4 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 29 | 0.7 beats/min | Standard Deviation 8.3 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 141 | 0.8 beats/min | Standard Deviation 9.2 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 85 | 1.0 beats/min | Standard Deviation 9.2 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 197 | 2.3 beats/min | Standard Deviation 9.8 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 225 | 1.2 beats/min | Standard Deviation 11 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 169 | 0.5 beats/min | Standard Deviation 11 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 10 | 0.6 beats/min | Standard Deviation 8 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 122 | -1.2 beats/min | Standard Deviation 13.4 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 113 | 0.5 beats/min | Standard Deviation 10.1 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 57 | 0.9 beats/min | Standard Deviation 8.9 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 325/405 | 1.3 beats/min | Standard Deviation 9.8 |
| MEDI6570 150 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 253 | 0.2 beats/min | Standard Deviation 11 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 169 | 3.0 beats/min | Standard Deviation 8.8 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 10 | 0.4 beats/min | Standard Deviation 6.9 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 29 | 1.3 beats/min | Standard Deviation 8.2 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 57 | 2.5 beats/min | Standard Deviation 9.7 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 85 | 2.3 beats/min | Standard Deviation 8.3 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 113 | 0.2 beats/min | Standard Deviation 8.7 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 122 | -1.3 beats/min | Standard Deviation 7.6 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 141 | 2.0 beats/min | Standard Deviation 9.4 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 197 | 1.7 beats/min | Standard Deviation 9.5 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 225 | 2.5 beats/min | Standard Deviation 10.1 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 253 | 2.1 beats/min | Standard Deviation 10 |
| MEDI6570 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 325/405 | 1.9 beats/min | Standard Deviation 9.4 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 122 | 0.7 beats/min | Standard Deviation 16 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 113 | 0.2 beats/min | Standard Deviation 10.7 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 10 | -0.6 beats/min | Standard Deviation 8.6 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 225 | 1.8 beats/min | Standard Deviation 10.4 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 85 | 1.3 beats/min | Standard Deviation 10.4 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 57 | 1.1 beats/min | Standard Deviation 11.1 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 325/405 | 0.7 beats/min | Standard Deviation 9.9 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 253 | 0.4 beats/min | Standard Deviation 9.4 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 169 | 1.5 beats/min | Standard Deviation 9.7 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 141 | 2.2 beats/min | Standard Deviation 10.4 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 29 | -1.1 beats/min | Standard Deviation 8.5 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Heart Rate From Baseline) Variables Over Time | Heart rate Day 197 | 1.8 beats/min | Standard Deviation 10.4 |
Secondary
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time
To assess the safety and tolerability of MEDI6570 compared with placebo
Time frame: From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.
Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 141 | 0.7 mmHg | Standard Deviation 15 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 29 | -0.7 mmHg | Standard Deviation 10.8 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 57 | 1.4 mmHg | Standard Deviation 11.6 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 85 | 0.7 mmHg | Standard Deviation 10.2 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 113 | -0.6 mmHg | Standard Deviation 10.6 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 122 | 1.6 mmHg | Standard Deviation 16.4 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 10 | 0.3 mmHg | Standard Deviation 9.9 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 169 | 1.2 mmHg | Standard Deviation 13.4 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 197 | 0.7 mmHg | Standard Deviation 15.8 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 225 | 2.8 mmHg | Standard Deviation 14.3 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 253 | -1.8 mmHg | Standard Deviation 15.5 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 325/405 | -1.8 mmHg | Standard Deviation 12.8 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 10 | -0.2 mmHg | Standard Deviation 6 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 29 | 0.3 mmHg | Standard Deviation 8.5 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 57 | -1.1 mmHg | Standard Deviation 8.5 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 85 | -0.1 mmHg | Standard Deviation 9 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 113 | -0.3 mmHg | Standard Deviation 8.5 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 122 | -3.7 mmHg | Standard Deviation 10.4 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 141 | -1.5 mmHg | Standard Deviation 8.4 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 169 | -0.4 mmHg | Standard Deviation 9.5 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 197 | -1.6 mmHg | Standard Deviation 7.7 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 225 | 0.4 mmHg | Standard Deviation 9.5 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 253 | -3.7 mmHg | Standard Deviation 7.9 |
| MEDI6570 50 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 325/405 | -1.8 mmHg | Standard Deviation 8.5 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 325/405 | -0.5 mmHg | Standard Deviation 9.1 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 10 | 0.6 mmHg | Standard Deviation 8.5 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 85 | 1.5 mmHg | Standard Deviation 13.8 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 253 | -0.1 mmHg | Standard Deviation 10.7 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 225 | -1.6 mmHg | Standard Deviation 9.8 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 29 | -1.3 mmHg | Standard Deviation 8.7 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 197 | 0.6 mmHg | Standard Deviation 14 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 113 | 0.1 mmHg | Standard Deviation 9.4 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 122 | -4.0 mmHg | Standard Deviation 15.5 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 57 | -0.5 mmHg | Standard Deviation 8.4 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 57 | 0.7 mmHg | Standard Deviation 14.1 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 85 | -0.5 mmHg | Standard Deviation 10.5 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 197 | 0.0 mmHg | Standard Deviation 9.5 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 225 | 1.7 mmHg | Standard Deviation 14.8 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 169 | -0.3 mmHg | Standard Deviation 9.2 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 29 | -1.1 mmHg | Standard Deviation 14.6 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 169 | 1.5 mmHg | Standard Deviation 12.5 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 253 | 0.7 mmHg | Standard Deviation 14.4 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 141 | -0.2 mmHg | Standard Deviation 14.1 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 141 | -1.1 mmHg | Standard Deviation 9.6 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 10 | 0.9 mmHg | Standard Deviation 12.7 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 325/405 | 0.7 mmHg | Standard Deviation 14.1 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 113 | 1.3 mmHg | Standard Deviation 15.2 |
| MEDI6570 150 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 122 | -3.9 mmHg | Standard Deviation 8 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 253 | -0.9 mmHg | Standard Deviation 15.6 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 141 | -0.2 mmHg | Standard Deviation 14.1 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 169 | -0.3 mmHg | Standard Deviation 14.9 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 197 | -3.6 mmHg | Standard Deviation 13.5 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 225 | -0.6 mmHg | Standard Deviation 15.1 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 197 | -2.0 mmHg | Standard Deviation 9.8 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 169 | -0.8 mmHg | Standard Deviation 9 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 325/405 | -2.5 mmHg | Standard Deviation 14.7 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 10 | -0.3 mmHg | Standard Deviation 8.4 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 29 | -1.1 mmHg | Standard Deviation 9.7 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 225 | -0.9 mmHg | Standard Deviation 8.8 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 57 | -0.9 mmHg | Standard Deviation 8.9 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 85 | -0.9 mmHg | Standard Deviation 8.9 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 325/405 | -1.5 mmHg | Standard Deviation 10.3 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 113 | -0.5 mmHg | Standard Deviation 8.9 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 122 | -2.0 mmHg | Standard Deviation 7.5 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 253 | -1.0 mmHg | Standard Deviation 9.9 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 10 | -1.4 mmHg | Standard Deviation 13 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 29 | -1.5 mmHg | Standard Deviation 11.9 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 141 | -0.3 mmHg | Standard Deviation 8.5 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 57 | -1.6 mmHg | Standard Deviation 12.3 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 85 | -1.2 mmHg | Standard Deviation 12.7 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 113 | 0.2 mmHg | Standard Deviation 13.7 |
| MEDI6570 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 122 | -2.0 mmHg | Standard Deviation 13.8 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 253 | -0.4 mmHg | Standard Deviation 9.3 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 197 | -0.3 mmHg | Standard Deviation 9 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 169 | 0.5 mmHg | Standard Deviation 14.5 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 10 | 0.4 mmHg | Standard Deviation 12.8 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 253 | 0.2 mmHg | Standard Deviation 14.5 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 225 | -0.3 mmHg | Standard Deviation 14.7 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 122 | 7.8 mmHg | Standard Deviation 17.1 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 29 | -1.3 mmHg | Standard Deviation 12.6 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 113 | 0.6 mmHg | Standard Deviation 13.1 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 197 | -0.4 mmHg | Standard Deviation 13.6 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 169 | -0.4 mmHg | Standard Deviation 9.2 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 57 | -0.1 mmHg | Standard Deviation 12.8 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 225 | -0.8 mmHg | Standard Deviation 8.4 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 57 | -0.4 mmHg | Standard Deviation 8.5 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 141 | 0.2 mmHg | Standard Deviation 7.9 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 85 | -0.6 mmHg | Standard Deviation 9.2 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 325/405 | -0.7 mmHg | Standard Deviation 9.8 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 29 | -1.3 mmHg | Standard Deviation 9.1 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 141 | 0.8 mmHg | Standard Deviation 13.3 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 113 | 1.0 mmHg | Standard Deviation 9.1 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 10 | -0.4 mmHg | Standard Deviation 8.7 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 325/405 | 0.1 mmHg | Standard Deviation 16 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Systolic blood pressure Day 85 | -0.5 mmHg | Standard Deviation 14.9 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time | Diastolic blood pressure Day 122 | 4.1 mmHg | Standard Deviation 12.3 |
Secondary
Vital Signs (Change of Weight From Baseline to Day 325/405 )
To assess the safety and tolerability of MEDI6570 compared with placebo
Time frame: From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively
Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI6570 50 mg | Vital Signs (Change of Weight From Baseline to Day 325/405 ) | 0.316 kg | Standard Deviation 4.55 |
| MEDI6570 150 mg | Vital Signs (Change of Weight From Baseline to Day 325/405 ) | 1.445 kg | Standard Deviation 4.863 |
| MEDI6570 400 mg | Vital Signs (Change of Weight From Baseline to Day 325/405 ) | 1.078 kg | Standard Deviation 4.714 |
| MEDI6570 150 mg or 400 mg | Vital Signs (Change of Weight From Baseline to Day 325/405 ) | 0.786 kg | Standard Deviation 5.348 |