Secondary endpoints. Secondary safety endpoints include: · change from baseline in LV dimensions (end-systolic volume index, end-diastolic volume index, left ventricular mass) · change from baseline in regional (infarct related) and global wall motion score · change from baseline in ejection fraction · cardiac rupture · NT-proBNP 4 Investigational Plan
Secondary endpoints. PHARMACOKINETIC ENDPOINTS • Plasma concentrations of AT-281 (and metabolites AT-551, AT-229, AT-219, and AT- 273) for each cohort at the following timepoints: o Day 1: Pre-dose (before the first dose, time 0) o 24 hours after Dose 1 (before Dose 4 for TID dosing and before Dose 3 for BID dosing) o A day of intensive PK sampling:
Secondary endpoints. SAFETY ENDPOINTS Incidence and grade of any TEAEs from first dose through Day 28 or withdrawal from the study Incidence and grade of any SAEs through Day 28 or withdrawal from the study Vital sign measurements Physical examination findings Clinical laboratory (serum chemistry, hematology, coagulation, and urinalysis findings) ECG findings
Secondary endpoints. 9.2.2.1 Time from randomization to treatment failure defined as virologic failure (see Section 9.2.1), death, or permanent discontinuation of the NNRTI or PI components of the randomized treatment, whichever occurs first. Changes in the NRTI drugs will not constitute treatment failure. Drug-resistant plasma virus as determined at virologic failure by bulk sequencing.
Secondary endpoints. Adverse events, blood pressure (BP), heart rate (HR), and routine clinical safety laboratory testing including blood chemistry, hematology, and urine output • Change in MAP from baseline to 24 hours • Change in concentration of serum lactate from baseline to 2 hours and to 24 hours • Change in PELOD score from Screening to 24 hours
Secondary endpoints. IRRC-assessed XXX and PFS, and OS, in any-risk subjects with previously untreated RCC. Incidence of AEs in all treated subjects with previously untreated advanced or metastatic RCC Exploratory Endpoints: Overall safety and tolerability of NIVO+IPI versus sunitinib. IRRC-assessed XXX and PFS, and OS in favourable-risk subjects with previously untreated advanced or metastatic RCC. Explore potential predictive biomarkers of clinical response by analyzing tumor specimens and blood samples for proteins and genes involved in regulating immune responses. Evaluate HRQoL as assessed by FACT-G. Assess disease related symptoms in each arm based on NCCN FKSI-19. Assess changes in global health status based on EuroQol’s EQ-5D. Abbreviations: AE: adverse event; EQ-5D: EuroQoL 5-Dimensions; FACT-G: Functional Assessment of Cancer Therapy-General; FKSI-19: Functional Assessment of Cancer Therapy-Kidney Symptom Index; HRQoL: health- related quality of life; IRRC: Independent radiological review committee; IV: intravenous; NCCN; National Comprehensive Cancer Network: NIVO+IPI; nivolumab plus ipilimumab; XXX: Overall Response Rate, OS: Overall Survival, PFS: Progression free survival, Q2W: every 2 weeks, Q3W: every 3 weeks, RCC: renal cell carcinoma.
Secondary endpoints. Length of stay o Aim: Decrease length of hospital stay o Measured: Time (Hours) • Length of time for initial image processing o Aim: Decrease disturbance to surgeon workflow o Measured: Time (Minutes) • Length of time to place all screws o Aim: Reduce the time for screw placement o Measured: Time (Minutes) • Length of time to confirm screw placement o Aim: Reduce the time needed for confirmation of screw location o Measured: Time (Minutes) • Length of time to register images o Aim: To reduce time for registration of reference images o Measured: Time (Seconds) • Estimated Blood Loss (EBL) o Aim: To reduce the EBL of each case o Measured: Milliliters (mL) • Incidence of Malalignment o Aim: To decrease the incidence of pedicle screw malalignment o Measured: Misalignment angle between pilot hole and screw trajectory (degrees) • Complications: Neurological Deficits, Dural Tears, deep wound infections, etc o Aim: To decrease the incidence of intraoperative complications o Measured: number of reported complications while hospitalized • Measurement of 2D fluoroscopy radiation exposure o Aim: to reduce patient and surgeon exposure to radiation o Measured: Exposure measured by Dose Area Product (DAP)
Secondary endpoints. Structural changes of PED on OCT-Angiography Mean change in visual acuity at weeks 12, 24 and 52 compared to the baseline. Proportion of patients who gain 5, 10 and 15 letters at weeks 12, 24 and 52 Mean change in central foveal thickness and volume measured by SD-OCT at weeks 12, 24 and 52 compared to the baseline. Mean change in PED height at weeks 24 and 52 compared to the baseline. Proportion of patients with resolution of PED at weeks 24 and 52. Mean number of injections over 52 weeks. Proportion of patients with development of macular atrophy at week 52. The change of retinal function measured by Macular Integrity Assessment (MAIA) at weeks 24 and 52 compared to the baseline. Mean change in National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) score between baseline and weeks 24 and 52.
Secondary endpoints. Symptoms (angina score, NYHA class) within 1 year • Death, myocardial infarction and repeat revascularisation as individual components of XXXX • Cost-effectiveness of an MR vs FFR guided selection for revascularisation • Occurrence of new myocardial scar tissue • Ischaemia reduction in the FFR vs MR group after therapy Table 3.4: Detailed definition of end-points End Point Definition Death All cause mortality Myocardial Spontaneous Elevation of CK or Troponin Infarction above baseline with symptoms of ischaemia, ECG changes or imaging evidence of loss of myocardium(123) Peri- procedural CKMB>3X ULN- upper limit of normal (post PCI 12-24hrs) CKMB>5X ULN (post CABG 24-72 hours) plus new Q waves or LBBB, new native vessel or graft occlusion, imaging evidence of loss of viable myocardium(123) Repeat Repeat PCI or CABG of the target revascularisation lesion performed for restenosis or other complication of the target lesion (from 5mm proximal to 5mm distal to the stent) (124)
Secondary endpoints. The secondary endpoints of the study are to compare the following between the two treatment groups: • Safety as measured by adverse events, including clinically significant changes in physical examination, peripheral blood hematology, serum chemistry, urinalysis, and ECG. • The OS of patients with recurrent or metastatic SCCHN. • The ORR, DOBR, DCR, and DDC of patients with recurrent or metastatic SCCHN using irRECIST evaluated by independent radiology review.
