Study investigators of THOMAS-1 (T-1), THOMAS-2 (T-2), or both (T-1 & T-2)

Transcription

1 Appendix Study investigatrs f THOMAS-1 (T-1), THOMAS-2 (T-2), r bth (T-1 & T-2) R. Weiss (T-1 & principal investigatr fr T-2), C. Recknr (principal investigatr fr T-2), S. Arnff (T-1 & T-2), V. Awasty (T-1 & T-2), F. Bacha (T-2), B. Bhagwat (T-1), T. Blevins (T-2), R. Cllette (T-2), R. Detweiller (T-1 & T-2), A. Dwell (T-1 & T-2), P. Dzngwki (T-1 & T-2), J. Fialkw (T-1), F. Gerge (T-2), A. Gupta (T-1 & T-2), T. Hack (T-2), E. Hage-Krban (T-1 & T-2), K. Heatn (T-1), S. Kanani (T-1), A. Kivitz (T- 1 & T-2), I. Lh (T-1), M. Malne (T-1 & T-2), J. Neutel (T-2), M. O Mahny (T-2), S. Prmislff (T-1), T. Raf (T-1), A. Reichman (T-1), T. Repas (T-1), E. Riffer (T-2), H. Rseman (T-2), A. Steinberg (T-1 & T-2), J.C. Stringer (T-1 & T-2), M. Thrne (T-1)

2 Training checklists used by sites in the THOMAS studies The fllwing steps were given in bth studies regardless f the study device: Befre the training Wait 30 t 45 minutes t allw the prefilled autinjectr(s) t naturally reach rm temperature Gather all materials needed fr injectin (study device, alchl swabs, cttn ball r gauze pad, adhesive bandage, cntainer, Subject Starter Kit, 2 training units, reset tl) Inspect the study device Prepare fr injectin Explain the purpse f the training (ensure patient is cmfrtable with selfinjectin) Review study device instructins fr use Injectin instructin Chse and clean injectin site Create a firm surface n injectin site Inject evlcumab (see list belw) After the injectin Save used autinjectr and its riginal packaging r dispse f syringe in sharps cntainer Examine the injectin site

3 The fllwing steps were given fr injectin fr particular study devices: Autinjectr When ready, pull the white needle cap straight ff Place prefilled autinjectr n injectin site Push the prefilled autinjectr firmly n skin at injectin site Press the blue start buttn and release thumb Cunt slwly t 15 secnds fr injectin t finish Prefilled syringe When ready, pull the gray needle cver straight ff Remve the air bubble/air gap Hlding the pinched skin, insert the needle int the skin using 45 t 90 degree angle With slw, cnstant pressure, push plunger all the way dwn until injectin is cmplete Lift syringe gently frm skin Autmated minidser (AMD) Clean the bttm f prefilled cartridge Lad cleaned cartridge int 3.5 ml AMD Keeping the stretch, place laded injectr nt skin with blue flashing light up, and secure adhesive Press and release the start buttn Carefully peel used injectr ff skin and check study drug windw

4 Supplemental Table Supplemental Table 1. PK/PD analysis f unbund evlcumab serum cncentratin and PCSK9 levels THOMAS-1 (140 mg biweekly) Autinjectr (n = 74) PFS (n = 75) Unbund evlcumab serum cncentratin (PK), mean (SD) µg/ml Week (4.62) 3.12 (3.24) PCSK9 levels (PD), mean (SD) ng/ml Baseline (117.5) (100.9) Week (90.3) (100.9) THOMAS-2 (420 mg mnthly) Autinjectr (n = 82) AMD (n = 82) Unbund evlcumab serum cncentratin (PK), mean (SD) µg/ml Week (21.0) 29.1 (18.1) Week (8.8) 7.5 (6.2) PCSK9 levels (PD), mean (SD) ng/ml Baseline (96.1) (81.3) Week (65.4) 33.4 (68.3) Week (122.9) (114.8) AMD, autmated minidser; PCSK9, prprtein cnvertase subtilisin/kexin type 9; PFS, prefilled syringe; pharmackinetic/pharmacdynamic (PK/PD); SD, standard deviatin

5 Supplemental Figures Supplemental Figure 1. Diagrams f A) autinjectr, B) prefilled syringe, and C) autmated Minidser

6 Supplementary Figure 2a. THOMAS-1 Patient dispsitin. a Thugh the patient cmpleted all screening and efficacy assessments, the patient was prematurely enrlled int the extensin study befre cmpleting the week 8 fllw-up phne call fr adverse events. Enrllment Assessed fr eligibility (N = 271) Excluded (n = 122) Randmized (n = 149) Allcated t autinjectr (n = 74) Allcatin Allcated t prefilled syringe (n = 75) Discntinued study drug (n = 2) Adverse event (n = 1) Subject request (n =1) Discntinued study (n = 4) Withdrawal f cnsent (n = 2) Spnsr decisin a (n =1) Lst t fllw-up (n =1) Fllw-up Discntinued study drug (n = 2) (bth fr AE) Discntinued study (n = 1) (fr withdrawal f cnsent) Analyzed (n = 74) Analysis Analyzed (n = 75)

7 Supplementary Figure 2b. THOMAS-2 patient dispsitin Enrllment Assessed fr eligibility (N = 243) Excluded (n = 79) Randmized (n = 164) Allcated t autinjectr (n = 82) Allcatin Allcated t autmated minidser (n = 82) Discntinued study drug (n = 6) AE (n = 1) Subject request (n = 2) Lst t fllw-up (n = 3) Discntinued study (n = 5) (all lst t fllw-up) Fllw-up Discntinued study drug (n = 1) (subject request) Discntinued study (n = 2) Withdrawal f cnsent (n = 1) Lst t fllw-up (n = 1) Analyzed (n = 82) Analysis Analyzed (n = 82)