PPMI Data Overview Christopher S. Coffey The University of Iowa PPMI Investigators Meeting May 13-14, 2015 New York, NY
Source of data for this presentation: Information comes from: Tables produced for CSOC report Tables produced for monthly review by steering committee Additional data requests OVERVIEW All data comes from a data freeze based on data obtained from the LONI website on 05/01/2015. 2
ENROLLMENT GROUP Consented Enrolled Withdrawn Active Complete PD Subjects 487 423 32 391 0 Healthy Controls 241 196 18 178 0 SWEDD Subjects 83 64 7 17 40 Prodromal -yposmic 118 26 1 25 0 Prodromal-RBD 96 38 0 38 0 LRRK2 PD Cohort 82 70 0 70 0 LRRK2 UA Cohort 57 54 1 53 0 SNCA PD Cohort 8 8 0 8 0 SNCA UA Cohort 3 2 0 2 0 PD Registry 73 67 0 67 0 UA Registry 50 46 0 46 0 TOTAL 1298 994 59 895 40 3
ENROLLMENT - Prodromal 4
ENROLLMENT- Genetic Cohort 5
GENDER/AGE DISTRIBUTION Male Female P-Value LRRK2 Cohort PD Subjects Unaffected Subjects 25 (36%) 21 (39%) 45 (64%) 33 (61%) 0.02 0.10 SNCA Cohort PD Subjects Unaffected Subjects 3 (38%) 0 (0%) 5 (62%) 2 (100%) 0.48 N/A LRRK2 Registry PD Subjects Unaffected Subjects 34 (53%) 22 (49%) 30 (47%) 23 (51%) 0.62 0.88 SNCA Registry PD Subjects Unaffected Subjects 1 (33%) 0 (0%) 2 (67%) 1 (100%) 0.56 N/A 6
BASELINE CHARACT. (PRODROMAL) Hyposmic Subjects (N = 26) RBD Subjects (N = 38) Males 18 (69%) 32 (84%) Age (mean) 68 70 Education < 13 yrs 3 (12%) 14 (37%) Hispanic/Latino 2 (8%) 18 (47%) Caucasian 23 (88%) 34 (89%) Family Hx of PD - First Degree - Other - None 5 (19%) 0 (0%) 21 (81%) 3 (8%) 0 (0%) 35 (92%) 7
BASELINE CHARACT. (PRODROMAL) MDS-UPDRS Score - Total Score - Part I - Part II - Part III (Motor Exam) Hoehn & Yahr - Stage 0 - Stage 1 - Stage 2-5 Hyosmic Subjects (N = 26) 9.9 (7.5) 5.0 (3.5) 2.1 (2.4) 2.9 (3.6) 23 (88%) 2 (8%) 1 (4%) RBD Subjects (N = 38) 14.0 (7.7) 7.2 (4.0) 2.1 (2.6) 4.6 (3.8) 37 (100%) 0 (0%) 0 (0%) Modified Schwab 99.2 (3.9) 98.6 (3.3) Duration of Disease (months) NOTES: Hoehn & Yahr missing for one RBD Subject N/A N/A 8
BASELINE CHARACT. (PRODROMAL) Hyposmic Subjects (N = 26) RBD Subjects (N = 38) MOCA Total Score 27.3 (1.7) 25.4 (4.1) GDS Total Score 1.5 (1.5) 2.8 (2.6) SCOPA AUT Score 9.2 (5.0) 14.9 (8.3) STAS 54.9 (12.1) 68.8 (18.3) QUIP 0.3 (0.6) 0.5 (0.7) UPSIT Raw Score 15.4 (5.6) 18.2 (7.1) Epworth Sleep. Scale (Sleepy = 10 or above) REM Sleep Disorder (Positive = 5 or above) 2 (8%) 12 (32%) 11 (42%) 33 (87%) 9
BASELINE CHARACT. (PRODROMAL) Hyposmic Subjects (N = 26) RBD Subjects (N = 38) Caudate 2.5 (0.53) 1.9 (0.52) Putamen 1.4 (0.30) 1.1 (0.31) NOTES: For Prodromal Subjects, mean of left and right values are used for all analyses. 10
BASELINE CHARACT. (GENETIC COHORT) LRRK2 PD Subjects (N = 70) SNCA PD Subjects (N = 8) Unaffected Subjects (N = 56) Males 25 (36%) 3 (39%) 21 (38%) Age (mean) 62 50 61 Education < 13 yrs 24 (34%) 5 (63%) 22 (39%) Hispanic/Latino 28 (40%) 0 (0%) 7 (13%) Caucasian 57 (81%) 8 (100%) 52 (93%) Family Hx of PD - First Degree - Other - None - Missing 25 (36%) 8 (11%) 20 (29%) 17 (24%) 8 (100%) 0 (0%) 0 (0%) 0 (0%) 27 (48%) 4 (7%) 1 (2%) 24 (43%) 11
BASELINE CHARACT. (GENETIC COHORT) MDS-UPDRS Score - Total Score - Part I - Part II - Part III (Motor Exam) Hoehn & Yahr - Stage 0 - Stage 1 - Stage 2-5 - Missing LRRK2 PD Subjects (N = 70) 37.3 (18.8) 8.3 (5.8) 7.4 (6.4) 21.7 (10.4) 0 (0%) 11 (16%) 52 (75%) 7 (9%) SNCA PD Subjects (N = 8) 58.6 (36.4) 12.3 (8.4) 13.3 (6.3) 33.7 (24.6) 0 (0%) 1 (13%) 6 (75%) 1 (13%) Unaffected Subjects (N = 56) 6.7 (5.4) 3.6 (3.3) 0.6 (1.8) 2.5 (3.8) 47 (84%) 2 (4%) 3 (5%) 4 (7%) Modified Schwab 91.1 (9.8) 73.8 (11.9) 99.6 (1.9) Duration of Disease (months) 34 (25.3) 52 (11.3) N/A 12
BASELINE CHARACT. (GENETIC COHORT) LRRK2 PD Subjects (N = 70) SNCA PD Subjects (N = 8) Unaffected Subjects (N = 56) MOCA Total Score 26.0 (3.3) 24.1 (5.6) 26.4 (2.6) GDS Total Score 3.6 (3.3) 5.7 (3.4) 1.9 (2.2) SCOPA AUT Score 13.6 (8.8) 15.6 (12.4) 8.8 (6.8) STAS 73.6 (20.5) 91.5 (16.2) 61.8 (15.7) QUIP 0.5 (0.7) 2.0 (1.2) 0.4 (0.8) UPSIT Raw Score 24.9 (7.1) 11.3 (2.5) 32.1 (4.1) Epworth Sleep. Scale (Sleepy = 10 or above) REM Sleep Disorder (Positive = 5 or above) 19 (27%) 3 (38%) 7 (13%) 22 (31%) 7 (88%) 11 (20%) 13
BASELINE CHARACT. (GENETIC COHORT) LRRK2 PD Subjects (N = 70) SNCA PD Subjects (N = 8) Unaffected Subjects (N = 56) Contralateral Caudate 1.7 (0.57) 0.7 (0.13) 3.0 (0.66) Ipsilateral Caudate 2.0 (0.67) 0.9 (0.01) 3.0 (0.66) Contralateral Putamen 0.7 (0.29) 0.3 (0.01) 2.1 (0.55) Ipsilateral Putamen 0.8 (0.34) 0.4 (0.14) 2.1 (0.55) NOTES: For Unaffected Subjects and PD subjects with symmetrical presentation, mean of left and right values are used for all analyses. DaTSCAN at baseline missing for 45 LRRK2 PD subjects, 6 SNCA PD subjects, & 18 unaffected subjects. 14
VISIT COMPLIANCE 6 Months # Expected (% Seen) 1 Year # Expected (% Seen) 2 Year # Expected (% Seen) 3 Year # Expected (% Seen) 4 Year # Expected (% Seen) PD 414 (94%) 409 (96%) 367 (92%) 175 (89%) 35 (91%) HC 192 (95%) 189 (98%) 170 (95%) 134 (94%) 29 (83%) SWEDD 62 (89%) 62 (94%) 56 (88%) N/A N/A Hyposmic 12 (92%) 5 (100%) N/A N/A N/A RBD 23 (96%) 5 (80%) N/A N/A N/A Genetic Cohort PD Genetic Cohort UA 40 (85%) 4 (75%) N/A N/A N/A 32 (50%) 10 (80%) N/A N/A N/A 15
LUMBAR PUNCTURE COMPLETENESS Baseline # Expected (% Comp) 6 Months # Expected (% Comp) 1 Year #Expected (% Comp) 2 Year #Expected (% Comp) 3 Year #Expected (% Comp) 4 Year #Expected (% Comp) PD 423 (98%) 391 (88%) 393 (84%) 336 (82%) 155 (81%) 32 (72%) HC 196 (97%) 183 (87%) 185 (84%) 161 (80%) 126 (80%) 24 (79%) SWEDD 64 (92%) 55 (85%) 58 (83%) 49 (76%) N/A N/A Hyposmic 22 (91%) 10 (70%) 5 (60%) N/A N/A N/A RBD 37 (92%) 22 (91%) 4 (75%) N/A N/A N/A Genetic Cohort -PD 69 (90%) 3 (100%) N/A N/A N/A N/A Genetic Cohort UA 54 (93%) 8 (50%) N/A N/A N/A N/A 16
DATSCAN COMPLETENESS Baseline # Expected (% Comp) 1 Year #Expected (% Comp) 2 Year #Expected (% Comp) 4 Year #Expected (% Comp) PD 423 (99%) 394 (96%) 336 (94%) 32 (84%) HC 196 (91%) N/A N/A N/A SWEDD 64 (97%) N/A 49 (98%) N/A Hyposmic 26 (100%) 5 (100%) N/A N/A RBD 38 (100%) 4 (100%) N/A N/A Genetic Cohort PD Genetic Cohort UA 71 (89%) N/A N/A N/A 54 (93%) N/A N/A N/A 17
EARLY STUDY TERMINATIONS PD Subjects: 32 early study terminations 12 withdrew consent 10 due to other 4 travel distance 2 work/time demands 1 protocol violation 1 subject decided environment issues were cause of PD 1 patient decided to take anti-parkinsonian medication today 1 patient diagnosed with glioblastoma, investigator felt it was in patients best interest to withdraw from study 5 deaths 3 lost to follow-up 2 due to adverse event (headache, exasperation of PD symptoms) 18
EARLY STUDY TERMINATIONS Healthy Controls: 18 early study terminations 7 withdrew consent 6 due to other 2 travel distance 1 diagnosed with CIDP, does not want to continue 1 unwilling to comply with lumbar puncture 1 between baseline & v01 patient became employee at site 1 spouse too ill to continue subject participation 4 deaths 1 lost to follow-up 19
EARLY STUDY TERMINATIONS SWEDDs: 7 early study terminations 3 withdrew consent 2 due to other subject choice, health issues SWEDD subject, study ends at V06 2 lost to follow-up Prodromal: 1 early study termination Investigator decision Genetic Cohort: 1 early study termination other - meningioma 20
REPORTABLE EVENTS PD Subjects: 421 reportable events (378 subjects) 355 starting PD meds 32 early withdrawals 23 starting another study 5 deaths 2 changing diagnosis 2 SAE 21
REPORTABLE EVENTS Healthy Controls: 31 reportable events (27 subjects) 18 early withdrawals 6 change of diagnosis 4 deaths 1 each for starting another study, SAE, pregnancy SWEDD Subjects: 44 reportable events (37 subjects) 26 change of diagnosis 9 starting PD meds 7 early withdrawals 1 each for starting another study, SAE 22
REPORTABLE EVENTS Prodromal Cohort: 3 reportable events (3 subjects) 1 early termination 1 change of diagnosis 1 death Genetic Cohort: 1 reportable event Death 23
ADVERSE EVENTS PD vs HC Subjects with an AE: PD Subjects 152/423 (36%) Healthy Controls 84/196 (43%) RR = 0.84, 95% CI: (0.68, 1.03) Subjects with an LP-related AE: PD Subjects 137/423 (32%) Healthy Controls 78/196 (40%) RR = 0.81, 95% CI: (0.65, 1.01) Subjects with a DaTSCAN-related AE: PD Subjects 11/423 (3%) Healthy Controls 4/196 (2%) RR = 1.27, 95% CI: (0.41, 3.94) 24
ADVERSE EVENTS PD vs. SWEDD Subjects with an AE: PD Subjects 152/423 (36%) SWEDD Subjects 33/64 (52%) RR = 0.70, 95% CI: (0.53, 0.92) Subjects with an LP-related AE: PD Subjects 137/423 (32%) SWEDD Subjects 27/64 (42%) RR = 0.77, 95% CI: (0.56, 1.06) Subjects with a DaTSCAN-related AE: PD Subjects 11/423 (3%) SWEDD Subjects 4/64 (6%) RR = 0.42, 95% CI: (0.14, 1.28) Increased reporting of Back Pain in SWEDD group (4% vs. 11% of subjects): RR = 0.32, 95% CI: (0.14, 0.75) 25
SERIOUS ADVERSE EVENTS PD Subjects: 4 SAEs (in 4 subjects) Death Operation Due to Halux Valgus Surgery of Arthrosis Left Knee Fracture in Hip Healthy Controls: 1 SAE (in 1 subject) Tractor Accident SWEDD Subjects: 1 SAE (in 1 subject) 1 Confusional State None related to LP or DaTSCAN. 26
TIME TO START PD MEDICATIONS 27
TD/PIGD OVER TIME 381 Subjects with a Baseline & 1 Year Assessment: Of the 266 Subjects TD at Baseline: 215 (81%) also TD at 1 Year 21 (8%) Indeterminate at 1 Year 30 (11%) PIGD at 1 Year Of the 72 Subjects PIGD at Baseline: 18 (25%) TD at 1 Year 7 (10%) Indeterminate at 1 Year 47 (65%) also PIGD at 1 Year 28
MDS-UPDRS OVER TIME Report generated on data submitted as of: 13Apr2015 Baseline Month 6 Year 1 Year 2 Year 3 Year 4 PD 32 (422) (7, 72) 39 (388) (4, 94) 39 (378) (6, 113) 43 (333) (10, 96) 48 (154) (13, 121) 55 (37) (20, 100) HC 5 (195) (0, 20) 5 (185) (0, 25) 5 (162) (0, 26) 6 (127) (0, 24) 5 (22) (0, 25) SWEDD 28 (64) (4, 91) 32 (55) (4, 105) 30 (57) (3, 78) 33 (50) (3, 122) N/A N/A 29
MDS-UPDRS OVER TIME Report generated on data submitted as of: 13Apr2015 Baseline Month 6 Year 1 Year 2 Year 3 Year 4 Untreated 32 (422) (7, 72) 40 (374) (4, 94) 39 (166) (13, 113) 40 (59) (14, 76) 39 (22) (13, 74) N/A ON Scores N/A N/A 34 (134) (4, 79) 37 (169) (5, 80) 44 (74) (8, 109) 51 (23) (22, 89) OFF Scores N/A 33 (29) (11, 61) 39 (216) (6, 89) 43 (274) (10, 96) 49 (132) (13, 121) 57 (35) (24, 100) 30
MDS-UPDRS OVER TIME Analysis performed to assess change from baseline to year 1 in MDS-UPDRS Total Score (untreated or OFF). Following correlated with greater increase in year one: Lower baseline MDS-UPDRS scores Not starting ST therapy within the first year Lower contralateral putamen at baseline Higher T-Tau at baseline Lower alpha-synuclein at baseline 31
DATSCAN OVER TIME Report generated on data submitted as of: 13Apr2015 Baseline PD 0.7 (419) (0.1, 2.2) HC 2.2 (193) (0.6, 3.9) SWEDD 2.1 (62) (0.8, 3.2) Year 1 0.6 (348) (0.1, 1.8) N/A 1.8 (26) (0.8, 2.4) Year 2 0.6 (169) (0.2, 1.5) N/A N/A 32
DATSCAN OVER TIME Analysis performed to assess change from baseline to year 1 in Contralateral Putaman from DAT imaging. Following correlated with greater increase in year one: Lower baseline contralateral putamen Lower baseline SCOPA-AUT score Higher UPSIT raw score at baseline 33
SCOPA-AUT OVER TIME Report generated on data submitted as of: 13Apr2015 Baseline Month 6 Year 1 Year 2 Year 3 Year 4 PD 10 (423) (0, 39) 10 (403) (0, 40) 11 (395) (0, 45) 12 (344) (0, 42) 13 (157) (0, 31) 15 (39) (3, 34) HC 6 (195) (0, 20) N/A 6 (185) (0, 22) 6 (162) (0, 22) 7 (128) (0, 28) 6 (22) (1, 17) SWEDD 14 (64) (2, 44) 15 (55) (0, 44) 14 (58) (2, 42) 13 (51) (0, 41) N/A 34
MOCA OVER TIME Report generated on data submitted as of: 13Apr2015 Baseline Median (N) Year 1 Median (N) Year 2 Median (N) Year 3 Median (N) Year 4 Median (N) PD 27 (423) (17, 30) 26 (392) (15, 30) 26 (340) (14, 30) 26 (158) (13, 30) 26 (38) (13, 30) HC 28 (196) (26, 30) 27 (185) (20, 30) 27 (162) (21, 30) 27 (128) (19, 30) 28 (22) (24, 30) SWEDD 27 (64) (17, 30) 26 (58) (20, 30) 26 (50) (16, 30) N/A 35
ALPHA-SYNUCLEIN OVER TIME Report generated on data submitted as of: 13Apr2015 Baseline N Mean (SD) PD 412 1845 (786) HC 189 2204 (1089) SWEDD 59 2141 (1027) Month 6 N Mean (SD) 175 1882 (741) 114 2188 (917) 24 2153 (876) Year 1 N Mean (SD) 176 1872 (805) 114 2155 (956) 24 1987 (642) 36
T-TAU OVER TIME Report generated on data submitted as of: 13Apr2015 Baseline N Mean (SD) PD 408 45 (18.3) HC 187 53 (27.2) SWEDD 59 48 (23.0) Month 6 N Mean (SD) 176 42 (16.9) 114 51 (23.8) 23 53 (29.0) Year 1 N Mean (SD) 175 43 (17.4) 114 53 (27.0) 24 52 (27.4) 37
P-TAU OVER TIME Report generated on data submitted as of: 13Apr2015 Baseline N Mean (SD) Month 6 N Mean (SD) Year 1 N Mean (SD) PD 410 16 (10.1) 176 15 (9.8) 175 19 (11.7) HC 189 18 (11.7) 114 16 (8.4) 114 20 (12.6) SWEDD 59 17 (11.8) 24 20 (15.1) 24 22 (11.9) 38
A-BETA OVER TIME Report generated on data submitted as of: 13Apr2015 Baseline N Mean (SD) Month 6 N Mean (SD) Year 1 N Mean (SD) PD 412 371 (100.4) 176 364 (98.3) 176 377 (103.6) HC 189 378 (113.6) 114 373 (98.6) 114 387 (105.3) SWEDD 59 404 (106.9) 24 377 (81.0) 24 397 (75.5) 39