Trial Outcomes & Findings for Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. (NCT NCT04623242)

NCT ID: NCT04623242

Last Updated: 2022-09-22

Results Overview

Multivariate Disease Progression Model adjusted for Estimated Years to Onset (EYO)and includes all timepoints up to treatment discontinuation. The treatment effect is reported relative to the mutation positive placebo arm. Multivariate Cognitive Endpoint comprising: (i) Wechsler Memory Scale-Revised Logical Memory Delayed Recall Test (MEMUNITS), (ii) Wechsler Adult Intelligence Scale Digit Symbol Substitution Test (WAIS), (iii) Mini-Mental State Examination (MMSE), and (iv) International Shopping List Task (ISLT). Measurements for each test were normalized using the mean (SD) at DIAN-TU-001 baseline for mutation negative subjects. Higher scores indicate more favourable cognitive performance.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 194 participants
• Primary outcome timeframe: Baseline through Week 260
• Results posted on: 2022-09-22

Participant Flow

This study assigned treatment to 194 participants, 1 participant enrolled in the solanezumab arm did not receive treatment. Of the 193 participants, there were 144 mutation positive participants who were treated. Two of these participants did not have post-baseline data and were excluded from the MITT. Forty-nine mutation negative participants were enrolled across the 2 drug arms but are not part of the analysis population.

Primary analyses used a pooled control group (gantenerumab and solanezumab shared, mutation positive placebo with dynamic borrowing of DIAN-OBS data).

Participant milestones

Measure	Gantenerumab Gantenerumab: Subcutaneously every 4 weeks at escalating doses Participants randomized to gantenerumab were then randomized to either active drug or placebo at a 3:1 ratio. All mutation negative participants were assigned to placebo. For analysis purposes, mutation positive placebos were pooled for outcome measures.	Solanezumab Solanezumab: Intravenous infusion every 4 weeks at escalating doses Participants randomized to solanezumab were then randomized to either active drug or placebo at a 3:1 ratio. All mutation negative participants were assigned to placebo. For analysis purposes, mutation positive placebos were pooled for outcome measures. Some secondary measures used direct placebo as specified in the respective outcomes (those randomized to solanezumab only)	Mutation Positive Placebo Mutation positive placebos enrolled under each arm but pooled for result reporting.	Mutation Negative Placebo Mutation negative participants receiving placebo. Not analyzed as part of the Pooled Placebo Group; analyzed for safety.	DIAN-OBS Participants from the DIAN Observational study meeting specific criteria as outlined in the posted Statistical Analysis Plan.
Overall Study STARTED	52	52	40	49	69
Overall Study COMPLETED	39	36	30	26	69
Overall Study NOT COMPLETED	13	16	10	23	0

Reasons for withdrawal

Measure	Gantenerumab Gantenerumab: Subcutaneously every 4 weeks at escalating doses Participants randomized to gantenerumab were then randomized to either active drug or placebo at a 3:1 ratio. All mutation negative participants were assigned to placebo. For analysis purposes, mutation positive placebos were pooled for outcome measures.	Solanezumab Solanezumab: Intravenous infusion every 4 weeks at escalating doses Participants randomized to solanezumab were then randomized to either active drug or placebo at a 3:1 ratio. All mutation negative participants were assigned to placebo. For analysis purposes, mutation positive placebos were pooled for outcome measures. Some secondary measures used direct placebo as specified in the respective outcomes (those randomized to solanezumab only)	Mutation Positive Placebo Mutation positive placebos enrolled under each arm but pooled for result reporting.	Mutation Negative Placebo Mutation negative participants receiving placebo. Not analyzed as part of the Pooled Placebo Group; analyzed for safety.	DIAN-OBS Participants from the DIAN Observational study meeting specific criteria as outlined in the posted Statistical Analysis Plan.
Overall Study Withdrawal by Subject	7	12	5	7	0
Overall Study Reason Not Disclosed to protect treatment and genetic unblinding	6	4	5	3	0
Overall Study Subject unblinded to mutation status	0	0	0	13	0

Baseline Characteristics

Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.

Baseline characteristics by cohort

Measure	Gantenerumab n=52 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses	Solanezumab n=52 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses	Mutation Positive Placebo n=40 Participants Mutation Positive Placebos enrolled under each arm but pooled for result reporting.	Mutation Negative Placebo n=49 Participants Mutation Negative Placebos enrolled under each arm but pooled for this reporting.	DIAN-OBS Control Group n=69 Participants Data from participants in the DIAN-OBS study who met DIAN-TU inclusion criteria were used as natural history controls for improved estimates of the placebo group.	Total n=262 Participants Total of all reporting groups
Age, Continuous	46 years STANDARD_DEVIATION 10.8 • n=52 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	42.7 years STANDARD_DEVIATION 9.6 • n=50 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	44.2 years STANDARD_DEVIATION 9.6 • n=40 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	42.6 years STANDARD_DEVIATION 9.3 • n=49 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	42.3 years STANDARD_DEVIATION 9.6 • n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	43.7 years STANDARD_DEVIATION 9.9 • n=260 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Sex: Female, Male Female	21 Participants n=52 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	29 Participants n=50 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	22 Participants n=40 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	23 Participants n=49 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	47 Participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	142 Participants n=260 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Sex: Female, Male Male	31 Participants n=52 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	21 Participants n=50 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	18 Participants n=40 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	26 Participants n=49 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	22 Participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	118 Participants n=260 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=52 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	7 Participants n=50 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	5 Participants n=40 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	11 Participants n=49 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	15 Participants n=69 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	45 Participants n=260 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=52 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	43 Participants n=50 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	35 Participants n=40 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	38 Participants n=49 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	53 Participants n=69 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	214 Participants n=260 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=52 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	0 Participants n=50 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	0 Participants n=40 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	0 Participants n=49 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	1 Participants n=69 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	1 Participants n=260 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Region of Enrollment Canada	4 participants n=52 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	3 participants n=50 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	5 participants n=40 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	4 participants n=49 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	0 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	16 participants n=260 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Region of Enrollment United States	32 participants n=52 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	30 participants n=50 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	18 participants n=40 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	35 participants n=49 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	35 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	150 participants n=260 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Region of Enrollment United Kingdom	5 participants n=52 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	5 participants n=50 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	4 participants n=40 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	2 participants n=49 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	5 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	21 participants n=260 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Region of Enrollment Australia	4 participants n=52 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	6 participants n=50 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	5 participants n=40 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	1 participants n=49 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	12 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	28 participants n=260 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Region of Enrollment France	4 participants n=52 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	5 participants n=50 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	4 participants n=40 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	7 participants n=49 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	0 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	20 participants n=260 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Region of Enrollment Spain	3 participants n=52 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	1 participants n=50 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	4 participants n=40 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	0 participants n=49 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	0 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	8 participants n=260 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Region of Enrollment Argentina	—	—	—	—	4 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	4 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Region of Enrollment Japan	—	—	—	—	3 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	3 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
Region of Enrollment Germany	—	—	—	—	10 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.	10 participants n=69 Participants • Measure Analysis Population Description: Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population.
APOE4	16 Participants n=52 Participants • APOE was not included for the external DIAN-OBS Control Group because the data was not available from a CLIA certified lab	14 Participants n=50 Participants • APOE was not included for the external DIAN-OBS Control Group because the data was not available from a CLIA certified lab	13 Participants n=40 Participants • APOE was not included for the external DIAN-OBS Control Group because the data was not available from a CLIA certified lab	16 Participants n=49 Participants • APOE was not included for the external DIAN-OBS Control Group because the data was not available from a CLIA certified lab	—	59 Participants n=191 Participants • APOE was not included for the external DIAN-OBS Control Group because the data was not available from a CLIA certified lab
Enrollment EYO	-3.5 years STANDARD_DEVIATION 7.1 • n=52 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Data could not be reported for the DIAN-Obs Control group for the International Shopping List Test-Delayed Recall (ISLT) because data was not collected.	-2.4 years STANDARD_DEVIATION 7.1 • n=50 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Data could not be reported for the DIAN-Obs Control group for the International Shopping List Test-Delayed Recall (ISLT) because data was not collected.	-3.5 years STANDARD_DEVIATION 7.6 • n=40 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Data could not be reported for the DIAN-Obs Control group for the International Shopping List Test-Delayed Recall (ISLT) because data was not collected.	-4.8 years STANDARD_DEVIATION 6.41 • n=49 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Data could not be reported for the DIAN-Obs Control group for the International Shopping List Test-Delayed Recall (ISLT) because data was not collected.	—	-3.25 years STANDARD_DEVIATION 7.2 • n=191 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Data could not be reported for the DIAN-Obs Control group for the International Shopping List Test-Delayed Recall (ISLT) because data was not collected.
Digit Symbol Substitution Test	46.96 score on a scale STANDARD_DEVIATION 20.56 • n=52 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	46.06 score on a scale STANDARD_DEVIATION 19.94 • n=50 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	46.63 score on a scale STANDARD_DEVIATION 19.12 • n=40 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	60.78 score on a scale STANDARD_DEVIATION 13.01 • n=49 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	50.34 score on a scale STANDARD_DEVIATION 18.57 • n=68 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	47.76 score on a scale STANDARD_DEVIATION 19.45 • n=259 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.
MMSE	27.10 score on a scale STANDARD_DEVIATION 3.45 • n=52 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	26.72 score on a scale STANDARD_DEVIATION 4.11 • n=50 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	26.68 score on a scale STANDARD_DEVIATION 3.97 • n=40 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	29.08 score on a scale STANDARD_DEVIATION 1.17 • n=49 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	26.96 score on a scale STANDARD_DEVIATION 3.22 • n=68 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.	26.88 score on a scale STANDARD_DEVIATION 3.63 • n=259 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. DIAN Obs control group only analyzed 68 participants as one participant did not have a baseline measure.
Logical Memory Delayed Recall Test	9.9 score on a scale STANDARD_DEVIATION 6.33 • n=51 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed for this measure in the gantenerumab as 1 participant did not have a baseline measure.	9.86 score on a scale STANDARD_DEVIATION 6.86 • n=50 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed for this measure in the gantenerumab as 1 participant did not have a baseline measure.	9.4 score on a scale STANDARD_DEVIATION 6.45 • n=40 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed for this measure in the gantenerumab as 1 participant did not have a baseline measure.	14.55 score on a scale STANDARD_DEVIATION 3.72 • n=49 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed for this measure in the gantenerumab as 1 participant did not have a baseline measure.	9.32 score on a scale STANDARD_DEVIATION 6.42 • n=69 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed for this measure in the gantenerumab as 1 participant did not have a baseline measure.	9.60 score on a scale STANDARD_DEVIATION 6.47 • n=259 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed for this measure in the gantenerumab as 1 participant did not have a baseline measure.
International Shopping List Test-Delayed Recall (ISLT)	5.96 score on a scale STANDARD_DEVIATION 4.04 • n=51 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed here for gantenerumab as 1 participant did not have a baseline measure.	6.56 score on a scale STANDARD_DEVIATION 3.95 • n=50 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed here for gantenerumab as 1 participant did not have a baseline measure.	5.80 score on a scale STANDARD_DEVIATION 4.42 • n=40 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed here for gantenerumab as 1 participant did not have a baseline measure.	8.80 score on a scale STANDARD_DEVIATION 1.99 • n=49 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed here for gantenerumab as 1 participant did not have a baseline measure.	—	6.13 score on a scale STANDARD_DEVIATION 4.10 • n=190 Participants • Fifty-two participants were randomized to the solanezumab arm; two did not have post-baseline data and were excluded from the modified intent-to-treat population. Only 51 analyzed here for gantenerumab as 1 participant did not have a baseline measure.

PRIMARY outcome

Timeframe: Baseline through Week 260

Population: The endpoint itself is a ratio based on feeding z-scores for four separate parameters into a model, with programming providing the ratio under model assumptions rather than providing a treatment-specific value this is used to generate the ratio. The four individual parameters are described in other outcomes. There are no "by-arm" values for any MDPM analysis.

Multivariate Disease Progression Model adjusted for Estimated Years to Onset (EYO)and includes all timepoints up to treatment discontinuation. The treatment effect is reported relative to the mutation positive placebo arm.

Multivariate Cognitive Endpoint comprising: (i) Wechsler Memory Scale-Revised Logical Memory Delayed Recall Test (MEMUNITS), (ii) Wechsler Adult Intelligence Scale Digit Symbol Substitution Test (WAIS), (iii) Mini-Mental State Examination (MMSE), and (iv) International Shopping List Task (ISLT). Measurements for each test were normalized using the mean (SD) at DIAN-TU-001 baseline for mutation negative subjects. Higher scores indicate more favourable cognitive performance.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=161 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=160 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Assess Cognitive Efficacy in Individuals With Mutations Causing Dominantly Inherited AD as Measured by the DIAN-Multivariate Cognitive Endpoint (DIAN-MCE);	1.063 Ratio Standard Deviation 0.059	1.255 Ratio Standard Deviation 0.061

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

CDR-SB score is considered a more detailed quantitative general index of cognition and function, and provides more information than the global CDR score in patients with mild dementia

Scores range from 0-18 with lower scores showing more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=52 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Gantenerumab: Rate of Change Over Time- Clinical Dementia Rating Sum of Boxes (CDR-SB) Week 52	0.74 units on a scale Standard Error 0.202	0.44 units on a scale Standard Error 0.231
Gantenerumab: Rate of Change Over Time- Clinical Dementia Rating Sum of Boxes (CDR-SB) Week 104	1.27 units on a scale Standard Error 0.364	1.36 units on a scale Standard Error 0.414
Gantenerumab: Rate of Change Over Time- Clinical Dementia Rating Sum of Boxes (CDR-SB) Week 156	1.95 units on a scale Standard Error 0.511	2.28 units on a scale Standard Error 0.580
Gantenerumab: Rate of Change Over Time- Clinical Dementia Rating Sum of Boxes (CDR-SB) Week 208	2.96 units on a scale Standard Error 0.726	3.24 units on a scale Standard Error 0.819
Gantenerumab: Rate of Change Over Time- Clinical Dementia Rating Sum of Boxes (CDR-SB) Week 260	4.61 units on a scale Standard Error 1.220	5.76 units on a scale Standard Error 1.437

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

The Functional Assessment Scale is to be administered and completed by the study partner about subjects for whom they care. This scale measures instrumental activities of daily living such as preparing balanced meals and managing personal finances. The intent of the FAS is to assess change in an individual's functional activities, relative to previously attained abilities, that are caused by cognitive dysfunction. If the study partner indicates that the subject no longer performs a particular task, it is reasonable to probe further and ask if they think the subject could still do the task. This will help tease out the relevant cognitive impairment

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=52 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Gantenerumab: Rate of Change Over Time- Functional Assessment Scale (FAS) Week 52	1.23 units on a scale Standard Error 0.408	1.40 units on a scale Standard Error 0.469
Gantenerumab: Rate of Change Over Time- Functional Assessment Scale (FAS) Week 104	2.34 units on a scale Standard Error 0.680	2.44 units on a scale Standard Error 0.790
Gantenerumab: Rate of Change Over Time- Functional Assessment Scale (FAS) Week 156	3.45 units on a scale Standard Error 0.921	4.07 units on a scale Standard Error 1.061
Gantenerumab: Rate of Change Over Time- Functional Assessment Scale (FAS) Week 208	4.34 units on a scale Standard Error 1.202	5.55 units on a scale Standard Error 1.373
Gantenerumab: Rate of Change Over Time- Functional Assessment Scale (FAS) Week 260	6.40 units on a scale Standard Error 1.730	5.69 units on a scale Standard Error 2.073

SECONDARY outcome

Timeframe: Baseline, Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

In vivo quantification of β-amyloid deposition using positron emission tomography. This measure is a composite of brain regions. Higher scores indicate worse disease stage.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=52 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Gantenerumab: Imaging Measures Composite [11C] PiB Partial Volume Corrected Regional Spread Function Standardized Uptake Value Ratio - Composite Week 52	-0.006 Ratio Standard Error 0.0402	0.103 Ratio Standard Error 0.0454
Gantenerumab: Imaging Measures Composite [11C] PiB Partial Volume Corrected Regional Spread Function Standardized Uptake Value Ratio - Composite Week 104	-0.106 Ratio Standard Error 0.0422	0.134 Ratio Standard Error 0.0470
Gantenerumab: Imaging Measures Composite [11C] PiB Partial Volume Corrected Regional Spread Function Standardized Uptake Value Ratio - Composite Week 208	-0.334 Ratio Standard Error 0.0736	0.306 Ratio Standard Error 0.0839

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Clinical Dementia Rating - Global Score - Number of Subjects with an Increase from Baseline by Visit

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 52 · Increase from baseline CDR Global Score	11 Participants	8 Participants
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 52 · No increase from baseline CDR Global Score	38 Participants	32 Participants
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 104 · Increase from baseline CDR Global Score	18 Participants	8 Participants
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 104 · No increase from baseline CDR Global Score	29 Participants	28 Participants
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 156 · Increase from baseline CDR Global Score	16 Participants	13 Participants
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 156 · No increase from baseline CDR Global Score	26 Participants	19 Participants
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 208 · Increase from baseline CDR Global Score	12 Participants	8 Participants
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 208 · No increase from baseline CDR Global Score	24 Participants	22 Participants
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 260 · Increase from baseline CDR Global Score	5 Participants	3 Participants
Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) Week 260 · No increase from baseline CDR Global Score	8 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

CDR-SB score is considered a more detailed quantitative general index and provides more information than the global CDR score in patients with mild dementia

Scores range from 0-18 with lower scores showing more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Clinical Measures- CDR Sum of Boxes (CDR-SB) Week 52	0.90 units on a scale Standard Error 0.208	0.44 units on a scale Standard Error 0.231
Solanezumab: Clinical Measures- CDR Sum of Boxes (CDR-SB) Week 104	1.87 units on a scale Standard Error 0.367	1.36 units on a scale Standard Error 0.414
Solanezumab: Clinical Measures- CDR Sum of Boxes (CDR-SB) Week 156	2.55 units on a scale Standard Error 0.512	2.28 units on a scale Standard Error 0.580
Solanezumab: Clinical Measures- CDR Sum of Boxes (CDR-SB) Week 208	3.65 units on a scale Standard Error 0.723	3.24 units on a scale Standard Error 0.819
Solanezumab: Clinical Measures- CDR Sum of Boxes (CDR-SB) Week 260	4.87 units on a scale Standard Error 1.212	5.76 units on a scale Standard Error 1.437

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

The Geriatric Depression Scale (GDS) is a self-report measure of depression in older adults. Users respond in a "Yes/No" format. Of the 15 items, 10 indicate the presence of depression when answered positively while the other 5 are indicative of depression when answered negatively.

Scores range from 0-15 for completed questionnaires. A score of 88 is recorded for participants unable to complete the test.

Lower scores show more favorable outcome.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Clinical Measures- Geriatric Depression Scale (GDS) Week 52	0.20 score on a scale Standard Error 0.230	-0.14 score on a scale Standard Error 0.255
Solanezumab: Clinical Measures- Geriatric Depression Scale (GDS) Week 104	0.06 score on a scale Standard Error 0.265	0.03 score on a scale Standard Error 0.304
Solanezumab: Clinical Measures- Geriatric Depression Scale (GDS) Week 208	-0.12 score on a scale Standard Error 0.294	0.36 score on a scale Standard Error 0.328
Solanezumab: Clinical Measures- Geriatric Depression Scale (GDS) Week 260	-0.16 score on a scale Standard Error 0.544	0.66 score on a scale Standard Error 0.820
Solanezumab: Clinical Measures- Geriatric Depression Scale (GDS) Week 156	-0.22 score on a scale Standard Error 0.250	-0.07 score on a scale Standard Error 0.276

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

The questionnaire is to be administered and completed by the study partner about patients for whom they care. Each of the 12 NPI-Q domains contains a survey question that reflects cardinal symptoms of that domain. Initial responses to each domain question are "Yes"(present) or "No" (absent). If the response to the domain question is "No", the study partner goes to the next question. If "Yes", the study partner then rates both the Severity of the symptoms present within the last month on a 3-point scale and the associated impact of the symptom manifestations on them (i.e. Caregiver Distress) using a 5-point scale. The NPI-Q provides symptom 'Severity' and 'Distress' ratings for each symptom reported, and total 'Severity' and 'Distress' scores reflecting the sum of individual domain scores.

Scores range from 0-36 with lower scores indicating more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Clinical Measures- Neuropsychiatric Inventory Questionnaire (NPI-Q) Week 52	0.49 score on a scale Standard Error 0.416	1.06 score on a scale Standard Error 0.460
Solanezumab: Clinical Measures- Neuropsychiatric Inventory Questionnaire (NPI-Q) Week 104	0.70 score on a scale Standard Error 0.463	1.54 score on a scale Standard Error 0.530
Solanezumab: Clinical Measures- Neuropsychiatric Inventory Questionnaire (NPI-Q) Week 156	1.31 score on a scale Standard Error 0.459	1.10 score on a scale Standard Error 0.522
Solanezumab: Clinical Measures- Neuropsychiatric Inventory Questionnaire (NPI-Q) Week 260	1.83 score on a scale Standard Error 0.934	1.16 score on a scale Standard Error 1.212
Solanezumab: Clinical Measures- Neuropsychiatric Inventory Questionnaire (NPI-Q) Week 208	2.11 score on a scale Standard Error 0.575	1.74 score on a scale Standard Error 0.639

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

The Functional Assessment Scale is to be administered and completed by the study partner about subjects for whom they care. This scale measures instrumental activities of daily living such as preparing balanced meals and managing personal finances. The intent of the FAS is to assess change in an individual's functional activities, relative to previously attained abilities, that are caused by cognitive dysfunction. If the study partner indicates that the subject no longer performs a particular task, it is reasonable to probe further and ask if they think the subject could still do the task. This will help tease out the relevant cognitive impairment

Scores range from 0-30 with lower scores indicate more favorable cognitive performance

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Clinical Measures- Functional Assessment Scale (FAS) Week 52	0.68 units on a scale Standard Error 0.430	1.40 units on a scale Standard Error 0.469
Solanezumab: Clinical Measures- Functional Assessment Scale (FAS) Week 104	2.21 units on a scale Standard Error 0.690	2.44 units on a scale Standard Error 0.790
Solanezumab: Clinical Measures- Functional Assessment Scale (FAS) Week 156	3.03 units on a scale Standard Error 0.926	4.07 units on a scale Standard Error 1.061
Solanezumab: Clinical Measures- Functional Assessment Scale (FAS) Week 208	4.33 units on a scale Standard Error 1.208	5.55 units on a scale Standard Error 1.373
Solanezumab: Clinical Measures- Functional Assessment Scale (FAS) Week 260	5.82 units on a scale Standard Error 1.748	5.69 units on a scale Standard Error 2.073

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

MMSE is a brief, quantitative measure of cognitive status in adults used to screen for cognitive impairment, to estimate the severity of cognitive impairment at a given point in time, to follow the course of cognitive changes in an individual over time, and to document an individual's response to treatment.

Scores range from 0-30 and higher scores indicate more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Clinical Measures- Mini-Mental Status State Examination (MMSE) Week 52	-1.30 units on a scale Standard Error 0.354	-0.83 units on a scale Standard Error 0.391
Solanezumab: Clinical Measures- Mini-Mental Status State Examination (MMSE) Week 104	-2.59 units on a scale Standard Error 0.603	-1.73 units on a scale Standard Error 0.677
Solanezumab: Clinical Measures- Mini-Mental Status State Examination (MMSE) Week 156	-3.76 units on a scale Standard Error 0.858	-3.23 units on a scale Standard Error 0.964
Solanezumab: Clinical Measures- Mini-Mental Status State Examination (MMSE) Week 208	-5.31 units on a scale Standard Error 1.137	-4.30 units on a scale Standard Error 1.275
Solanezumab: Clinical Measures- Mini-Mental Status State Examination (MMSE) Week 260	-7.88 units on a scale Standard Error 1.799	-5.94 units on a scale Standard Error 2.143

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Classic list-learning test that measures verbal learning & memory.

Scores range from 0-12 with higher scores indicating more favorable cognitive performance.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- International Shopping List Task 30-Minute Delayed Recall Week 52	-0.35 units on a scale Standard Error 0.248	-0.17 units on a scale Standard Error 0.274
Solanezumab: Cognitive Measures- International Shopping List Task 30-Minute Delayed Recall Week 104	-0.98 units on a scale Standard Error 0.300	-0.64 units on a scale Standard Error 0.343
Solanezumab: Cognitive Measures- International Shopping List Task 30-Minute Delayed Recall Week 156	-1.55 units on a scale Standard Error 0.294	-0.42 units on a scale Standard Error 0.333
Solanezumab: Cognitive Measures- International Shopping List Task 30-Minute Delayed Recall Week 208	-1.92 units on a scale Standard Error 0.396	-0.93 units on a scale Standard Error 0.447
Solanezumab: Cognitive Measures- International Shopping List Task 30-Minute Delayed Recall Week 260	-1.45 units on a scale Standard Error 0.548	-1.86 units on a scale Standard Error 0.680

SECONDARY outcome

Timeframe: Baseline, Week 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end). Tasks are only included where assessed for subjects with a baseline Clinical Dementia Rating Global Score less than 1.

The Groton Maze Learning Test 30 minute delayed recall measures episodic memory. The primary outcome is the number of errors made during recall of the previously memorized pathway from the Groton Maze Learning Test. The minimum score is 0 errors and the max is 999. Lower scores indicate better cognitive performance.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- Groton Maze Learning Test 30 Minute Delayed Recall Week 52	1.00 count of errors Standard Error 0.975	-0.13 count of errors Standard Error 1.043
Solanezumab: Cognitive Measures- Groton Maze Learning Test 30 Minute Delayed Recall Week 104	1.16 count of errors Standard Error 1.108	0.78 count of errors Standard Error 1.207
Solanezumab: Cognitive Measures- Groton Maze Learning Test 30 Minute Delayed Recall Week 208	4.33 count of errors Standard Error 1.319	1.60 count of errors Standard Error 1.470
Solanezumab: Cognitive Measures- Groton Maze Learning Test 30 Minute Delayed Recall Week 156	2.40 count of errors Standard Error 1.055	0.96 count of errors Standard Error 1.181
Solanezumab: Cognitive Measures- Groton Maze Learning Test 30 Minute Delayed Recall Week 260	5.11 count of errors Standard Error 2.894	6.99 count of errors Standard Error 3.861

SECONDARY outcome

Timeframe: Baseline, Week 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end). Tasks are only included where assessed for subjects with a baseline Clinical Dementia Rating Global Score less than 1.

The Groton Maze Learning Test measures executive function using a maze learning paradigm. A 10 x 10 grid of tiles is presented to the participant on the screen. A 28-step pathway is hidden among these tiles. A blue tile indicates the start and a tile with red circles indicates the finish. The participant must move one step at a time from the start toward the end by touching a tile next to their current location. If the correct move is made a green checkmark appears and if the move is incorrect a red cross is revealed. Once completed, they are returned to the start location to repeat the test and must try to remember the pathway they have just completed. "Delayed Reverse Recall" measures spatial working memory.

The outcome is the number of errors made with the range of 0-999. Lower scores indicate better cognitive performance.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- Groton Maze Learning Test Delayed Reversed Recall Week 52	7.08 number of errors Standard Error 2.686	-1.34 number of errors Standard Error 2.858
Solanezumab: Cognitive Measures- Groton Maze Learning Test Delayed Reversed Recall Week 104	6.21 number of errors Standard Error 2.715	3.28 number of errors Standard Error 2.912
Solanezumab: Cognitive Measures- Groton Maze Learning Test Delayed Reversed Recall Week 156	6.45 number of errors Standard Error 2.490	1.82 number of errors Standard Error 2.711
Solanezumab: Cognitive Measures- Groton Maze Learning Test Delayed Reversed Recall Week 208	5.59 number of errors Standard Error 2.658	5.29 number of errors Standard Error 2.980
Solanezumab: Cognitive Measures- Groton Maze Learning Test Delayed Reversed Recall Week 260	14.25 number of errors Standard Error 10.722	6.75 number of errors Standard Error 15.509

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Trail Making test taps attention, processing speed, and executive function. Part A consists of 25 circles numbered 1 through 25 distributed over a white sheet of standard document-sized paper. The subject is instructed to connect the circles with a drawn line as quickly as possible in ascending numerical order without lifting their pen.

The subject's performance is judged in terms of the time, in seconds, required to complete each trail (Max time 150 seconds). Lower scores indicate more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- Trailmaking Test Part A Week 52	9.73 seconds Standard Error 2.895	5.14 seconds Standard Error 3.227
Solanezumab: Cognitive Measures- Trailmaking Test Part A Week 104	15.03 seconds Standard Error 4.473	11.38 seconds Standard Error 5.039
Solanezumab: Cognitive Measures- Trailmaking Test Part A Week 208	35.69 seconds Standard Error 11.028	32.63 seconds Standard Error 12.430
Solanezumab: Cognitive Measures- Trailmaking Test Part A Week 156	19.45 seconds Standard Error 5.832	15.21 seconds Standard Error 6.538
Solanezumab: Cognitive Measures- Trailmaking Test Part A Week 260	93.49 seconds Standard Error 27.664	89.02 seconds Standard Error 32.699

SECONDARY outcome

Timeframe: Baseline, Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

This test taps attention, processing speed, and executive function and depends on visuo-motor and perceptual-scanning skills and also requires considerable cognitive flexibility in shifting from number to letter sets under time pressure. Part B consists of 25 circles, but these circles contain either numbers (1 through 13) or letters (A through L). The subject must connect the circles while alternating between numbers and letters in an ascending order (e.g., A to 1; 1 to B; B to 2; 2 to C).

The subject's performance is judged in terms of the time, in seconds, required to complete each Trail (Max of 300 seconds). Lower scores indicate more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- Trailmaking Test Part B Week 52	-2.39 number of seconds Standard Error 6.582	8.00 number of seconds Standard Error 7.371
Solanezumab: Cognitive Measures- Trailmaking Test Part B Week 104	-0.20 number of seconds Standard Error 7.626	10.52 number of seconds Standard Error 8.710
Solanezumab: Cognitive Measures- Trailmaking Test Part B Week 156	21.59 number of seconds Standard Error 11.619	21.35 number of seconds Standard Error 13.470
Solanezumab: Cognitive Measures- Trailmaking Test Part B Week 208	21.42 number of seconds Standard Error 11.539	16.54 number of seconds Standard Error 13.211
Solanezumab: Cognitive Measures- Trailmaking Test Part B Week 260	53.44 number of seconds Standard Error 25.139	37.62 number of seconds Standard Error 33.565

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

This test engages multiple cognitive abilities, including attention, psychomotor speed, complex scanning, visual tracking, and immediate memory.

Scores range from 0-93 with higher scores indicate more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- WAIS-R Digit-Symbol Substitution Test Week 52	0.35 units on a scale Standard Error 1.149	-1.02 units on a scale Standard Error 1.283
Solanezumab: Cognitive Measures- WAIS-R Digit-Symbol Substitution Test Week 104	-0.97 units on a scale Standard Error 1.744	0.20 units on a scale Standard Error 1.965
Solanezumab: Cognitive Measures- WAIS-R Digit-Symbol Substitution Test Week 156	-3.64 units on a scale Standard Error 2.232	-1.72 units on a scale Standard Error 2.540
Solanezumab: Cognitive Measures- WAIS-R Digit-Symbol Substitution Test Week 208	-7.83 units on a scale Standard Error 2.784	-6.15 units on a scale Standard Error 3.170
Solanezumab: Cognitive Measures- WAIS-R Digit-Symbol Substitution Test Week 260	-12.96 units on a scale Standard Error 4.057	-9.60 units on a scale Standard Error 4.898

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Widely used measure of working memory (or attention) in which the subject is read number sequences of increasing length and then asked to repeat each sequence backward. The primary measure of performance is the number of digit sequences correctly reversed.

The unit of measure is number of digit sequences correctly recalled and ranges from 0-12. Higher scores indicate more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- WMS-R Digit Span Backward Week 52	0.06 number of correct sequences recalled Standard Error 0.241	-0.12 number of correct sequences recalled Standard Error 0.267
Solanezumab: Cognitive Measures- WMS-R Digit Span Backward Week 104	-0.41 number of correct sequences recalled Standard Error 0.272	-0.16 number of correct sequences recalled Standard Error 0.310
Solanezumab: Cognitive Measures- WMS-R Digit Span Backward Week 156	-1.14 number of correct sequences recalled Standard Error 0.370	-0.28 number of correct sequences recalled Standard Error 0.415
Solanezumab: Cognitive Measures- WMS-R Digit Span Backward Week 208	-1.17 number of correct sequences recalled Standard Error 0.460	-0.68 number of correct sequences recalled Standard Error 0.513
Solanezumab: Cognitive Measures- WMS-R Digit Span Backward Week 260	-1.17 number of correct sequences recalled Standard Error 0.657	-1.22 number of correct sequences recalled Standard Error 0.832

SECONDARY outcome

Timeframe: Baseline, Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

This is a widely-used test of working memory in which the subject is read number sequences of increasing length and asked to repeat them. The total score is the number of sequences correctly repeated.

The unit of measure is number of digit sequences correctly recalled and ranges from 0-12. Higher scores indicate more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- WMS-R Digit Span Forward Week 52	-0.76 number of correct sequences recalled Standard Error 0.220	-0.38 number of correct sequences recalled Standard Error 0.242
Solanezumab: Cognitive Measures- WMS-R Digit Span Forward Week 104	-1.03 number of correct sequences recalled Standard Error 0.290	-0.84 number of correct sequences recalled Standard Error 0.329
Solanezumab: Cognitive Measures- WMS-R Digit Span Forward Week 156	-1.50 number of correct sequences recalled Standard Error 0.346	-1.23 number of correct sequences recalled Standard Error 0.387
Solanezumab: Cognitive Measures- WMS-R Digit Span Forward Week 208	-1.96 number of correct sequences recalled Standard Error 0.424	-1.86 number of correct sequences recalled Standard Error 0.475
Solanezumab: Cognitive Measures- WMS-R Digit Span Forward Week 260	-2.05 number of correct sequences recalled Standard Error 0.722	-1.06 number of correct sequences recalled Standard Error 0.929

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

This is a measure of fluid intelligence. This test is used to get an estimate of the subjects IQ at baseline. Subjects are asked to complete a visual pattern by circling one of six response choices.

Scores range from 0-12 with higher scores indicating more favorable cognitive performance.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- Raven's Progressive Matrices (Set A) Week 52	-0.47 units on a scale Standard Error 0.235	-0.70 units on a scale Standard Error 0.261
Solanezumab: Cognitive Measures- Raven's Progressive Matrices (Set A) Week 104	-0.93 units on a scale Standard Error 0.310	-0.63 units on a scale Standard Error 0.350
Solanezumab: Cognitive Measures- Raven's Progressive Matrices (Set A) Week 156	-1.38 units on a scale Standard Error 0.366	-1.06 units on a scale Standard Error 0.408
Solanezumab: Cognitive Measures- Raven's Progressive Matrices (Set A) Week 208	-1.44 units on a scale Standard Error 0.372	-1.53 units on a scale Standard Error 0.416
Solanezumab: Cognitive Measures- Raven's Progressive Matrices (Set A) Week 260	-3.11 units on a scale Standard Error 0.873	-1.78 units on a scale Standard Error 1.124

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Category Fluency is a widely used measure of semantic memory (verbal fluency, language). The subject is asked to name different exemplars of a given semantic category (animals), and the number of unique exemplars named is scored.

Higher scores indicate more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- Category Fluency (Animals) Week 52	-1.86 units on a scale Standard Error 0.642	-2.19 units on a scale Standard Error 0.711
Solanezumab: Cognitive Measures- Category Fluency (Animals) Week 104	-1.64 units on a scale Standard Error 0.754	-2.50 units on a scale Standard Error 0.860
Solanezumab: Cognitive Measures- Category Fluency (Animals) Week 156	-2.84 units on a scale Standard Error 0.869	-2.46 units on a scale Standard Error 0.974
Solanezumab: Cognitive Measures- Category Fluency (Animals) Week 208	-4.69 units on a scale Standard Error 1.105	-3.27 units on a scale Standard Error 1.239
Solanezumab: Cognitive Measures- Category Fluency (Animals) Week 260	-5.45 units on a scale Standard Error 1.761	-6.50 units on a scale Standard Error 2.303

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Category Fluency is a widely used measure of semantic memory (verbal fluency, language). The subject is asked to name different exemplars of a given semantic category (vegetables), and the number of unique exemplars named is scored.

Higher scores indicate more favorable cognitive function.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- Category Fluency (Vegetables) Week 52	-0.83 units on a scale Standard Error 0.481	-1.41 units on a scale Standard Error 0.533
Solanezumab: Cognitive Measures- Category Fluency (Vegetables) Week 104	-1.22 units on a scale Standard Error 0.539	-1.74 units on a scale Standard Error 0.619
Solanezumab: Cognitive Measures- Category Fluency (Vegetables) Week 156	-1.29 units on a scale Standard Error 0.555	-1.43 units on a scale Standard Error 0.623
Solanezumab: Cognitive Measures- Category Fluency (Vegetables) Week 208	-2.03 units on a scale Standard Error 0.707	-1.72 units on a scale Standard Error 0.794
Solanezumab: Cognitive Measures- Category Fluency (Vegetables) Week 260	-3.36 units on a scale Standard Error 1.069	-2.23 units on a scale Standard Error 1.386

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Measure of delayed recall (episodic memory) of a story read to the subject at the beginning of the testing session and subject is asked to relay the story 20 minutes later.

Scores range from 0-25 with higher scores indicating more favorable cognitive performance.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- WMS-R Logical Memory Delayed Recall Test Week 52	0.64 units on a scale Standard Error 0.397	1.33 units on a scale Standard Error 0.441
Solanezumab: Cognitive Measures- WMS-R Logical Memory Delayed Recall Test Week 104	1.25 units on a scale Standard Error 0.501	1.71 units on a scale Standard Error 0.576
Solanezumab: Cognitive Measures- WMS-R Logical Memory Delayed Recall Test Week 156	1.21 units on a scale Standard Error 0.549	2.37 units on a scale Standard Error 0.618
Solanezumab: Cognitive Measures- WMS-R Logical Memory Delayed Recall Test Week 208	0.84 units on a scale Standard Error 0.606	1.82 units on a scale Standard Error 0.678
Solanezumab: Cognitive Measures- WMS-R Logical Memory Delayed Recall Test Week 260	0.40 units on a scale Standard Error 1.029	2.68 units on a scale Standard Error 1.416

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

This test assesses the ability to recall a short story. The subject is read a short story and immediately after hearing the story, the subject is asked to retell the story from memory.

Scores range from 0-25 with higher scores indicating more favorable cognitive performance.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- WMS-R Logical Memory Immediate Recall Test Week 208	0.24 units on a scale Standard Error 0.631	0.69 units on a scale Standard Error 0.707
Solanezumab: Cognitive Measures- WMS-R Logical Memory Immediate Recall Test Week 260	-0.56 units on a scale Standard Error 1.018	1.37 units on a scale Standard Error 1.420
Solanezumab: Cognitive Measures- WMS-R Logical Memory Immediate Recall Test Week 52	0.40 units on a scale Standard Error 0.452	-0.06 units on a scale Standard Error 0.501
Solanezumab: Cognitive Measures- WMS-R Logical Memory Immediate Recall Test Week 104	0.73 units on a scale Standard Error 0.510	0.75 units on a scale Standard Error 0.579
Solanezumab: Cognitive Measures- WMS-R Logical Memory Immediate Recall Test Week 156	0.13 units on a scale Standard Error 0.573	0.91 units on a scale Standard Error 0.646

SECONDARY outcome

Timeframe: Baseline through Week 260

Population: The endpoint itself is a ratio based on feeding z-scores for four separate parameters into a model, with programming providing the ratio under model assumptions rather than providing a treatment-specific value this is used to generate the ratio. The four individual parameters are described in other outcomes. There are no "by-arm" values for any MDPM analysis.

Multivariate Disease Progression Model adjusted for estimated years from symptom onset (EYO) and includes all time points up to treatment discontinuation. The treatment effect for Solanezumab is reported relative to the mutation positive placebo arm.

This alternative multivariate endpoint includes four tests: Logical Memory Immediate Recall, Digit Span Backward Recall, Category Fluency (Animals), Trailmaking Test Part B. Measurements for each test will be normalized using the mean (SD) at DIAN-TU-001 baseline among mutation negative subjects before being analyzed. For the Trailmaking Test B, the scores will be multiplied by -1 as higher scores indicate worse performance; whereas for the other three, lower scores indicate worse performance. Therefore, on the standardized endpoints, lower scores indicate worse performance.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=160 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Cognitive Measures- Composite Including: Alternative Multivariate Composite: (1) Digit Span Backwards; (2) Logical Memory (Immediate); (3) Trailmaking B; (4) Category Fluency (Animals)	1.155 Ratio Standard Deviation 0.074	—

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

PiB Standardized Uptake Value Ratio ([11C]PiB SUVR) is the most common quantitative method used to make regional comparisons within a subject as well as between subjects and computed as the degree of radiotracer uptake in a target region of interest (regions dervived via automated segmentation using FreeSurfer) with respect to a reference region. In amyloid and tau imaging, SUVR is typically generated using some portion or the entire cerebellum as a reference because cerebellum is not affected until late in the progression of AD.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Imaging Measures- Brain Amyloid Load as Measured by [11C]PiB-PET Non-partial Volume Corrected Week 52	0.030 Ratio Standard Error 0.0147	0.025 Ratio Standard Error 0.0164
Solanezumab: Imaging Measures- Brain Amyloid Load as Measured by [11C]PiB-PET Non-partial Volume Corrected Week 104	0.019 Ratio Standard Error 0.0180	0.022 Ratio Standard Error 0.0200
Solanezumab: Imaging Measures- Brain Amyloid Load as Measured by [11C]PiB-PET Non-partial Volume Corrected Week 208	0.113 Ratio Standard Error 0.0387	0.093 Ratio Standard Error 0.0408

SECONDARY outcome

Timeframe: Weeks104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was notcollected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Florbetapir Standardized Uptake Value Ratio ([18F]AV-45 SUVR) is the most common quantitative method used to make regional comparisons within a subject as well as between subjects and computed as the degree of radiotracer uptake in a target region of interest (regions derivved via automated segmentation using FreeSurfer) with respect to a reference region. In amyloid and tau imaging, SUVR is typically generated using some portion or the entire cerebellum as a reference because cerebellum is not affected until late in the progression of AD.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Imaging Measures- Brain Amyloid Load as Measured by Florbetapir PET Week 104	0.066 Ratio Standard Error 0.0458	0.105 Ratio Standard Error 0.0511
Solanezumab: Imaging Measures- Brain Amyloid Load as Measured by Florbetapir PET Week 208	0.251 Ratio Standard Error 0.0717	0.168 Ratio Standard Error 0.0775

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

FDG Standardized Uptake Value Ratio ([18F]FDG SUVR) is the most common quantitative method used to make regional comparisons within a subject as well as between subjects and computed as the degree of radiotracer uptake in a target region of interest (regions derivved via automated segmentation using FreeSurfer) with respect to a reference region. In amyloid and tau imaging, SUVR is typically generated using some portion or the entire cerebellum as a reference because cerebellum is not affected until late in the progression of AD.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Imaging Measures- Brain Glucose Metabolism as Measured by Fluorodeoxyglucose (FDG)-PET Non-partial Volume Corrected Week 52	-0.021 Ratio Standard Error 0.0072	-0.030 Ratio Standard Error 0.0083
Solanezumab: Imaging Measures- Brain Glucose Metabolism as Measured by Fluorodeoxyglucose (FDG)-PET Non-partial Volume Corrected Week 104	-0.047 Ratio Standard Error 0.0063	-0.043 Ratio Standard Error 0.0074
Solanezumab: Imaging Measures- Brain Glucose Metabolism as Measured by Fluorodeoxyglucose (FDG)-PET Non-partial Volume Corrected Week 208	-0.074 Ratio Standard Error 0.0110	-0.074 Ratio Standard Error 0.0127

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Brain atrophy was defined by structural magnetic resonance imaging (MRI) A Magnetization Prepared - RApid Gradient Echo) (MPRAGE) sequence was processed using the Freesurfer software suite. This package provides volumes and thickness values for cortical regions and volumes for subcortical regions. For the clinical trial we examined cortical thickness values in prespecified regions of interest known to show atrophy in autosomal dominant Alzheimer Disease. Higher measurements are more favorable.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Cortical Thickness of Regions of Interest - Precuneus Region Week 52	-0.033 Millimeters Standard Error 0.0106	-0.053 Millimeters Standard Error 0.0114
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Cortical Thickness of Regions of Interest - Precuneus Region Week 104	-0.067 Millimeters Standard Error 0.0142	-0.090 Millimeters Standard Error 0.0156
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Cortical Thickness of Regions of Interest - Precuneus Region Week 156	-0.110 Millimeters Standard Error 0.0193	-0.122 Millimeters Standard Error 0.0214
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Cortical Thickness of Regions of Interest - Precuneus Region Week 208	-0.138 Millimeters Standard Error 0.0254	-0.154 Millimeters Standard Error 0.0279

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Brain atrophy was defined by structural magnetic resonance imaging (MRI) A Magnetization Prepared - RApid Gradient Echo) (MPRAGE) sequence was processed using the Freesurfer software suite. This package provides volumes and thickness values for cortical regions and volumes for subcortical regions. For the clinical trial we examined volume values in prespecified regions of interest known to show atrophy in autosomal dominant Alzheimer Disease.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Imaging Measures- Volumetric MRI Combined Total Volume Corrected for Head Size - Hippocampus Volume Week 52	-106.74 Cubic Millimeters Standard Error 71.081	-153.34 Cubic Millimeters Standard Error 78.529
Solanezumab: Imaging Measures- Volumetric MRI Combined Total Volume Corrected for Head Size - Hippocampus Volume Week 104	-341.35 Cubic Millimeters Standard Error 72.549	-302.58 Cubic Millimeters Standard Error 80.556
Solanezumab: Imaging Measures- Volumetric MRI Combined Total Volume Corrected for Head Size - Hippocampus Volume Week 156	-524.14 Cubic Millimeters Standard Error 76.210	-541.76 Cubic Millimeters Standard Error 84.861
Solanezumab: Imaging Measures- Volumetric MRI Combined Total Volume Corrected for Head Size - Hippocampus Volume Week 208	-706.41 Cubic Millimeters Standard Error 78.746	-671.95 Cubic Millimeters Standard Error 85.672
Solanezumab: Imaging Measures- Volumetric MRI Combined Total Volume Corrected for Head Size - Hippocampus Volume Week 260	-977.91 Cubic Millimeters Standard Error 116.633	-551.42 Cubic Millimeters Standard Error 137.366

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end). In addition, the tau tracer was not introduced in the trial until after baseline for most participants.

This variable represents how much neurofibrillary tau pathology is present in brain as assessed using positron emission tomography (PET). Scans were conducted using [F18] Flortaucipir, a commonly used tracer in the field.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Imaging Measures- Brain Tau Load as Measured by Flortaucipir PET Non-partial Volume Corrected Baseline	1.77391 Ratio Standard Deviation 0.548324	1.52502 Ratio Standard Deviation 0.582485
Solanezumab: Imaging Measures- Brain Tau Load as Measured by Flortaucipir PET Non-partial Volume Corrected Week 52	1.46020 Ratio Standard Deviation 0.503595	1.49041 Ratio Standard Deviation 0.434475
Solanezumab: Imaging Measures- Brain Tau Load as Measured by Flortaucipir PET Non-partial Volume Corrected Change in Baseline in Week 52	0.11302 Ratio Standard Deviation 0.221413	-0.03925 Ratio Standard Deviation 0.192448
Solanezumab: Imaging Measures- Brain Tau Load as Measured by Flortaucipir PET Non-partial Volume Corrected Week 104	1.49990 Ratio Standard Deviation 0.506423	1.42231 Ratio Standard Deviation 0.394000
Solanezumab: Imaging Measures- Brain Tau Load as Measured by Flortaucipir PET Non-partial Volume Corrected Change from Baseline Week 104	0.15450 Ratio Standard Deviation 0.252682	0.01208 Ratio Standard Deviation 0.263170
Solanezumab: Imaging Measures- Brain Tau Load as Measured by Flortaucipir PET Non-partial Volume Corrected Week 208	1.43263 Ratio Standard Deviation 0.402563	1.28081 Ratio Standard Deviation 0.295191
Solanezumab: Imaging Measures- Brain Tau Load as Measured by Flortaucipir PET Non-partial Volume Corrected Change from Baseline Week 208	0.05275 Ratio Standard Deviation 0.052679	0.05825 Ratio Standard Deviation 0.023688

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Brain atrophy was defined by structural magnetic resonance imaging (MRI) A Magnetization Prepared - RApid Gradient Echo) (MPRAGE) sequence was processed using the Freesurfer software suite. This package provides volumes and thickness values for cortical regions and volumes for subcortical regions. A whole brain volume measure was generated to represent global atrophy across the cortical and subcortical regions.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Whole Brain Volume Corrected for Head Size Week 52	-11990.31 Cubic Millimeters Standard Error 4027.589	-10578.56 Cubic Millimeters Standard Error 4409.442
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Whole Brain Volume Corrected for Head Size Week 104	-19808.05 Cubic Millimeters Standard Error 4106.838	-22147.27 Cubic Millimeters Standard Error 4524.072
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Whole Brain Volume Corrected for Head Size Week 156	-32713.22 Cubic Millimeters Standard Error 4304.849	-30590.95 Cubic Millimeters Standard Error 4770.402
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Whole Brain Volume Corrected for Head Size Week 208	-39306.90 Cubic Millimeters Standard Error 4446.803	-36569.28 Cubic Millimeters Standard Error 4816.319
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Whole Brain Volume Corrected for Head Size Week 260	-54558.23 Cubic Millimeters Standard Error 6562.583	-50077.53 Cubic Millimeters Standard Error 7713.907

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104, 156, 208 and 260

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Rather than looking at how tissue in the brain changes, it is also possible to quantify how the ventricles, fluid filled spaces in the brain, change. Increasing ventricular volume represents greater amounts of cerebral spinal fluid which suggests atrophy of the brain. Magnetization Prepared - RApid Gradient Echo) (MPRAGE) sequences were processed using the Freesurfer software suite. Total ventricular volume was calculated from the ventricular volumes generated by this program.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Ventricular Volume (Volumetric MRI) Corrected for Head Size Week 156	5705.59 Cubic Millimeters Standard Error 1163.978	6729.64 Cubic Millimeters Standard Error 1297.406
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Ventricular Volume (Volumetric MRI) Corrected for Head Size Week 52	1815.99 Cubic Millimeters Standard Error 1067.526	1796.78 Cubic Millimeters Standard Error 1182.631
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Ventricular Volume (Volumetric MRI) Corrected for Head Size Week 104	2972.85 Cubic Millimeters Standard Error 1094.409	4452.69 Cubic Millimeters Standard Error 1218.440
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Ventricular Volume (Volumetric MRI) Corrected for Head Size Week 208	8755.04 Cubic Millimeters Standard Error 1212.184	9833.37 Cubic Millimeters Standard Error 1312.937
Solanezumab: Imaging Measures- Brain Atrophy as Measured by Ventricular Volume (Volumetric MRI) Corrected for Head Size Week 260	12332.3 Cubic Millimeters Standard Error 1907.752	11456.61 Cubic Millimeters Standard Error 2258.240

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Measured concentration of the drug bound and free soluble Aβ1-40 peptide in cerebrospinal fluid using enzyme-linked immunosorbent assay (ELISA)

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=19 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- CSF Aβ 40 Free Change From Baseline Week 52	-1613.48 pg/mL Standard Error 185.134	-856.65 pg/mL Standard Error 284.584
Solanezumab: Fluid Biomarker Measures- CSF Aβ 40 Free Change From Baseline Week 104	-2237.73 pg/mL Standard Error 177.616	-1398.13 pg/mL Standard Error 290.994
Solanezumab: Fluid Biomarker Measures- CSF Aβ 40 Free Change From Baseline Week 208	-2567.13 pg/mL Standard Error 229.807	-631.22 pg/mL Standard Error 307.331

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Measured concentration of the total soluble Aβ 1-42 peptide in cerebrospinal fluid using ELISA

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=19 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- CSF Aβ 42 Free Week 52	-109.33 pg/mL Standard Error 24.235	-79.35 pg/mL Standard Error 37.602
Solanezumab: Fluid Biomarker Measures- CSF Aβ 42 Free Week 104	-172.55 pg/mL Standard Error 14.535	-125.64 pg/mL Standard Error 24.402
Solanezumab: Fluid Biomarker Measures- CSF Aβ 42 Free Week 208	-250.78 pg/mL Standard Error 13.935	-173.66 pg/mL Standard Error 18.204

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data was not collected for all participants at each time point for various reasons

Measured concentration of the soluble Tau peptide in cerebrospinal fluid

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- CSF Tau Week 52	4.73 pg/mL Standard Error 14.884	-6.60 pg/mL Standard Error 15.553
Solanezumab: Fluid Biomarker Measures- CSF Tau Week 104	31.74 pg/mL Standard Error 15.649	23.24 pg/mL Standard Error 16.783
Solanezumab: Fluid Biomarker Measures- CSF Tau Week 208	59.08 pg/mL Standard Error 24.691	28.19 pg/mL Standard Error 25.579

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data was not collected for all participants at each time point for various reasons

Measured concentration of phosphorylated tau at threonine-181 in cerebrospinal fluid

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- CSF pTau 181 Week 52	0.26 pg/mL Standard Error 2.951	-0.18 pg/mL Standard Error 3.254
Solanezumab: Fluid Biomarker Measures- CSF pTau 181 Week 104	4.91 pg/mL Standard Error 2.903	4.25 pg/mL Standard Error 3.290
Solanezumab: Fluid Biomarker Measures- CSF pTau 181 Week 208	6.90 pg/mL Standard Error 4.447	7.65 pg/mL Standard Error 4.907

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Measured concentration of neurofilament light chain in cerebrospinal fluid using SIMO

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Change From Baseline Fluid Biomarker Measures- CSF Neurofilament Light Chain (NfL) Week 52	0.102 pg/mL Standard Error 0.0414	0.144 pg/mL Standard Error 0.0463
Solanezumab: Change From Baseline Fluid Biomarker Measures- CSF Neurofilament Light Chain (NfL) Week 104	0.191 pg/mL Standard Error 0.0314	0.159 pg/mL Standard Error 0.0354
Solanezumab: Change From Baseline Fluid Biomarker Measures- CSF Neurofilament Light Chain (NfL) Week 208	0.426 pg/mL Standard Error 0.0402	0.248 pg/mL Standard Error 0.0435

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data was not collected for all participants at each time point for various reasons

Measured concentration of neurofilamnet light chain in plasma using Single Molecule Array (SIMOA)

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- Plasma Neurofilament Light Chain (NfL) Week 208	3.29 pg/mL Standard Error 0.959	3.72 pg/mL Standard Error 0.960
Solanezumab: Fluid Biomarker Measures- Plasma Neurofilament Light Chain (NfL) Week 52	0.47 pg/mL Standard Error 1.864	4.03 pg/mL Standard Error 1.893
Solanezumab: Fluid Biomarker Measures- Plasma Neurofilament Light Chain (NfL) Week 104	1.22 pg/mL Standard Error 0.799	3.15 pg/mL Standard Error 0.780

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Measurement of the presence or absence of anti-drug antibodies in serum

Note: Mutation Negative Placebo subjects are not displayed as anti-drug antibody testing was not to be evaluated for these subjects.

Note: Treatment Emergent Anti-Drug Antibody Positive subjects are defined as those with either (a) a baseline status of ADA Not Present and at least one post-baseline ADA present with a titer >= 1:20 or (b) both a baseline and post-baseline status of ADA Present with the post-baseline titer being 2 dilutions (4-fold) greater than the baseline titer.

Note: Treatment Emergent Anti-Drug Antibody Inconclusive subjects are defined as those for whom >=20% of the subject's post-baseline ADA results are ADA Inconclusive and all remaining post-baseline samples are ADA Not Present.

Note: Treatment Emergent Anti-Drug Antibody Negative subjects are defined as those who are evaluable for TE ADA but are neither TE ADA Positive nor TE ADA Inconclusive.

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=52 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=40 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 52 : Detected	4 Participants	3 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 52 : Detected Titer 1:80	1 Participants	0 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 208 : Not Detected	33 Participants	24 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Treatment Emergent ADA Inconclusive	0 Participants	0 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Treatment Emergent ADA Negative	44 Participants	25 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 52 : Detected Titer 1:10	3 Participants	2 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 52 : Detected Titer 1:20	0 Participants	1 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 104 : Not Detected	40 Participants	29 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 104 : Detected	3 Participants	3 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 104 : Detected Titer 1:10	0 Participants	2 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 104 : Detected Titer 1:20	1 Participants	1 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 104 : Detected Titer 1:80	1 Participants	0 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 104 : Detected Titer 1:320	1 Participants	0 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 208 : Detected	2 Participants	2 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 208 : Detected Titer 1:10	1 Participants	1 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 208 : Detected Titer 1:20	1 Participants	1 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Treatment Emergent ADA Positive	2 Participants	0 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) >=1 Positive Neutralizing Antibody Result	0 Participants	0 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Week 52 : Not Detected	44 Participants	32 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Baseline : Not Detected	43 Participants	22 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Baseline : Detected	3 Participants	3 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Baseline: Detected Titer 1:10	2 Participants	3 Participants
Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA) Baseline: Detected Titer 1:20	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data was not collected for all participants at each time point for various reasons

Measured concentration of the total soluble Aβ 1-40 peptide in cerebrospinal fluid using ELISA

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=19 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- Total Plasma Aβ 1-40 Week 52	168588.48 pg/mL Standard Error 5889.151	-9257.53 pg/mL Standard Error 9091.376
Solanezumab: Fluid Biomarker Measures- Total Plasma Aβ 1-40 Week 104	165220.34 pg/mL Standard Error 5425.379	-9263.35 pg/mL Standard Error 9010.529
Solanezumab: Fluid Biomarker Measures- Total Plasma Aβ 1-40 Week 208	220136.05 pg/mL Standard Error 8168.936	-9226.25 pg/mL Standard Error 12358.817

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Measured concentration of the total soluble Aβ 1-42 peptide in cerebrospinal fluid using ELISA

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=19 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- Total Plasma Aβ 42 Week 52	30609.39 pg/mL Standard Error 1555.170	526.91 pg/mL Standard Error 2334.054
Solanezumab: Fluid Biomarker Measures- Total Plasma Aβ 42 Week 104	29265.35 pg/mL Standard Error 1459.112	746.90 pg/mL Standard Error 2424.659
Solanezumab: Fluid Biomarker Measures- Total Plasma Aβ 42 Week 208	33744.89 pg/mL Standard Error 922.711	838.29 pg/mL Standard Error 1415.925

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Measured concentration of the total soluble Aβ1-42 peptide in cerebrospinal fluid using enzyme-linked immunosorbent assay (ELISA)

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=19 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- CSF Aβ 42 Total Week 52	558.91 pg/mL Standard Error 44.533	44.81 pg/mL Standard Error 69.142
Solanezumab: Fluid Biomarker Measures- CSF Aβ 42 Total Week 104	623.16 pg/mL Standard Error 41.301	89.32 pg/mL Standard Error 68.119
Solanezumab: Fluid Biomarker Measures- CSF Aβ 42 Total Week 208	1352.83 pg/mL Standard Error 75.447	66.48 pg/mL Standard Error 118.662

SECONDARY outcome

Timeframe: Baseline and Weeks 52, 104 and 208

Population: Number analyzed represents actual data collections at each collection time point. Data unavailable at any time point was not collected for various reasons i.e. participant attrition or common close design (participants did not reach that time point before trial end).

Measured concentration of the total soluble Aβ1-40 peptide in cerebrospinal fluid using enzyme-linked immunosorbent assay (ELISA)

Outcome measures

Measure	Gantenerumab vs. Mutation Positive Placebo n=50 Participants Gantenerumab: Subcutaneously every 4 weeks at escalating doses; Matching Placebo	Solanezumab vs. Mutation Positive Placebo n=19 Participants Solanezumab: Intravenous infusion every 4 weeks at escalating doses; Matching Placebo
Solanezumab: Fluid Biomarker Measures- CSF Aβ 40 Total Week 52	3676.97 pg/mL Standard Error 403.908	-414.57 pg/mL Standard Error 625.000
Solanezumab: Fluid Biomarker Measures- CSF Aβ 40 Total Week 104	4017.93 pg/mL Standard Error 331.917	-594.08 pg/mL Standard Error 549.240
Solanezumab: Fluid Biomarker Measures- CSF Aβ 40 Total Week 208	9723.95 pg/mL Standard Error 669.037	-143.31 pg/mL Standard Error 1011.672

Adverse Events

Gantenerumab

Serious events: 12 serious events

Other events: 52 other events

Deaths: 0 deaths

Solanezumab

Serious events: 13 serious events

Other events: 52 other events

Deaths: 0 deaths

Placebo

Serious events: 12 serious events

Other events: 89 other events

Deaths: 0 deaths

DIAN OBS Control Group

Serious events: 10 serious events

Other events: 57 other events

Deaths: 1 deaths

Combined Blinded

Serious events: 47 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Gantenerumab n=52 participants at risk Gantenerumab Active Treatment: Dosing subcutaneously every 4 weeks at escalating doses	Solanezumab n=52 participants at risk Solanezumab Active Treatment: Dosing by intravenous infusion every 4 weeks at escalating doses	Placebo n=89 participants at risk All placebos including mutation negative and positive	DIAN OBS Control Group n=69 participants at risk Participants in the DIAN-OBS study who met DIAN-TU inclusion criteria were used as natural history controls for improved estimates of the placebo group. DIAN-OBS participants were included based on specific criteria as outlined in the SAP; included at the first visit where eligibility was met which means their period of eligibility would not match the full period of time as the DIAN-TU-001 placebo participants.	Combined Blinded n=262 participants at risk All arms/groups combined for the purpose of maintaining blinding for participant mutation status and treatment group.
General disorders General disorders	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	1.1% 3/262 • Number of events 3 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Gastrointestinal disorders Gastrointestinal disorders	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	2.7% 7/262 • Number of events 8 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Infections and infestations Infections and infestations	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	3.4% 9/262 • Number of events 9 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	5.3% 14/262 • Number of events 16 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	2.3% 6/262 • Number of events 6 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	1.1% 3/262 • Number of events 3 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Nervous system disorders Nervous system disorders	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	4.2% 11/262 • Number of events 12 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Psychiatric disorders Psychiatric disorders	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	1.5% 4/262 • Number of events 4 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Renal and urinary disorders Renal and urinary disorders	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	1.1% 3/262 • Number of events 3 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Reproductive system and breast disorders Reproductive system and breast disorders	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.76% 2/262 • Number of events 2 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.76% 2/262 • Number of events 2 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.76% 2/262 • Number of events 2 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality

Other adverse events

Measure	Gantenerumab n=52 participants at risk Gantenerumab Active Treatment: Dosing subcutaneously every 4 weeks at escalating doses	Solanezumab n=52 participants at risk Solanezumab Active Treatment: Dosing by intravenous infusion every 4 weeks at escalating doses	Placebo n=89 participants at risk All placebos including mutation negative and positive	DIAN OBS Control Group n=69 participants at risk Participants in the DIAN-OBS study who met DIAN-TU inclusion criteria were used as natural history controls for improved estimates of the placebo group. DIAN-OBS participants were included based on specific criteria as outlined in the SAP; included at the first visit where eligibility was met which means their period of eligibility would not match the full period of time as the DIAN-TU-001 placebo participants.	Combined Blinded n=262 participants at risk All arms/groups combined for the purpose of maintaining blinding for participant mutation status and treatment group.
Cardiac disorders Cardiac Disorders	7.7% 4/52 • Number of events 5 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	1.9% 1/52 • Number of events 2 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	10.1% 9/89 • Number of events 13 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Ear and labyrinth disorders Ear and labyrinth disorders	15.4% 8/52 • Number of events 8 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	11.5% 6/52 • Number of events 8 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	12.4% 11/89 • Number of events 17 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Eye disorders Eye Disorders	23.1% 12/52 • Number of events 18 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	3.8% 2/52 • Number of events 3 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	10.1% 9/89 • Number of events 11 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Gastrointestinal disorders Gastrointestinal disorders	63.5% 33/52 • Number of events 115 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	67.3% 35/52 • Number of events 88 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	53.9% 48/89 • Number of events 133 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
General disorders General disorders and administration site conditions	96.2% 50/52 • Number of events 1066 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	59.6% 31/52 • Number of events 70 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	60.7% 54/89 • Number of events 262 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Immune system disorders Immune system disorders	9.6% 5/52 • Number of events 6 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	15.4% 8/52 • Number of events 10 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	9.0% 8/89 • Number of events 9 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	69.2% 36/52 • Number of events 92 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	67.3% 35/52 • Number of events 85 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	58.4% 52/89 • Number of events 146 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	39.1% 27/69 • Number of events 35 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Investigations Investigations	30.8% 16/52 • Number of events 31 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	23.1% 12/52 • Number of events 19 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	33.7% 30/89 • Number of events 55 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Metabolism and nutrition disorders Metabolism and nutrition disorders	13.5% 7/52 • Number of events 11 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	11.5% 6/52 • Number of events 7 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	15.7% 14/89 • Number of events 17 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	57.7% 30/52 • Number of events 95 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	53.8% 28/52 • Number of events 89 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	58.4% 52/89 • Number of events 140 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	36.2% 25/69 • Number of events 38 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	11.5% 6/52 • Number of events 7 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	9.6% 5/52 • Number of events 7 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	4.5% 4/89 • Number of events 5 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Nervous system disorders Nervous system disorders	78.8% 41/52 • Number of events 192 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	73.1% 38/52 • Number of events 175 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	65.2% 58/89 • Number of events 276 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	43.5% 30/69 • Number of events 48 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Psychiatric disorders Psychiatric disorders	42.3% 22/52 • Number of events 55 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	55.8% 29/52 • Number of events 51 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	32.6% 29/89 • Number of events 50 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Renal and urinary disorders Renal and urinary disorders	9.6% 5/52 • Number of events 6 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	7.7% 4/52 • Number of events 5 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	6.7% 6/89 • Number of events 7 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Reproductive system and breast disorders Reproductive system and breast disorders	13.5% 7/52 • Number of events 7 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	11.5% 6/52 • Number of events 7 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	9.0% 8/89 • Number of events 10 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	46.2% 24/52 • Number of events 54 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	42.3% 22/52 • Number of events 64 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	37.1% 33/89 • Number of events 91 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	44.2% 23/52 • Number of events 52 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	34.6% 18/52 • Number of events 36 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	32.6% 29/89 • Number of events 49 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Vascular disorders Vascular disorders	15.4% 8/52 • Number of events 10 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	9.6% 5/52 • Number of events 7 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	14.6% 13/89 • Number of events 18 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Infections and infestations Infections and infestations	75.0% 39/52 • Number of events 180 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	78.8% 41/52 • Number of events 170 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	69.7% 62/89 • Number of events 223 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality
Social circumstances Social Circumstances	5.8% 3/52 • Number of events 4 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	5.8% 3/52 • Number of events 3 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	5.6% 5/89 • Number of events 7 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	0.00% 0/69 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality	— 0/0 • AE data was collected from consenting up to post study follow-up 8-12 weeks after last dose, approximately 6 years overall. In order to protect the genetic blinding requested by participants, as well as treatment assignment in the double-blind period to protect integrity of the ongoing open-label extension, the following precautions have been taken: 1) All Other (Not Including Serious) AEs have been reported by the higher level SOC; 2) SAEs have been summarized per arm at the general organ system level, and additionally at the subject level using a combined Arm/Group necessary to preserve participant confidentiality

Additional Information

Administrative Director

Washington University

Phone: (314) 221-8344

Email: DIAN-TUDataRequest@wustl.edu

Results disclosure agreements

• Principal investigator is a sponsor employee PI's may publish data and study results individually after the earlier of: 1) multi-center Publication is published; 2) no multi-center publication is submitted within 18 months after conclusion, abandonment, or termination of the Protocol at all sites; or 3) sponsor confirms in writing there will be no multi-center Publication. PI must submit results communications to the sponsor at least 75 days prior to submission or presentation. Sponsor can require changes to the communication.
• Publication restrictions are in place

Restriction type: OTHER