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 NCT06424236)

Last Updated: 2025-02-04

Results Overview

The composite PiB partial volume corrected C-SUVR was used as the biomarker endpoint for amyloid deposition using PET. The C-SUVR of precuneus, caudate, gyrus rectus, occipital cortex, parietal cortex, prefrontal cortex, and temporal cortex of brain regions was analyzed. Higher ratio indicate worse disease stage. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

73 participants

Primary outcome timeframe

Baseline (Day 1) and Weeks 52, 104 and 156

Results posted on

2025-02-04

Participant Flow

This is a open-label period of the trial following a Phase II/III double-blind, placebo-controlled study conducted in participants with, or at risk for, dominantly inherited Alzheimer's disease at 17 sites in the United States, Canada, Australia and Europe between 03 June 2020 and 13 November 2023.

All eligible participants from DIAN-TU-001 trial sites were offered the opportunity to receive gantenerumab for up to 3 years in an open-label extension (OLE). A total of 74 participants were enrolled in the OLE period of which, 1 participant was screen failure.

Participant milestones

Participant milestones
Measure	Double-blind Placebo - OLE Gantenerumab Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 milligram (mg) subcutaneous (SC) infusion every 2 weeks (Q2W) for 3 years.	Double-blind Solanezumab - OLE Gantenerumab Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Overall Study STARTED	18	27	28
Overall Study COMPLETED	4	2	7
Overall Study NOT COMPLETED	14	25	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Double-blind Placebo - OLE Gantenerumab Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 milligram (mg) subcutaneous (SC) infusion every 2 weeks (Q2W) for 3 years.	Double-blind Solanezumab - OLE Gantenerumab Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Overall Study Adverse Event	0	1	0
Overall Study Withdrawal by Subject	3	1	2
Overall Study Physician Decision	0	1	0
Overall Study Study Terminated by Sponsor	11	20	16
Overall Study Lost to Follow-up	0	1	0
Overall Study Disease Progression	0	1	2
Overall Study Other	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-blind Placebo - OLE Gantenerumab n=18 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=27 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=28 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Total n=73 Participants Total of all reporting groups
Age, Continuous	49.7 years STANDARD_DEVIATION 9.62 • n=99 Participants	47.0 years STANDARD_DEVIATION 8.60 • n=107 Participants	50.3 years STANDARD_DEVIATION 7.97 • n=206 Participants	48.9 years STANDARD_DEVIATION 8.64 • n=7 Participants
Sex: Female, Male Female	11 Participants n=99 Participants	14 Participants n=107 Participants	13 Participants n=206 Participants	38 Participants n=7 Participants
Sex: Female, Male Male	7 Participants n=99 Participants	13 Participants n=107 Participants	15 Participants n=206 Participants	35 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=99 Participants	1 Participants n=107 Participants	4 Participants n=206 Participants	9 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=99 Participants	26 Participants n=107 Participants	24 Participants n=206 Participants	64 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race/Ethnicity, Customized White	14 Participants n=99 Participants	26 Participants n=107 Participants	26 Participants n=206 Participants	66 Participants n=7 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islanders	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race/Ethnicity, Customized Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race/Ethnicity, Customized Other	4 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	6 Participants n=7 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Weeks 52, 104 and 156

Population: The OLE gantenerumab modified intent-to-treat (mITT) analysis set included all participants in the OLE who met mITT criteria using OLE baseline as the baseline reference point. Only participants analyzed at baseline and specific timepoints are reported.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=12 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=20 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=20 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in Composite [11C] Pittsburgh Compound B (PiB)-Positron Emission Tomography (PET) Composite Standardized Uptake Value Ratio (C-SUVR) at Weeks 52, 104 and 156 Week 52	-0.1382 ratio Standard Deviation 0.22606	-0.3318 ratio Standard Deviation 0.40538	0.1201 ratio Standard Deviation 0.15142
Change From Baseline in Composite [11C] Pittsburgh Compound B (PiB)-Positron Emission Tomography (PET) Composite Standardized Uptake Value Ratio (C-SUVR) at Weeks 52, 104 and 156 Week 104	-0.4843 ratio Standard Deviation 0.55217	-0.7026 ratio Standard Deviation 0.63641	-0.1880 ratio Standard Deviation 0.26639
Change From Baseline in Composite [11C] Pittsburgh Compound B (PiB)-Positron Emission Tomography (PET) Composite Standardized Uptake Value Ratio (C-SUVR) at Weeks 52, 104 and 156 Week 156	-0.7660 ratio Standard Deviation 0.64108	-1.1761 ratio Standard Deviation 0.96831	-0.2748 ratio Standard Deviation 0.41027

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 52, 104 and 156

Population: The OLE gantenerumab mITT analysis set included all participants in the OLE who met mITT criteria using OLE baseline as the baseline reference point. Only participants analyzed at baseline and specific timepoints are reported.

The efficacy of gantenerumab in reducing disease progression was assessed by CDR - sum of boxes. The CDR-SB score is considered a more detailed quantitative general index of cognition and function than the global CDR score. The CDR - sum of boxes is the sum score of 6 domains of cognitive function (memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care), with the score of each domain ranging from 0 (no impairment) to 3 (severe impairment). The total score ranges from 0 (no impairment) to 18 (severe impairment). Higher score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=17 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=23 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=22 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in Clinical Dementia Rating (CDR) - Sum of Boxes Score at Weeks 52, 104 and 156 Week 52	1.12 score on a scale Standard Deviation 2.147	0.91 score on a scale Standard Deviation 1.497	0.09 score on a scale Standard Deviation 0.666
Change From Baseline in Clinical Dementia Rating (CDR) - Sum of Boxes Score at Weeks 52, 104 and 156 Week 104	1.47 score on a scale Standard Deviation 2.191	1.31 score on a scale Standard Deviation 2.507	0.50 score on a scale Standard Deviation 1.504
Change From Baseline in Clinical Dementia Rating (CDR) - Sum of Boxes Score at Weeks 52, 104 and 156 Week 156	2.15 score on a scale Standard Deviation 3.504	0.40 score on a scale Standard Deviation 0.907	1.14 score on a scale Standard Deviation 2.405

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 52, 104 and 156

The efficacy of gantenerumab in reducing disease progression was assessed by CDR - global score. The score ranges from 0 (minimum) to 3 (maximum). Higher score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=17 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=23 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=22 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in Clinical Dementia Rating - Global Score at Weeks 52, 104 and 156 Week 52	0.12 score on a scale Standard Deviation 0.281	0.17 score on a scale Standard Deviation 0.324	0.02 score on a scale Standard Deviation 0.188
Change From Baseline in Clinical Dementia Rating - Global Score at Weeks 52, 104 and 156 Week 104	0.17 score on a scale Standard Deviation 0.309	0.21 score on a scale Standard Deviation 0.514	0.09 score on a scale Standard Deviation 0.366
Change From Baseline in Clinical Dementia Rating - Global Score at Weeks 52, 104 and 156 Week 156	0.25 score on a scale Standard Deviation 0.425	0.10 score on a scale Standard Deviation 0.211	0.18 score on a scale Standard Deviation 0.421

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 52, 104 and 156

The efficacy of gantenerumab in reducing disease progression was assessed by FAS. This scale measured instrumental activities of daily living such as preparing balanced meals and managing personal finances. The intent of the FAS was to assess change in an individual's functional activities, relative to previously attained abilities, that were caused by cognitive dysfunction. The score ranges from 0 (minimum) to 30 (maximum). Higher score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=15 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=22 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=23 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in Functional Assessment Scale (FAS) at Weeks 52, 104 and 156 Week 52	1.7555 score on a scale Standard Deviation 3.25466	1.1060 score on a scale Standard Deviation 2.80472	0.4348 score on a scale Standard Deviation 1.67403
Change From Baseline in Functional Assessment Scale (FAS) at Weeks 52, 104 and 156 Week 104	3.1885 score on a scale Standard Deviation 5.48051	1.9524 score on a scale Standard Deviation 3.85326	0.8889 score on a scale Standard Deviation 2.71006
Change From Baseline in Functional Assessment Scale (FAS) at Weeks 52, 104 and 156 Week 156	2.1944 score on a scale Standard Deviation 3.37680	1.0000 score on a scale Standard Deviation 2.39046	1.6154 score on a scale Standard Deviation 3.37980

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 24, 52, 76, 104, 128 and 156

The efficacy of gantenerumab in reducing disease progression was assessed by MMSE. The MMSE is a brief, quantitative measure of cognitive status in adults used to screen for cognitive impairment. The score ranges from 0 (minimum) to 30 (maximum). Lower score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=17 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=24 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=24 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in Mini-Mental State Examination (MMSE) at Weeks 24, 52, 76, 104, 128 and 156 Week 104	-3.1 score on a scale Standard Deviation 5.13	-1.5 score on a scale Standard Deviation 4.73	-1.2 score on a scale Standard Deviation 3.53
Change From Baseline in Mini-Mental State Examination (MMSE) at Weeks 24, 52, 76, 104, 128 and 156 Week 24	-0.6 score on a scale Standard Deviation 2.40	-0.5 score on a scale Standard Deviation 3.00	-0.1 score on a scale Standard Deviation 1.23
Change From Baseline in Mini-Mental State Examination (MMSE) at Weeks 24, 52, 76, 104, 128 and 156 Week 52	-1.2 score on a scale Standard Deviation 2.74	-1.0 score on a scale Standard Deviation 2.47	-0.9 score on a scale Standard Deviation 2.35
Change From Baseline in Mini-Mental State Examination (MMSE) at Weeks 24, 52, 76, 104, 128 and 156 Week 76	-2.1 score on a scale Standard Deviation 3.70	-0.8 score on a scale Standard Deviation 3.51	-0.9 score on a scale Standard Deviation 2.89
Change From Baseline in Mini-Mental State Examination (MMSE) at Weeks 24, 52, 76, 104, 128 and 156 Week 128	-3.3 score on a scale Standard Deviation 5.50	-0.2 score on a scale Standard Deviation 1.93	-2.1 score on a scale Standard Deviation 4.71
Change From Baseline in Mini-Mental State Examination (MMSE) at Weeks 24, 52, 76, 104, 128 and 156 Week 156	-3.8 score on a scale Standard Deviation 7.61	1.2 score on a scale Standard Deviation 1.33	-1.4 score on a scale Standard Deviation 3.92

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 52, 104 and 156

The efficacy of gantenerumab in reducing disease progression was assessed by Tau PET SUVR. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=12 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=14 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=16 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in Tau Positron Emission Tomography Binding Partial Volume Corrected Standardized Uptake Value Ratio (Tau PET SUVR) at Weeks 52, 104 and 156 Week 52	0.09032 ratio Standard Deviation 0.337016	-0.11554 ratio Standard Deviation 0.537111	0.12246 ratio Standard Deviation 0.202397
Change From Baseline in Tau Positron Emission Tomography Binding Partial Volume Corrected Standardized Uptake Value Ratio (Tau PET SUVR) at Weeks 52, 104 and 156 Week 104	0.29471 ratio Standard Deviation 0.658922	0.19329 ratio Standard Deviation 0.811715	0.26572 ratio Standard Deviation 0.314147
Change From Baseline in Tau Positron Emission Tomography Binding Partial Volume Corrected Standardized Uptake Value Ratio (Tau PET SUVR) at Weeks 52, 104 and 156 Week 156	0.38857 ratio Standard Deviation 0.475259	-0.02390 ratio Standard Deviation 0.860703	0.21449 ratio Standard Deviation 0.281091

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 52, 104 and 156

The efficacy of gantenerumab in reducing disease progression was assessed by CSF pTau-181. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=17 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=20 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=21 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in Phosphorylated Tau (pTau)-181 in Cerebrospinal Fluid (CSF) at Weeks 52, 104 and 156 Week 52	-3.29012 picogram per milliliter (pg/mL) Standard Deviation 3.301052	-2.95397 picogram per milliliter (pg/mL) Standard Deviation 3.225444	-0.28807 picogram per milliliter (pg/mL) Standard Deviation 1.740518
Change From Baseline in Phosphorylated Tau (pTau)-181 in Cerebrospinal Fluid (CSF) at Weeks 52, 104 and 156 Week 104	-7.15305 picogram per milliliter (pg/mL) Standard Deviation 5.152265	-6.03388 picogram per milliliter (pg/mL) Standard Deviation 4.745042	-1.19673 picogram per milliliter (pg/mL) Standard Deviation 2.262092
Change From Baseline in Phosphorylated Tau (pTau)-181 in Cerebrospinal Fluid (CSF) at Weeks 52, 104 and 156 Week 156	-8.13416 picogram per milliliter (pg/mL) Standard Deviation 5.861080	-6.83542 picogram per milliliter (pg/mL) Standard Deviation 3.548298	-1.48436 picogram per milliliter (pg/mL) Standard Deviation 2.746503

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 52, 104 and 156

The efficacy of gantenerumab in reducing disease progression was assessed by CSF NfL. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=16 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=20 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=21 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in Neurofilament Light Chain (NfL) in Cerebrospinal Fluid at Weeks 52, 104 and 156 Week 52	176.01 pg/mL Standard Deviation 223.432	283.97 pg/mL Standard Deviation 255.009	106.09 pg/mL Standard Deviation 252.328
Change From Baseline in Neurofilament Light Chain (NfL) in Cerebrospinal Fluid at Weeks 52, 104 and 156 Week 104	263.74 pg/mL Standard Deviation 268.343	351.02 pg/mL Standard Deviation 312.203	257.12 pg/mL Standard Deviation 255.528
Change From Baseline in Neurofilament Light Chain (NfL) in Cerebrospinal Fluid at Weeks 52, 104 and 156 Week 156	233.30 pg/mL Standard Deviation 186.805	609.45 pg/mL Standard Deviation 549.253	402.20 pg/mL Standard Deviation 536.504

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 52, 104 and 156

The efficacy of gantenerumab in reducing disease progression was assessed by CSF Amyloid Beta1-42/40. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=17 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=20 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=21 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in Amyloid Beta1-42/40 Ratio in Cerebrospinal Fluid at Weeks 52, 104 and 156 Week 52	0.00669 ratio Standard Deviation 0.015517	0.01217 ratio Standard Deviation 0.013657	-0.00060 ratio Standard Deviation 0.008280
Change From Baseline in Amyloid Beta1-42/40 Ratio in Cerebrospinal Fluid at Weeks 52, 104 and 156 Week 104	0.02961 ratio Standard Deviation 0.022677	0.03588 ratio Standard Deviation 0.025329	0.00571 ratio Standard Deviation 0.010013
Change From Baseline in Amyloid Beta1-42/40 Ratio in Cerebrospinal Fluid at Weeks 52, 104 and 156 Week 156	0.04400 ratio Standard Deviation 0.024807	0.05304 ratio Standard Deviation 0.037927	0.01182 ratio Standard Deviation 0.022581

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 52, 104 and 156

The efficacy of gantenerumab in reducing disease progression was assessed by DIAN-TU OLE Cognitive Composite. The cognitive composite was calculated based on the below 4 components, 1. The wechsler adult intelligence scale-revised digit span (backward recall). Score ranges from 0 (minimum) to 7 (maximum). 2. The category fluency (animals) value. Score ranges from 0 to unlimited. 3. The wechsler adult intelligence scale digit symbol substitution test. Score ranges from 0 (minimum) to 93 (maximum). 4. The MMSE. Score ranges from 0 (minimum) to 30 (maximum). Lower scores of each component indicate worse performance. The cognitive composite is a normalized z score and has score range - 4.11 to unlimited as one of the components has score range 0 to unlimited. Lower score indicates worse performance. Baseline was defined as last non-missing measurement prior to OLE study drug administration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo - OLE Gantenerumab n=17 Participants Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=22 Participants Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=23 Participants Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
Change From Baseline in DIAN-TU Open Label Extension Cognitive Composite Score at Weeks 52, 104 and 156 Week 52	-0.2281 score on a scale Standard Deviation 0.44682	-0.1462 score on a scale Standard Deviation 0.37510	-0.1336 score on a scale Standard Deviation 0.26523
Change From Baseline in DIAN-TU Open Label Extension Cognitive Composite Score at Weeks 52, 104 and 156 Week 104	-0.5535 score on a scale Standard Deviation 0.82376	-0.2373 score on a scale Standard Deviation 0.49333	-0.2493 score on a scale Standard Deviation 0.48045
Change From Baseline in DIAN-TU Open Label Extension Cognitive Composite Score at Weeks 52, 104 and 156 Week 156	-0.3309 score on a scale Standard Deviation 0.60877	-0.2738 score on a scale Standard Deviation 0.49439	-0.1327 score on a scale Standard Deviation 0.31666

Adverse Events

Double-blind Placebo - OLE Gantenerumab

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Double-blind Solanezumab - OLE Gantenerumab

Serious events: 4 serious events

Other events: 27 other events

Deaths: 0 deaths

Double-blind Gantenerumab - OLE Gantenerumab

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-blind Placebo - OLE Gantenerumab n=18 participants at risk Eligible participants from placebo treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Solanezumab - OLE Gantenerumab n=27 participants at risk Eligible participants from solanezumab treatment group in double-blind period entered OLE period to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.	Double-blind Gantenerumab - OLE Gantenerumab n=28 participants at risk Eligible participants from gantenerumab treatment group in double-blind period entered OLE period to continue to receive gantenerumab up to 1500 mg SC infusion Q2W for 3 years.
General disorders Non-cardiac chest pain	0.00% 0/18 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/27 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Hepatobiliary disorders Cholecystitis	0.00% 0/18 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/27 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Infections and infestations Diverticulitis	5.6% 1/18 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/27 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/28 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Infections and infestations Metapneumovirus bronchiolitis	0.00% 0/18 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/27 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/18 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/27 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/18 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.7% 1/27 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/28 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/18 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.7% 1/27 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/28 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Nervous system disorders Amyloid related imaging abnormality-oedema/effusion	5.6% 1/18 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.7% 1/27 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/28 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Nervous system disorders Epilepsy	0.00% 0/18 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.7% 1/27 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/28 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Nervous system disorders Vertebral artery occlusion	0.00% 0/18 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/27 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.
Psychiatric disorders Psychotic behaviour	0.00% 0/18 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	3.7% 1/27 • Number of events 1 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.	0.00% 0/28 • Treatment-emergent adverse events are reported from the first dose administration of the OLE study drug (Day 1) up to early termination of study, approximately 156 weeks. The safety analysis population included all participants who received at least 1 dose of study drug in the gantenerumab OLE period. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.

Other adverse events

Additional Information

Administrative Director

Washington University

Phone: (314) 221-8344

Email: [email protected]

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