Phase 3 N=262 Randomized Quadruple-blind Treatment

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.

Alzheimers Disease · Dementia · Alzheimers Disease, Familial

Bottom Line

View on ClinicalTrials.gov: NCT04623242 ↗

Enrolled (actual)

262

Serious AEs

17.9%

Results posted

Sep 2022

Primary outcome: Primary: Assess Cognitive Efficacy in Individuals With Mutations Causing Dominantly Inherited AD as Measured by the DIAN-Multivariate Cognitive Endpoint (DIAN-MCE); — 1.063; 1.255 Ratio

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Gantenerumab (Drug); Solanezumab (Drug); Matching Placebo (Gantenerumab) (Drug); Matching Placebo (Solanezumab) (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Washington University School of Medicine
Primary completion: Nov 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Assess Cognitive Efficacy in Individuals With Mutations Causing Dominantly Inherited AD as Measured by the DIAN-Multivariate Cognitive Endpoint (DIAN-MCE);	1.063; 1.255	—
SECONDARY Gantenerumab: Rate of Change Over Time- Clinical Dementia Rating Sum of Boxes (CDR-SB)	0.74; 0.44; 1.27; 1.36; 1.95; 2.28	0.805
SECONDARY Gantenerumab: Rate of Change Over Time- Functional Assessment Scale (FAS)	1.23; 1.40; 2.34; 2.44; 3.45; 4.07	0.512
SECONDARY Gantenerumab: Imaging Measures Composite [11C] PiB Partial Volume Corrected Regional Spread Function Standardized Uptake Value Ratio - Composite	-0.006; 0.103; -0.106; 0.134; -0.334; 0.306	<0.001 sig
SECONDARY Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR)	11; 8; 38; 32; 18; 8	0.5573
SECONDARY Solanezumab: Clinical Measures- CDR Sum of Boxes (CDR-SB)	0.90; 0.44; 1.87; 1.36; 2.55; 2.28	0.707
SECONDARY Solanezumab: Clinical Measures- Geriatric Depression Scale (GDS)	0.20; -0.14; 0.06; 0.03; -0.22; -0.07	0.283
SECONDARY Solanezumab: Clinical Measures- Neuropsychiatric Inventory Questionnaire (NPI-Q)	0.49; 1.06; 0.70; 1.54; 1.31; 1.10	0.674
SECONDARY Solanezumab: Clinical Measures- Functional Assessment Scale (FAS)	0.68; 1.40; 2.21; 2.44; 3.03; 4.07	0.507
SECONDARY Solanezumab: Clinical Measures- Mini-Mental Status State Examination (MMSE)	-1.30; -0.83; -2.59; -1.73; -3.76; -3.23	0.553
SECONDARY Solanezumab: Cognitive Measures- International Shopping List Task 30-Minute Delayed Recall	-0.35; -0.17; -0.98; -0.64; -1.55; -0.42	0.098
SECONDARY Solanezumab: Cognitive Measures- Groton Maze Learning Test 30 Minute Delayed Recall	1.00; -0.13; 1.16; 0.78; 2.40; 0.96	0.173
SECONDARY Solanezumab: Cognitive Measures- Groton Maze Learning Test Delayed Reversed Recall	7.08; -1.34; 6.21; 3.28; 6.45; 1.82	0.940
SECONDARY Solanezumab: Cognitive Measures- Trailmaking Test Part A	9.73; 5.14; 15.03; 11.38; 19.45; 15.21	0.854
SECONDARY Solanezumab: Cognitive Measures- Trailmaking Test Part B	-2.39; 8.00; -0.20; 10.52; 21.59; 21.35	0.781
SECONDARY Solanezumab: Cognitive Measures- WAIS-R Digit-Symbol Substitution Test	0.35; -1.02; -0.97; 0.20; -3.64; -1.72	0.689
SECONDARY Solanezumab: Cognitive Measures- WMS-R Digit Span Backward	0.06; -0.12; -0.41; -0.16; -1.14; -0.28	0.474
SECONDARY Solanezumab: Cognitive Measures- WMS-R Digit Span Forward	-0.76; -0.38; -1.03; -0.84; -1.50; -1.23	0.886
SECONDARY Solanezumab: Cognitive Measures- Raven's Progressive Matrices (Set A)	-0.47; -0.70; -0.93; -0.63; -1.38; -1.06	0.873
SECONDARY Solanezumab: Cognitive Measures- Category Fluency (Animals)	-1.86; -2.19; -1.64; -2.50; -2.84; -2.46	0.394
SECONDARY Solanezumab: Cognitive Measures- Category Fluency (Vegetables)	-0.83; -1.41; -1.22; -1.74; -1.29; -1.43	0.776
SECONDARY Solanezumab: Cognitive Measures- WMS-R Logical Memory Delayed Recall Test	0.64; 1.33; 1.25; 1.71; 1.21; 2.37	0.283
SECONDARY Solanezumab: Cognitive Measures- WMS-R Logical Memory Immediate Recall Test	0.40; -0.06; 0.73; 0.75; 0.13; 0.91	0.634
SECONDARY 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	—
SECONDARY Solanezumab: Imaging Measures- Brain Amyloid Load as Measured by [11C]PiB-PET Non-partial Volume Corrected	0.030; 0.025; 0.019; 0.022; 0.113; 0.093	0.726
SECONDARY Solanezumab: Imaging Measures- Brain Amyloid Load as Measured by Florbetapir PET	0.066; 0.105; 0.251; 0.168	0.439
SECONDARY Solanezumab: Imaging Measures- Brain Glucose Metabolism as Measured by Fluorodeoxyglucose (FDG)-PET Non-partial Volume Corrected	-0.021; -0.030; -0.047; -0.043; -0.074; -0.074	0.967
SECONDARY Solanezumab: Imaging Measures- Brain Atrophy as Measured by Cortical Thickness of Regions of Interest - Precuneus Region	-0.033; -0.053; -0.067; -0.090; -0.110; -0.122	0.669
SECONDARY Solanezumab: Imaging Measures- Volumetric MRI Combined Total Volume Corrected for Head Size - Hippocampus Volume	-106.74; -153.34; -341.35; -302.58; -524.14; -541.76	0.768
SECONDARY Solanezumab: Imaging Measures- Brain Tau Load as Measured by Flortaucipir PET Non-partial Volume Corrected	1.77391; 1.52502; 1.46020; 1.49041; 0.11302; -0.03925	—
SECONDARY Solanezumab: Imaging Measures- Brain Atrophy as Measured by Whole Brain Volume Corrected for Head Size	-11990.31; -10578.56; -19808.05; -22147.27; -32713.22; -30590.95	0.677
SECONDARY Solanezumab: Imaging Measures- Brain Atrophy as Measured by Ventricular Volume (Volumetric MRI) Corrected for Head Size	1815.99; 1796.78; 2972.85; 4452.69; 5705.59; 6729.64	0.547
SECONDARY Solanezumab: Fluid Biomarker Measures- CSF Aβ 40 Free Change From Baseline	-1613.48; -856.65; -2237.73; -1398.13; -2567.13; -631.22	<0.001 sig
SECONDARY Solanezumab: Fluid Biomarker Measures- CSF Aβ 42 Free	-109.33; -79.35; -172.55; -125.64; -250.78; -173.66	0.003 sig
SECONDARY Solanezumab: Fluid Biomarker Measures- CSF Tau	4.73; -6.60; 31.74; 23.24; 59.08; 28.19	0.388
SECONDARY Solanezumab: Fluid Biomarker Measures- CSF pTau 181	0.26; -0.18; 4.91; 4.25; 6.90; 7.65	0.909
SECONDARY Solanezumab: Change From Baseline Fluid Biomarker Measures- CSF Neurofilament Light Chain (NfL)	0.102; 0.144; 0.191; 0.159; 0.426; 0.248	0.004 sig
SECONDARY Solanezumab: Fluid Biomarker Measures- Plasma Neurofilament Light Chain (NfL)	0.47; 4.03; 1.22; 3.15; 3.29; 3.72	0.754
SECONDARY Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug Antibodies (ADA)	43; 22; 3; 3; 2; 3	—
SECONDARY Solanezumab: Fluid Biomarker Measures- Total Plasma Aβ 1-40	168588.48; -9257.53; 165220.34; -9263.35; 220136.05; -9226.25	<0.001 sig
SECONDARY Solanezumab: Fluid Biomarker Measures- Total Plasma Aβ 42	30609.39; 526.91; 29265.35; 746.90; 33744.89; 838.29	<0.001 sig
SECONDARY Solanezumab: Fluid Biomarker Measures- CSF Aβ 42 Total	558.91; 44.81; 623.16; 89.32; 1352.83; 66.48	<0.001 sig
SECONDARY Solanezumab: Fluid Biomarker Measures- CSF Aβ 40 Total	3676.97; -414.57; 4017.93; -594.08; 9723.95; -143.31	<0.001 sig

Summary

The purpose of this study is to assess the safety, tolerability, biomarker and cognitive efficacy of investigational products in subjects who are known to have an Alzheimer's disease-causing mutation by determining if treatment with the study drug slows the rate of progression of cognitive impairment and improves disease-related biomarkers. This is an analysis study for an MPRP: DIAN-TU-001 Master NCT01760005

Eligibility Criteria

Inclusion Criteria

Between 18-80 years of age
Individuals who know they have an Alzheimer's disease-causing mutation or are unaware of their genetic status and have dominantly inherited Alzheimer's disease (DIAD) mutation in their family.
Are within -15 to + 10 years of the predicted or actual age of cognitive symptom onset.
Cognitively normal or with mild cognitive impairment or mild dementia, Clinical Dementia Rating (CDR) of 0-1 (inclusive)
Fluency in DIAN-TU trial approved language and evidence of adequate premorbid intellectual functioning
Able to undergo Magnetic Resonance Imaging (MRI), Lumbar Puncture (LP), Positron Emission Tomography (PET), and complete all study related testing and evaluations.
For women of childbearing potential, if partner is not sterilized, subject must agree to use effective contraceptive measures (hormonal contraception, intra-uterine device, sexual abstinence, barrier method with spermicide).
Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments.
Has a Study Partner who in the investigator's judgment is able to provide accurate information as to the subject's cognitive and functional abilities, who agrees to provide information at the study visits which require informant input for scale completion.

Exclusion Criteria

History or presence of brain MRI scans indicative of any other significant abnormality
Alcohol or drug dependence currently or within the past 1 year
Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin or body which would preclude MRI scan.
History or presence of clinically significant cardiovascular disease, hepatic/renal disorders, infectious disease or immune disorder, or metabolic/endocrine disorders
Anticoagulants except low dose (≤ 325 mg) aspirin.
Have been exposed to a monoclonal antibody targeting beta amyloid peptide within the past six months.
History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years.
Positive urine or serum pregnancy test or plans or desires to become pregnant during the course of the trial.
Subjects unable to complete all study related testing, including implanted metal that cannot be removed for MRI scanning, required anticoagulation and pregnancy.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04623242). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.