Baseline characteristics for CLARITY AD: A phase 3 placebo‐controlled, double‐blind, parallel‐group, 18‐month study evaluating lecanemab (ban2401) in early Alzheimer's disease

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

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Acetyl L-Carnitine Slows Decline in Younger Patients With Alzheimer's Disease: A Reanalysis of a Double-Blind, Placebo-Controlled Study Using the Trilinear Approach

International Psychogeriatrics ◽

10.1017/s1041610298005304 ◽

1998 ◽

Vol 10 (2) ◽

pp. 193-203 ◽

Cited By ~ 33

Author(s):

John O. Brooks ◽

Jerome A. Yesavage ◽

Angelico Carta ◽

Daniele Bravi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Average Rate ◽

The United States ◽

Rate Of Change ◽

Disease Assessment ◽

Controlled Study ◽

Double Blind ◽

Parallel Group ◽

Longitudinal Effects

Objectives: To assess the longitudinal effects of acetyl-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease. Design: Longitudinal, double-blind, parallel-group, placebocontrolled. Setting: Twenty-four outpatient sites across the United States. Participants: A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996). Measurements: Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year. Results: The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age × Drug interaction characterized by younger subjects benefiting more from ALC treatment than older subjects. Further analyses suggested that the optimal, though not statistically significant, cutpoint for ALC benefit was 61 years of age. Conclusions: ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.

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Lecanemab, an anti-Aβ protofibril antibody: Updated data from a randomized, double-blind phase 2B proof of concept clinical trial and open-label extension in early Alzheimer's disease

Journal of the Neurological Sciences ◽

10.1016/j.jns.2021.117847 ◽

2021 ◽

Vol 429 ◽

pp. 117847

Author(s):

Chad Swanson ◽

Shobha Dhadda ◽

Mark Hodgkinson ◽

David Li ◽

Michio Kanekiyo ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trial ◽

Proof Of Concept ◽

Open Label ◽

Double Blind ◽

Open Label Extension ◽

Early Alzheimer’S Disease

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A Randomized, Controlled Trial of Linopirdine in the Treatment of Alzheimer's Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s031716710002148x ◽

1997 ◽

Vol 24 (2) ◽

pp. 140-145 ◽

Cited By ~ 31

Author(s):

Kenneth Rockwood ◽

B. Lynn Beattie ◽

M. Robin Eastwood ◽

Howard Feldman ◽

Erich Mohr ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Controlled Trial ◽

Small Degree ◽

Disease Assessment ◽

Double Blind ◽

Cognitive Subscale ◽

Parallel Group ◽

Treatment Dose ◽

Age Range

ABSTRACT:Objectives:We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease.Methods:A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline.Results:No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01.Conclusions:This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

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Emerge and Engage topline results: Phase 3 studies of aducanumab in early Alzheimer’s disease

Alzheimer s & Dementia ◽

10.1002/alz.047259 ◽

2020 ◽

Vol 16 (S9) ◽

Cited By ~ 1

Author(s):

Samantha Budd Haeberlein ◽

Christian von Hehn ◽

Ying Tian ◽

Spyros Chalkias ◽

Kumar Kandadi Muralidharan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Phase 3 ◽

Early Alzheimer’S Disease

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DGAVP (Org 5667) in early Alzheimer's disease patients: An international double-blind, placebo-controlled, multicenter trial

Neurology ◽

10.1212/wnl.40.7.1099 ◽

1990 ◽

Vol 40 (7) ◽

pp. 1099-1099 ◽

Cited By ~ 10

Author(s):

E. Ch. Wolters ◽

P. Riekkinen ◽

A. Lowenthal ◽

J. J. V. der Plaats ◽

J.M.T. Zwart ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Multicenter Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Early Alzheimer’S Disease

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A 36-week Multicenter, Randomised, Double-blind, Placebo-controlled, Parallel-group, Phase 3 Clinical Trial of Sodium Oligomannate for Mild-to-Moderate Alzheimer's Dementia

10.21203/rs.3.rs-108812/v1 ◽

2020 ◽

Author(s):

Shifu Xiao ◽

Piu Chan ◽

Tao Wang ◽

Zhen Hong ◽

Shuzhen Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trial ◽

Controlled Trial ◽

Drug Effects ◽

Disease Assessment ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo ◽

The Difference

Abstract Background: New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide which reconstitutes gut microbiota, reduces neuroinflammation, decreases amyloid deposition, and improves cognition in AD animal models. The first phase 3 clinical trial of GV-971 has been completed in China. Methods: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results: 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time-point, measurable at the week 4 visit and continuing throughout the trial. The difference between groups in change from baseline was −2.15 points (95% confidence interval, −3.07 to −1.23; P<0.0001; effect size 0.531) after 36 weeks treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group.Conclusions: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well tolerated. Trial registration: ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014.

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