Phase 2 N=272 Randomized Quadruple-blind Treatment

A Study of Semorinemab in Patients With Moderate Alzheimer's Disease

Alzheimer's Disease

Bottom Line

View on ClinicalTrials.gov: NCT03828747 ↗

Enrolled (actual)

272

Serious AEs

17.6%

Results posted

Oct 2022

Primary outcome: Primary: Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) — 23.93; 24.09; 3.96; 6.85 Units on a scale — p=0.0008

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Semorinemab (Drug); Placebo (Drug); [18F]GTP1 (Drug)
Age: Adult, Older Adult · 50+ yrs
Sex: All
Sponsor: Genentech, Inc.
Primary completion: Jul 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)	23.93; 24.09; 3.96; 6.85; 5.71; 8.47	0.0008 sig
PRIMARY Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)	62.03; 59.74; -7.63; -6.80; -9.29; -7.57	0.5207
SECONDARY Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)	6.23; 6.51; 1.80; 1.54; 2.45; 2.28	0.3501
SECONDARY Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)	18.38; 18.15; -2.86; -3.12; -3.14; -4.22	0.5366
SECONDARY Percentage of Participants With Adverse Events	112; 107; 170	—
SECONDARY Serum Concentration of RO7105705 at Specified Timepoints	NA; 1610; 546; 1980; 951; 2260	—
SECONDARY Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline	0; 1; 133; 128; 0; 128	—
SECONDARY Relationship Between ADA Status and Percentage of Participants With Adverse Events	NA; NA	—
SECONDARY Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)	NA; NA	—
SECONDARY Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)	NA; NA	—
SECONDARY Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)	NA; NA	—
SECONDARY Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)	NA; NA	—
SECONDARY Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints	NA; NA	—
SECONDARY Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline	0; 1; NA; NA	—

Summary

This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in patients with moderate AD. The study consists of a screening period, a double-blind treatment period, an optional open-label extension (OLE) period, and a safety follow-up period. There may be up to two study cohorts.

Eligibility Criteria

Inclusion Criteria

National Institute on Aging/Alzheimer's Association core clinical criteria for probable AD dementia
Evidence of the AD pathological process, by a positive amyloid assessment either on CSF Aβ1-42 as measured on Elecsys β-Amyloid(1-42) Test System OR amyloid PET scan
AD dementia of moderate severity, as defined by a screening MMSE score of 16-21 points, inclusive, and a CDR-GS of 1 or 2
Availability of a person with sufficient contact with the participant to be able to provide accurate information on the participant's cognitive, behavioral and functional ability

Exclusion Criteria

Pregnant or breastfeeding
Inability to tolerate MRI procedures or contraindication to MRI
Contraindication to PET imaging
Residence in a skilled nursing facility
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or bias the assessment of the clinical or mental status of the participant to a significant degree
Any evidence of a condition other than AD that may affect cognition
Substance abuse within the past 2 years
Use of any experimental therapy within 90 days or 5 half-lives prior to screening, whichever is greater, or any passive immunotherapy against tau
Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was at least 1 year prior to screening or any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline
Any other biologic therapy or previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other non-AD neurodegenerative disorder within 1 year of screening
Systemic immunosuppressive therapy within 12 months of screening through the entire study period
Typical antipsychotic or neuroleptic medication within 6 months of screening
Daily treatment with any of the following classes of medication (except for intermittent short-term use): opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally-acting antihistamine or anticholinergic activity
Stimulant medications, unless the dose has been stable within the 6 months prior to screening and is expected to be stable throughout the study

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03828747). 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.