A Study of Crenezumab in Participants With Mild to Moderate Alzheimer Disease

NCT02353598 | Completed Phase 1 FDA Drug

• 1 other identifier: GN29632
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 13

Brief Summary

This randomized, placebo-controlled, double-blind, parallel-arm study will evaluate the safety and tolerability of at least two dose levels of intravenous (IV) crenezumab in 24-72 participants with mild to moderate Alzheimer disease (AD) (mini-mental state examination \[MMSE\] 18 to 28 points, inclusive). An optional open-label extension (OLE) will be offered after the completion of initial double-blind stage.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (7)

• Number of participants with anti-crenezumab antibodies

  From baseline up to follow-up period (Week 69)

• Number of participants with suicidal ideation, suicidal behavior, and self-injurious behavior without suicidal intent, as determined using the columbia-cuicide severity rating scale (C-SSRS)

  From baseline up to follow-up period (Week 69)

• Number of participants with changes from baseline in vital signs, electrocardiogram (ECG) and clinical laboratory results

  From baseline up to follow-up period (Week 69)

• Number of participants with amyloid-related imaging abnormalities-hemorrhage (ARIA-H)

  Up to Week 13

• Number of participants with adverse events (AEs) and serious adverse events (SAEs) according to national cancer institute common terminology criteria for adverse events, version 4.0 (NCICTCAE v4.0)

  From baseline up to follow-up period (Week 69)

• Number of participants with of non-serious AEs of special interest

  From baseline up to follow-up period (Week 69)

• Number of participants with amyloid-related imaging abnormalities-edema/effusion (ARIA-E)

  Up to Week 13

Secondary Outcomes (1)

• Serum concentration of crenezumab

  Pre-dose on Day 1, 60-90 minutes (min) post infusion on Day 1, Days 2, 8, Week 2, pre-dose and 60-90 min post infusion on dosing day of Weeks 5, 9, 13, and 21; pre-dose and 60-90 min post infusion on dosing day of Weeks 25, 53, 61, and 69

Study Arms (5)

Double-blind treatment window: Crenezumab dose level 1

EXPERIMENTAL

Participants will recieve crenezumab dose level 1 once every 4 weeks.

Drug: Crenezumab dose level 1

Double-blind treatment window: Crenezumab dose level 2

EXPERIMENTAL

Participants will receive crenezumab dose level 2 once every 4 weeks.

Drug: Crenezumab dose level 2

Double-blind treatment window: Crenezumab dose level 3

EXPERIMENTAL

Participants will receive crenezumab dose level 3 once every 4 weeks.

Drug: Crenezumb dose level 3

Double-blind treatment window: Placebo

PLACEBO COMPARATOR

Participants will receive placebo matched to crenezumab once every 4 weeks.

Drug: Placebo

Optional OLE window: Crenezumab

EXPERIMENTAL

Participants will receive crenezumab dose levels 1 2, or 3 once in every 4 weeks.

Drug: Crenezumab dose level 1; Drug: Crenezumab dose level 2; Drug: Crenezumb dose level 3

Interventions

Crenezumab dose level 1 DRUG

Participants will receive crenezumb dose level 1 IV infusion once every 4 weeks up to Week 13 in double-blind treatment window or up to Week 61 in optional OLE window.

Double-blind treatment window: Crenezumab dose level 1; Optional OLE window: Crenezumab

Crenezumab dose level 2 DRUG

Participants will receive crenezumb dose level 2 IV infusion once every 4 weeks up to Week 13 in double-blind treatment window or up to Week 61 in optional OLE window.

Double-blind treatment window: Crenezumab dose level 2; Optional OLE window: Crenezumab

Crenezumb dose level 3 DRUG

Participants will receive crenezumb dose level 3 IV infusion once every 4 weeks upto Week 13 in double-blind treatment window or up to Week 61 in optional OLE window.

Double-blind treatment window: Crenezumab dose level 3; Optional OLE window: Crenezumab

Placebo DRUG

Participants will receive placebo matched to crenezumab IV infusion once every 4 weeks upto Week 13 in double-blind treatment window.

Double-blind treatment window: Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body weight greater than or equal (\>/=) 45 kilograms (kg) and less than or equal (\</=) 120 kg
• Ages 50-90 years, inclusive
• Availability of a person ("caregiver") who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits, which require partner input for scale completion, and signs the necessary consent form
• Willingness and ability to complete all aspects of the study; the participant should be capable of completing assessments either alone or with the help of the caregiver
• Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing
• Clinical diagnosis of probable mild to moderate AD based on the national institute on neurological and communication disease and stroke/Alzheimer's disease and related disorders association (NINCDS/ADRDA) criteria or probable major neurocognitive disorder due to AD of mild to moderate severity based on diagnostic and statistical manual of mental disorders, version 5 (DSM-5) criteria
• Screening MMSE score of 18-28 points, inclusive
• Screening clinical dementia rating global score (CDR-GS) of 0.5 or 1.0
• Screening geriatric depression (GDS)-15 score less than (\<) 6
• Positive florbetapir amyloid positron emission tomography (PET) scan by qualitative read conducted by the core/central PET laboratory
• Women must be postmenopausal or surgically sterile
• Men with female partners of childbearing potential agree to remain abstinent or use adequate methods of contraception as defined by protocol during the treatment period and for at least 8 weeks after the last dose of study drug and agreement to refrain from donating sperm during this same period

You may not qualify if:

• History or presence of clinically evident vascular disease potentially affecting the brain that, in the opinion of the investigator, has the potential to affect cognitive function
• History or presence of stroke within the previous 2 years or documented history of transient ischemic attack within the previous 12 months
• History of severe, clinically significant central nervous system trauma
• History or presence of intracranial tumor that is clinically relevant in the opinion of the investigator
• Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
• History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits
• History or presence of a neurologic disease other than AD that may affect cognition
• Presence of superficial siderosis, more than four cerebral microhemorrhages, or evidence of a prior cerebral macrohemorrhage
• Inability to tolerate magnetic resonance imaging (MRI) procedures or contraindication to MRI
• History or presence of atrial fibrillation except if only one episode that resolved more than 1 year ago and for which treatment is no longer indicated or that in the investigator's judgment poses no risk for future stroke
• Within the previous 2 years, unstable or clinically significant cardiovascular disease
• Uncontrolled hypertension
• Chronic kidney disease of Stage \>/= 4, according to the national kidney foundation kidney disease outcomes quality initiative (NKF KDOQI) guidelines for chronic kidney disease
• Impaired hepatic function
• Clinically significantly abnormal screening blood or urine that remain abnormal on retest

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (13)

Mayo Clinic Scottsdale

Phoenix, Arizona, 85054, United States

Location

UCSF - Memory and Aging Center

San Francisco, California, 94158, United States

Location

Brain Matters Research, Inc.

Delray Beach, Florida, 33445, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

Bioclinica Orlando

Orlando, Florida, 32806, United States

Location

Bioclinica The Villages

The Villages, Florida, 32162, United States

Location

Indiana University School Of Medicine; Department Of Neurology

Indianapolis, Indiana, 46202, United States

Location

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

Millennium Psychiatric Associates, LLC

St Louis, Missouri, 63132, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

UNiversity of Rochester

Rochester, New York, 14620, United States

Location

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, 02914, United States

Location

Roper St. Francis Healthcare; Clinical Biotechnology Research Institute

Charleston, South Carolina, 29401, United States

Location

Related Publications (2)

• Guthrie H, Honig LS, Lin H, Sink KM, Blondeau K, Quartino A, Dolton M, Carrasco-Triguero M, Lian Q, Bittner T, Clayton D, Smith J, Ostrowitzki S. Safety, Tolerability, and Pharmacokinetics of Crenezumab in Patients with Mild-to-Moderate Alzheimer's Disease Treated with Escalating Doses for up to 133 Weeks. J Alzheimers Dis. 2020;76(3):967-979. doi: 10.3233/JAD-200134.

  PMID: 32568196 DERIVED

• Yoshida K, Moein A, Bittner T, Ostrowitzki S, Lin H, Honigberg L, Jin JY, Quartino A. Pharmacokinetics and pharmacodynamic effect of crenezumab on plasma and cerebrospinal fluid beta-amyloid in patients with mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2020 Jan 22;12(1):16. doi: 10.1186/s13195-020-0580-2.

  PMID: 31969177 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: February 3, 2015
• Study Start: February 26, 2015
• Primary Completion: November 30, 2016
• Study Completion: March 26, 2019
• Last Updated: July 24, 2019

Record last verified: 2019-07

Locations

US (13)