A Study of Crenezumab Versus Placebo in Preclinical PSEN1 E280A Mutation Carriers to Evaluate Efficacy and Safety in the Treatment of Autosomal-Dominant Alzheimer Disease, Including a Placebo-Treated Noncarrier Cohort.

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Genentech, Inc.
Sponsor:
Collaborator:
Banner Alzheimer's Institute
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01998841
First received: November 22, 2013
Last updated: October 6, 2014
Last verified: October 2014
  Purpose

This randomized, double-blind, placebo-controlled, parallel group, adaptive stu dy will evaluate the efficacy and safety of crenezumab versus placebo in individ uals who carry the PSEN1 E280A autosomal-dominant mutation and do not meet the criteria for mild cognitive impairment due to Alzheimer disease or dementia due to Alzheimer disease and are, thus, in a preclinical phase of Alzheimer disease.

Patients will be randomized 1 : 1 to receive either crenezumab or placebo subcu taneously every 2 weeks for 260 weeks. The study also includes a cohort of PSEN1 E280A mutation noncarriers who will be dosed with placebo only.


Condition Intervention Phase
Alzheimer Disease
Drug: crenezumab
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A DOUBLE-BLIND, PLACEBO-CONTROLLED PARALLEL-GROUP STUDY IN PRECLINICAL PSEN1 E280A MUTATION CARRIERS RANDOMIZED TO CRENEZUMAB OR PLACEBO, AND IN NONRANDOMIZED, PLACEBO-TREATED NONCARRIERS FROM THE SAME KINDRED, TO EVALUATE THE EFFICACY AND SAFETY OF CRENEZUMAB IN THE TREATMENT OF AUTOSOMAL-DOMINANT ALZHEIMER'S DISEASE

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Change on Alzheimer's Prevention Initiative (API) Composite Cognitive Test total score (including Word List: Recall, Multilingual Naming Test, MMSE, CERAD Constructional Praxis, Raven's Progressive Matrices) [ Time Frame: from baseline to Week 260 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety: Incidence of adverse events [ Time Frame: 260 weeks ] [ Designated as safety issue: No ]
  • Time to progression to mild cognitive impairment (MCI) due to AD or to dementia due to AD [ Time Frame: 260 weeks ] [ Designated as safety issue: No ]
  • Time to Clinical Dementia Rating (CDR) global score of > 0 [ Time Frame: 260 weeks ] [ Designated as safety issue: No ]
  • Change in CDR Scale-Sum of boxes [ Time Frame: from baseline to Week 260 ] [ Designated as safety issue: No ]
  • Change in episodic memory measure: Free and Cued Selective Reminding Task (FCSRT) [ Time Frame: from baseline to Week 260 ] [ Designated as safety issue: No ]
  • Change in measure of overall neurocognitive functioning: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: from baseline to Week 260 ] [ Designated as safety issue: No ]
  • Change in mean cerebral fibrillar amyloid accumulation [ Time Frame: from baseline to Week 260 ] [ Designated as safety issue: No ]
  • Change in regional cerebral metabolic rate of glucose (CMRrI) [ Time Frame: from baseline to Week 260 ] [ Designated as safety issue: No ]
  • Change in brain atrophy measured by volumetric measurements using MRI [ Time Frame: from baseline to Week 260 ] [ Designated as safety issue: No ]
  • Change in a tau-based cerebral spinal fluid biomarker [ Time Frame: from baseline to Week 260 ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: December 2013
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mutation Carriers: Crenezumab Drug: crenezumab
SC every 2 weeks
Placebo Comparator: Mutation Carriers: Placebo Drug: placebo
SC every 2 weeks
Placebo Comparator: Noncarriers of Mutation: Placebo Drug: placebo
SC every 2 weeks

  Eligibility

Ages Eligible for Study:   30 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >/= 30 and </= 60 years of age
  • Membership in PSEN1 E280A mutation carrier kindred
  • Agrees to conditions of, and is willing to undergo, genetic testing (e.g., APOE, PSEN1 E280A, and other genetic testing)
  • PSEN1 E280A mutation carrier or noncarrier status has been confirmed prior to or during the screening period
  • MMSE >/= 26
  • Does not meet criteria for dementia due to AD (McKhann 2011)
  • Does not meet criteria for MCI due to AD (Albert 2011)
  • Adequate vision and hearing in the investigator's judgment to be able to complete testing
  • Women of childbearing potential and men with partners of childbearing potential must agree to remain abstinent or use adequate methods of contraception as defined by protocol during the treatment period and for at least 16 weeks after the last dose of study drug
  • Study partner who agrees to participate in the study and is capable of and willing to accompany the participant to all visits requiring the following:

    • In-person attendance of the study partner
    • Information for required telephone assessments
    • Sufficient time with the participant to be familiar with his/her overall function and behavior
  • Participant and study partner have evidence of adequate premorbid functioning (e.g., intellectual, visual, and auditory)
  • Participant and study partner are fluent in, and able to read, the language in which study assessments are administered
  • Willing and able to undergo neuroimaging (PET and MRI)
  • Serum TSH and B12 within normal or expected range for the testing laboratory If participant is taking thyroid hormone, corresponding test values within the normal or expected ranges If participant is taking vitamin B12 injection, level at or above the lower limit of normal
  • Taking stable doses of all prescription (not including antidepressants) and nonprescription medications (including nutritional supplements) for the treatment of non-excluded medical condition(s) for at least 30 days prior to the screening visit.

Stable doses of antidepressants maintained for 6 weeks prior to the screening visit.

  • In good general health with no known co-morbidities expected to interfere with participation in the study

Exclusion Criteria:

  • Significant medical, psychiatric, or neurological condition or disorder documented by history, physical, neurological, laboratory, or ECG examination that would place the participant at undue risk in the investigator's judgment or impact the interpretation of efficacy
  • History of stroke Participants with a history of transient ischemic attack may be enrolled if the event occurred >/= 2 years prior to screening
  • History of severe, clinically significant (persistent neurological deficit or structural brain damage) central nervous system trauma (e.g. cerebral contusion)
  • Body weight <40 or >120 kg
  • History or presence of atrial fibrillation that poses a risk for future stroke in the investigator's judgment
  • Current presence of bipolar disorder or other clinically significant major psychiatric disorder according to DSM-IV-TR or symptom (e.g., hallucinations, agitation, paranoia) that could affect the participant's ability to complete evaluations
  • Geriatric Depression Scale (short form) (15-point scale) score > 9 at screening
  • History of seizures (excluding febrile seizures of childhood)
  • Myocardial infarction within 2 years, congestive heart failure, atrial fibrillation, or uncontrolled hypertension
  • Pregnant or nursing women, or women who intend to become pregnant or to nurse infants during the conduct of this trial
  • Clinically significant infection within the last 30 days prior to screening
  • Positive urine test for drugs of abuse at screening
  • History of alcohol or substance dependence within the previous two years
  • Use of any other medications with the potential to significantly affect cognition
  • Use of typical anti-psychotics, barbiturates, or anti-cholinergic antidepressants unless used in low doses for conditions other than depression, such as migraine headaches, and approved by the medical monitor
  • Use of non-anti-cholinergic antidepressant medications or atypical anti-psychotics unless maintained on a stable dose regimen for at least 6 weeks prior to screening
  • Use of any FDA/INVIMA-approved medications for treatment of LOAD at screening/baseline Cholinesterase inhibitors and/or memantine are prohibited during the study except in participants enrolled in the study that develop AD dementia.

Use of anti-coagulant medication, except aspirin (heparinoids, heparin, warfarin, thrombin inhibitors, Factor Xa inhibitors), or known coagulopathy or platelet count <100,000 cells/µL, within 4 weeks of the screening visit

  • Treatment with any biologic therapy within five half-lives or 3 months prior to screening, whichever is longer, with the exception of routinely recommended vaccinations, which are allowed
  • Use of anti-seizure medication (except in childhood for febrile seizures or if used for non-seizure indications), anti-parkinsonian, or stimulant (e.g., methylphenidate) medications
  • Use of investigational drug, device, or experimental medication within 60 days (or five half-lives, whichever is longer) of the screening visit
  • Previous treatment with crenezumab (MABT5102A) or any other therapeutic that targets A beta
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
  • Contraindication to MRI scan procedures or clinically significant claustrophobia that would contraindicate a brain MRI scan
  • Contraindication to PET scan procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01998841

Contacts
Contact: Reference Study ID Number: GN28352 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
Colombia
Recruiting
Medellin, Colombia
Recruiting
Yarumal, Colombia
Sponsors and Collaborators
Genentech, Inc.
Banner Alzheimer's Institute
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

No publications provided

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01998841     History of Changes
Other Study ID Numbers: GN28352
Study First Received: November 22, 2013
Last Updated: October 6, 2014
Health Authority: INVIMA: Instituto Nacional de Vigilancia de Medicamentos y Alimentos

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on October 21, 2014