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

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ClinicalTrials.gov Identifier: NCT02353598
Recruitment Status : Completed
First Posted : February 3, 2015
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE January 23, 2015
First Posted Date  ICMJE February 3, 2015
Last Update Posted Date July 24, 2019
Actual Study Start Date  ICMJE February 26, 2015
Actual Primary Completion Date November 30, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2016)
  • Number of participants with anti-crenezumab antibodies [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: From baseline up to follow-up period (Week 69) ]
  • Number of participants with amyloid-related imaging abnormalities-hemorrhage (ARIA-H) [ Time Frame: 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) [ Time Frame: From baseline up to follow-up period (Week 69) ]
  • Number of participants with of non-serious AEs of special interest [ Time Frame: From baseline up to follow-up period (Week 69) ]
  • Number of participants with amyloid-related imaging abnormalities-edema/effusion (ARIA-E) [ Time Frame: Up to Week 13 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 30, 2015)
  • Incidence and nature of adverse events (AEs) [ Time Frame: Up to 13 weeks ]
  • Changes in vital signs/physical findings [ Time Frame: From baseline to end-of-treatment, approximately 10 months ]
  • Incidence of anti-crenezumab antibodies [ Time Frame: Up to 10 months ]
  • Frequency of non-serious adverse events of special interest [ Time Frame: Up to 10 months ]
  • Changes in clinical laboratory results [ Time Frame: From baseline to end-of-treatment, approximately 10 months ]
  • Changes in ECGs [ Time Frame: From baseline to end-of-treatment, approximately 10 months ]
  • Incidence and nature of MRI safety findings (ARIA-E and ARIA-H) [ Time Frame: Up to 13 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2016)
Serum concentration of crenezumab [ Time Frame: 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2015)
Serum crenezumab concentrations at protocol-specified timepoints [ Time Frame: Up to 13 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Crenezumab in Participants With Mild to Moderate Alzheimer Disease
Official Title  ICMJE A Phase Ib, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel-Arm, Multiple-Dose Study to Assess The Safety, Tolerability, And Pharmacokinetics of Intravenous Crenezumab Administered in Patients With Mild to Moderate Alzheimer's Disease
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE
  • Drug: Crenezumab dose level 1
    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.
  • Drug: Crenezumab dose level 2
    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.
  • Drug: Crenezumb dose level 3
    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.
  • Drug: Placebo
    Participants will receive placebo matched to crenezumab IV infusion once every 4 weeks upto Week 13 in double-blind treatment window.
Study Arms  ICMJE
  • Experimental: Double-blind treatment window: Crenezumab dose level 1
    Participants will recieve crenezumab dose level 1 once every 4 weeks.
    Intervention: Drug: Crenezumab dose level 1
  • Experimental: Double-blind treatment window: Crenezumab dose level 2
    Participants will receive crenezumab dose level 2 once every 4 weeks.
    Intervention: Drug: Crenezumab dose level 2
  • Experimental: Double-blind treatment window: Crenezumab dose level 3
    Participants will receive crenezumab dose level 3 once every 4 weeks.
    Intervention: Drug: Crenezumb dose level 3
  • Placebo Comparator: Double-blind treatment window: Placebo
    Participants will receive placebo matched to crenezumab once every 4 weeks.
    Intervention: Drug: Placebo
  • Experimental: Optional OLE window: Crenezumab
    Participants will receive crenezumab dose levels 1 2, or 3 once in every 4 weeks.
    Interventions:
    • Drug: Crenezumab dose level 1
    • Drug: Crenezumab dose level 2
    • Drug: Crenezumb dose level 3
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 24, 2017)
77
Original Estimated Enrollment  ICMJE
 (submitted: January 30, 2015)
24
Actual Study Completion Date  ICMJE March 26, 2019
Actual Primary Completion Date November 30, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • History of malignancies within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer; cancer that is considered likely to be cured, is not being actively treated with anti-cancer therapy or radiotherapy and not likely to require treatment in the ensuing 5 years as well as cancers that are considered to have low probability of recurrence are allowed
  • Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
  • Severe or unstable medical condition that, in the opinion of the investigator or sponsor, could be expected to progress, recur, or change to such an extent that it could put the patient at special risk, bias the assessment of the clinical or mental status of the patient to a significant degree, interfere with the patient's ability to complete the study assessments, or would require the equivalent of institutional or hospital care
  • Any previous treatment with medications used to treat Parkinsonian symptoms or any other neurodegenerative disorder within 1 year before screening even if the patient is taking the medicine for a non-neurodegenerative disorder such as restless leg disorder
  • Typical anti-psychotic or neuroleptic medication within 6 months before screening except as brief treatment for a non-psychiatric indication
  • Antihemostasis medication within 2 weeks before screening
  • Sedative, hypnotic, or benzodiazepine medication within 3 months before screening except intermittent use of the following for sleep or anxiety: alprazolam, lorazepam, oxazepam, temazepam, diazepam, or a short-acting benzodiazepine-like medication
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02353598
Other Study ID Numbers  ICMJE GN29632
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Genentech, Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP