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A Long-Term Safety Extension of Studies ABE4869g and ABE4955g in Participants With Mild to Moderate Alzheimer's Disease Treated With Crenezumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01723826
Recruitment Status : Completed
First Posted : November 8, 2012
Results First Posted : February 12, 2020
Last Update Posted : February 20, 2020
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE November 6, 2012
First Posted Date  ICMJE November 8, 2012
Results First Submitted Date  ICMJE January 24, 2020
Results First Posted Date  ICMJE February 12, 2020
Last Update Posted Date February 20, 2020
Actual Study Start Date  ICMJE December 7, 2012
Actual Primary Completion Date February 8, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to 50 months ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. . An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
  • Percentage of Participants by Nature of AEs [ Time Frame: Up to 50 months ]
    A serious adverse event (SAE) is any AE that meets any of the following criteria: fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect in a neonate/infant. Non-SAE of special interest for this study include the following: cerebral vascular edema, Superficial siderosis of central nervous system, cerebral micro-hemorrhages or macro-hemorrhages, pneumonia, liver injury.
  • Percentage of Participants by Severity of AEs [ Time Frame: Up to 50 months ]
    AE severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 was used for assessing adverse event severity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on the following general guideline: Grade 1) mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2) moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3) severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4) life-threatening consequences; urgent intervention indicated, Grade 5) death related to AE.
  • Percentage of Participants With Human Anti-Therapeutic Antibody (ATA) Formation [ Time Frame: Pre-dose (Day-14), predose at Week 25, 49, 97, Follow-up Week 8 (Week 153) and 12 (Week 157) ]
    ATA is a measurement to explore the potential relationship of immunogenicity response with pharmacokinetics, safety and efficacy. Percentage of participants at post-baseline with positive results for ATA against crenezumab are reported.
  • Percentage of Participants With Amyloid-Related Imaging Abnormalities Edema/Effusions (ARIA-E) [ Time Frame: Baseline, Weeks 23, 47, 71, 97, 121 and 153 ]
    Alzheimer's disease (AD) is associated with ARIA. The occurrence of imaging abnormalities believed to represent cerebral vasogenic edema, has been reported in association with the investigational use of compounds that are intended to treat Alzheimer's disease by reducing Abeta in the brain. Here, the percentage of participants with symptomatic and asymptomatic ARIA-E were reported.
  • Percentage of Participants With Amyloid-Related Imaging Abnormalities-Hemorrhage (ARIA-H) [ Time Frame: Baseline, Weeks 23, 47, 71, 97, 121 and 153 ]
    AD is associated with ARIA. Cerebral micro-hemorrhages (microbleeds [MBs]) are radiologically defined as small dot-like foci of signal loss observed on magnetic resonance imaging (MRI) sequences sensitive for paramagnetic tissue properties. The occurrence of MBs has also been identified as an adverse event in anti-amyloid vaccination trials, and together with superficial siderosis, they have been termed ARIA-H.
Original Primary Outcome Measures  ICMJE
 (submitted: November 6, 2012)
  • Frequency of adverse events during the treatment period [ Time Frame: 105 weeks ]
  • Nature and severity of adverse events during the treatment period [ Time Frame: 105 weeks ]
  • Changes in vital signs/physical findings [ Time Frame: from baseline to Week 105 ]
  • Changes in neurological findings [ Time Frame: from baseline to Week 105 ]
  • Changes in laboratory test results [ Time Frame: from baseline to Week 105 ]
  • Incidence of human anti-therapeutic antibody (ATA) formation [ Time Frame: 105 weeks ]
  • Incidence of ARIA-E and amyloid-related imaging abnormalities-hemorrhage (ARIA-H) [ Time Frame: 105 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Long-Term Safety Extension of Studies ABE4869g and ABE4955g in Participants With Mild to Moderate Alzheimer's Disease Treated With Crenezumab
Official Title  ICMJE A Multicenter, Open-Label, Long-Term Safety Extension of Phase II Studies ABE4869g and ABE4955g in Patients With Mild to Moderate Alzheimer's Disease
Brief Summary This Phase II, open-label extension (OLE), multicenter study will evaluate the long-term safety and tolerability of crenezumab in participants with mild to moderate Alzheimer's disease who have participated in and completed the treatment period of the Phase II Study ABE4869g (NCT01343966) or ABE4955g (NCT01397578). Participants who received placebo in Study ABE4869g (NCT01343966) or ABE4955g (NCT01397578) will receive crenezumab. Anticipated time on study treatment is 144 weeks.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE Drug: Crenezumab
Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
Other Name: RO5490245
Study Arms  ICMJE Experimental: Crenezumab
Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
Intervention: Drug: Crenezumab
Publications * Not Provided

*   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: December 1, 2015)
360
Original Estimated Enrollment  ICMJE
 (submitted: November 6, 2012)
400
Actual Study Completion Date  ICMJE February 8, 2017
Actual Primary Completion Date February 8, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Previous participation in Study ABE4869g or ABE4955g and completion of the Week 73 visit
  • Adequate visual and auditory acuity, in the investigator's judgment, to allow for neuropsychological testing
  • Availability of a person ("caregiver") who can provide information on activities of daily living and behavior in order to complete the study-specific assessments
  • Diagnosis of probable Alzheimer's disease according to the National Institute on Neurological and Communication Disease and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria (McKhann et al. 1984)
  • Mini-Mental State Examination (MMSE) score of 10 or more at screening (Folstein et al. 1975)
  • For male participants with partners with reproductive potential, agreement to use a reliable means of contraception (e.g., condoms) during the study and for at least 8 weeks following the last dose of study drug
  • For female participants, a negative pregnancy test at screening

Exclusion Criteria:

  • Early treatment and/or study discontinuation prior to completion of the Week 73 visit of Genentech Study ABE4869g or ABE4955g
  • Early discontinuation from the treatment schedule of a prior version of Study GN28525 for safety reasons. If treatment discontinuation occurred for safety reasons, participants may not re-start dosing on extended treatment schedules offered in amendments to Study GN28525
  • Inability to tolerate Magnetic Resonance Imaging (MRI) procedures or contraindication to MRI
  • Female participants with reproductive potential: Female participants must either have undergone documented surgical sterilization or have not experienced menstruation for at least 12 consecutive months
  • Severe or unstable medical condition that, in the opinion of the investigator or Sponsor, would interfere with the participant's ability to complete the study assessments or would require the equivalent of institutional or hospital care
  • History or presence of clinically evident vascular disease potentially affecting the brain
  • History of severe, clinically significant central nervous system trauma
  • History or presence of clinically relevant intracranial tumor
  • Presence of infections that affect the brain function or history of infections that resulted in neurologic sequelae
  • History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease
  • History or presence of a neurologic disease other than Alzheimer's disease that may affect cognition
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
  • Evidence of malignancies (except squamous cell cancer or basal cell cancer of the skin), acute infections, renal failure that requires dialysis, or other unstable medical disease not related to Alzheimer's disease that, in the investigator's opinion, would preclude participant's participation. Cancer that is not being actively treated with anti-cancer therapy or radiotherapy as well as cancers which are considered to have low probability of recurrence are allowed
  • History or presence of atrial fibrillation that, in the investigator's judgment, poses a risk for future stroke
  • Chronic kidney disease of Stage greater than or equal to (>=) 4, according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines for chronic kidney disease (CKD)
  • Impaired hepatic function
  • Impaired coagulation (activated partial thromboplastin time [aPTT] greater than [>] 1.2 times upper limit of normal [ULN])
  • Platelet count less than (<) 100,000 per microliter (mcL)
  • Presence at screening of superficial siderosis of central nervous system, more than 8 cerebral microhemorrhages, or evidence of a prior cerebral macrohemorrhage
  • Presence at screening of any other significant cerebral abnormalities, including ARIA-E
  • Treatment with anticoagulation medications within 2 weeks prior to enrollment. Clopidogrel, dipyridamole, and aspirin are permitted
  • Treatment with anticholinergic antidepressants, typical antipsychotics, or barbiturates within 2 weeks prior to enrollment. All other antidepressants and atypical antipsychotics are allowed with certain restrictions as defined in the protocol
  • Chronic use of opiates, opioids, or benzodiazepines
  • Any biologic therapy within 75 weeks prior to enrollment
  • Any investigational agent (other than crenezumab) within 75 weeks prior to enrollment
  • Treatment with anticholinergic antidepressants, typical antipsychotics, barbiturates, or narcotics within 5 half-lives or 3 months prior to screening, whichever is longer. All other antidepressants and atypical antipsychotics are allowed. Chronic use of benzodiazepines is not allowed; however, the intermittent use of benzodiazepines is allowed, except within 2 days prior to any neurocognitive assessment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (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 Canada,   France,   Germany,   Spain,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01723826
Other Study ID Numbers  ICMJE GN28525
2012-003242-33 ( EudraCT Number )
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
Current Responsible Party Genentech, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Genentech, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Genentech, Inc.
PRS Account Genentech, Inc.
Verification Date February 2020

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