SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease (AD)
- Registration Number
- NCT04381468
- Lead Sponsor
- Vaccinex Inc.
- Brief Summary
To investigate safety, tolerability, the effects on cognition and brain metabolism of pepinemab in early AD dementia (early AD) subjects.
- Detailed Description
To investigate safety, tolerability, the effects on cognition and brain metabolism of pepinemab, administered as IV infusions every 4 weeks for 44 weeks (12 infusions) in mild dementia due to Alzheimer's Disease (AD)) participants. Participants will be randomized 1:1 to receive 40 mg/kg pepinemab or placebo.
This is a randomized double-blind, placebo-controlled study of pepinemab in mild dementia due to AD. The study is 52 weeks in duration, including a safety and efficacy evaluation 4 weeks after the last dose of study drug. Participants with resolved adverse events at Week 48 will have a safety telephone call at Week 52. Participants with unresolved adverse events at Week 48 will have a safety in-office visit at Week 52. The study protocol will include two sentinel participants in each of the two blinded dose arms. Sentinel dosing will be implemented by randomly assigning one study participant to one of the two dose arms in a blinded manner, treating those participants with study drug. If no unexpected serious adverse events are observed within 48 hours after the first and second participants receive treatment, two additional participants will be enrolled, with one participant assigned randomly to each of the two dose arms. Again a 48-hour safety period will be observed following treatment of the fourth participant to document any unexpected safety events that may occur. Should no unexpected serious adverse events occur within 48 hours after the third and fourth participants receive treatment, the remaining participants will be assigned to the study dose arms according to the blinded randomization scheme and the 1:1 randomization ratio. Participants will be randomized to one of two treatment arms and will receive one dose of study drug every 4 weeks during the 44-week dosing period for a total of 12 doses of study drug. The primary objective is the safety and tolerability of study drug. A key secondary objective is the change in brain metabolism as assessed by \[18F\]fluorodeoxyglucose (FDG)-PET in the resting state.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo .A placebo control will be administered via monthly intravenous infusions. pepinemab 40mg/kg Pepinemab The study drug, pepinemab, will be administered via monthly intravenous infusions.
- Primary Outcome Measures
Name Time Method Number of subjects with treatment emergent adverse events (TEAEs) Up to 40 weeks TEAEs are defined as Adverse events (AEs) with onset after date-time of first dose, or medical conditions present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP.
- Secondary Outcome Measures
Name Time Method Effects on brain metabolism Up to 36 weeks As assessed by \[18F\]fluorodeoxyglucose (FDG)-PET in the resting state following administration of 20 mg/kg or 40 mg/kg pepinemab or placebo.
Alzheimer's Disease Assessment Scale- Cognitive subscale (ADAS-cog13) Up to 36 weeks The Alzheimer's Disease Assessment Scale (ADAS-cog13) will be performed to test the cognition of subjects. The score ranges from 0 to 75，and higher values represent a better outcome.
Mini Mental State Examination (MMSE) Up to 36 weeks Mini-Mental State Examination scores(MMSE) will be performed to test the cognition of subjects. The score ranges from 0 to 30，and higher values represent a better outcome.
Alzheimer's Disease Cooperative Study - Activities of Daily Living Up to 36 weeks The ADCS-ADL assesses the competence of participants with AD in basic and instrumental activities of daily living (ADLs). It is administered by a clinician as a structured interview with a caregiver. The maximum score is 30. A higher score is better.
Clinical Dementia Rating (CDR) Up to 36 weeks The CDR assesses 3 domains of cognition (memory, orientation, judgment/problem solving) and 3 domains of function (community affairs, home/hobbies, personal care) using semi-structured interviews of both the study subject and an informant carried out by a trained rater. The CDR is scored using a standard methodology. Each domain is rated on a 5-point scale and lower numbers represent a better outcome.
Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (ADCS-CGIC) Up to 36 weeks The ADCS-CGIC focuses on clinicians' observations of change in the patient's cognitive, functional, and behavioral performance since the beginning of a trial. The ADCS-CGIC gives a discrete score that ranges from 1-7 with 7 being the worst outcome.
Neuropsychiatric Inventory (NPI) Up to 36 weeks The NPI is a trial partner interview-based rating scale assessing 12 behavioral disturbances occurring in dementia subjects. Items are scored for both frequency and severity. Total scores range from 0-144 with higher scores indicating greater behavioral disturbances. For each item, the associated trial partner distress is also assessed.
Immunogenicity of pepinemab in serum Up to 36 weeks As assessed by the frequency and titer of anti-drug antibodies.
Trial Locations
- Locations (13)
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
JEM Research Institute
🇺🇸Lake Worth, Florida, United States
Premiere Research Institute of Palm Beach, Neurology
🇺🇸Palm Beach, Florida, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
Brain Matters Research
🇺🇸Stuart, Florida, United States
Neuropsychiatric Research Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Pacific Research Network, Inc
🇺🇸San Diego, California, United States
Neurological Associates of Albany
🇺🇸Albany, New York, United States
Dent Neurological Associates
🇺🇸Amherst, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Re-Cognition Health
🇺🇸Fairfax, Virginia, United States
University of Kansas Medical Center
🇺🇸Fairway, Kansas, United States