SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease (AD)
- Conditions
- Alzheimer Disease
- Registration Number
- NCT04381468
- Lead Sponsor
- Vaccinex Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- Not specified
Inclusion<br><br> 1. Written informed consent from the participant and legally acceptable representative<br> (trial partner).<br><br> 2. Have a reliable and competent trial partner who must have a close relationship with<br> the participant, who has face to face contact at least three days a week for a<br> minimum of ten waking hours a week and is willing to accompany the participant to<br> all trial visits. The trial partner should understand the nature of the trial and<br> adhere to trial requirements (e.g., dose, visit schedules, receive phone calls, and<br> evaluations).<br><br> 3. Male and female participants between the ages of 55 to 85 (inclusive).<br><br> 4. If female, not be of childbearing potential as indicated by one of the following:<br><br> a. Has reached natural menopause defined as either: i. = 12 months of spontaneous<br> amenorrhea or ii. = 6 months of spontaneous amenorrhea with serum follicle<br> stimulating hormone (FSH) levels > 40 mIU/ml as determined by the central<br> laboratory; b. Has had a hysterectomy; or c. Has had a bilateral tubal ligation; or<br> d. Has had a bilateral oophorectomy (with or without a hysterectomy) and more than 6<br> weeks have passed since the surgery.<br><br> 5. If male, must agree to use a reliable method of birth control (condoms with<br> contraceptive forms or sexual abstinence) during the study and for 6 months after<br> the last dose of study drug.<br><br> 6. Must fulfill one of the following:<br><br> 1. A documented amyloid PET scan (florbetaben F18, florbetapir F18, or<br> flutametamol F18) determined as positive by the Investigator obtained at any<br> time prior to the Screening visit; or<br><br> 2. A documented positive amyloid CSF result obtained at any time prior to the<br> Screening visit; or<br><br> 3. Investigator has knowledge of positive amyloid PET scan or positive amyloid CSF<br> result obtained previously; or<br><br> 4. A positive amyloid CSF result at screening. The cut-off value for CSF Aß1-42 or<br> CSF Aß1-42/Aß1-40 ratio will be based on the value determined by Vaccinex<br><br> 7. Evidence of cognitive impairment based on history and neuropsychological testing<br> that meet the diagnostic criteria for probable Alzheimer's dementia.<br><br> 8. Global Clinical Dementia Rating (CDR) of 0.5 or 1.0<br><br> 9. MMSE score of 17-26, inclusive.<br><br> 10. Adequate vision, hearing, and motor function to comply with testing.<br><br> 11. If receiving medications for AD (including but not limited to donepezil,<br> rivastigmine, galantamine, tacrine, and memantine), be on a stable dose for at least<br> 8 weeks prior to Screening Visit.<br><br> 12. If on stable doses of centrally-acting medications, be on a stable dose for 8 weeks<br> prior to Screening Visit.<br><br> 13. In the opinion of the Investigator, is in reasonably good health over the last 6<br> months and any chronic disease is stable based on medical history and screening<br> assessments.<br><br>Exclusion<br><br> 1. Inability to comply with visit schedule or other protocol requirements.<br><br> 2. Have participated in an investigational drug or device study within 30 days of the<br> Baseline Visit. If previous investigational drug was a monoclonal antibody,<br> antibody-drug conjugate, or similar protein therapeutic, 180 days or 5 half-lives,<br> whichever occurs first.<br><br> 3. Have a known allergy to any ingredient in the study drug formulation.<br><br> 4. Have a body weight greater than 125 kg.<br><br> 5. Are a suicide risk, as determined by meeting any of the following criteria:<br><br> 1. Suicide attempt within one year prior to the Baseline Visit.<br><br> 2. Suicidal ideation as defined by a positive response to question 4 and 5 on the<br> C-SSRS within 60 days of the Baseline Visit.<br><br> 6. Have a history of substance abuse (based on DSMIV criteria) within the past 12<br> months prior to Screening.<br><br> 7. Significant acute or chronic infection at Screening including, among others: Known<br> history of human immunodeficiency virus (HIV) or known acquired immunodeficiency<br> syndrome. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as,<br> HBV surface antigen positive or positive HCV antibody with reflex to positive HCV<br> RNA) at Screening.<br><br> 8. Have clinically significant laboratory or ECG abnormalities at Screening in the<br> opinion of the Investigator.<br><br> 9. Have clinically relevant hematologic, hepatic, cardiac, or renal disease.<br><br> 10. Have a clinically significant medical, surgical, laboratory, or behavioral<br> abnormality which in the judgment of the Investigator makes the participant<br> unsuitable for the study, as well as anyone with a history of malignancy of any type<br> within 2 years of Screening. Persons with a history of surgically excised<br> non-melanoma skin cancers, superficial bladder or prostate cancer are permitted.<br><br> 11. Participants who have a diagnosis of a neurological condition causing cognitive<br> impairment other than sporadic mild dementia due to AD (e.g., Lewy body disease or<br> frontotemporal dementia), a primary psychiatric diagnosis (e.g., Cognitive<br> Impairment due to Schizophrenia, CIAS), history of frequent concussions or<br> significant findings on brain MRI at screening inconsistent with AD (e.g.,<br> cerebrovascular disease or tumor).<br><br> 12. Have any of the following conditions (which would exclude MRI or PET participation):<br><br> 1. Participants deemed unable to cooperate due to claustrophobia, inability to lie<br> on scanner bed for 45 minutes, or inability to achieve venous access sufficient<br> for tracer or pepinemab administration.<br><br> 2. An implant/device/condition that is contraindicated for MRI (e.g., pacemaker,<br> severe claustrophobia, prosthetic heart valve, any metal fragments in the eyes<br> or body--in some cases, an X-ray may be needed before an MRI scan, to ensure it<br> is safe to enter the scanner).<br><br> 3. Body habitus that would impede completion of imaging scans.<br><br> 13. Has an MRI scan obtained at Screening that shows evidence of a neurological disorder<br> other than early AD or > 4 cerebral microhemorrhages (regardless of their anatomical<br> location or diagnostic characterization as possible or definite), a single area<br> of superficial siderosis,<br><br> 14. Any other clinically significant finding on MRI (e.g., any lesion that may account<br> for their cognitive impairment, including but not limited to brain tumor, severe<br> white matter disease arteriovenous malformation, cavernous hemangioma, or any<br> infarct in a strategic cortical or subcortical location).<br><br> 15. Are undergoing FDG-PET and have received research-related radiation exposure that<br> exceeds institutional guidelines in the prior year if applicable.<br><br> 16. Are undergoing a LP for CSF collection and have any of the following conditions:<br> uncorrected bleeding or clotting disorders, skin infections near the site of the LP,<br> suspicion of increased intracranial pressure, allergies to numbing medications<br> (local anesthetics), acute spinal trauma.<br><br> 17. Are undergoing a LP for CSF collection and taking any of the following types of<br> anticoagulants: coumarins and indandiones, Factor Xa inhibitors, heparins, or<br> thrombin inhibitors.<br><br> 18. Has received treatment with any FDA accelerated approval therapy for treatment of<br> Alzheimer's Disease<br><br> 19. Has
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Number of subjects with treatment emergent adverse events (TEAEs)
- Secondary Outcome Measures
Name Time Method Effects on brain metabolism;Alzheimer's Disease Assessment Scale- Cognitive subscale (ADAS-cog13);Clinical Dementia Rating (CDR);Mini Mental State Examination (MMSE);Alzheimer's Disease Cooperative Study - Activities of Daily Living;Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (ADCS-CGIC);Neuropsychiatric Inventory (NPI);Immunogenicity of pepinemab in serum