SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease (AD) (SIGNAL-AD)
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|ClinicalTrials.gov Identifier: NCT04381468|
Recruitment Status : Recruiting
First Posted : May 8, 2020
Last Update Posted : October 22, 2021
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease||Drug: Pepinemab Drug: Placebo||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||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|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease (AD): A Multi-center, Randomized, Double-Blind, Placebo-Controlled Safety and Biomarker Study of Pepinemab Anti-SEMA4D Antibody in Early-AD|
|Actual Study Start Date :||July 22, 2021|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||January 31, 2023|
Experimental: pepinemab 40mg/kg
The study drug, pepinemab, will be administered via monthly intravenous infusions.
Pepinemab is a humanized IgG4 monoclonal antibody. The antibody is formulated at 20 mg/mL in 20 mM Sodium Acetate buffer, pH 5.4, containing 130 mM Sodium Chloride and 0.02% Polysorbate 80
Placebo Comparator: Placebo
.A placebo control will be administered via monthly intravenous infusions.
Placebo consists of formulation buffer only which is 20 mM Sodium Acetate buffer, pH 5.4, containing 130 mM Sodium Chloride and 0.02% Polysorbate 80
- Number of subjects with treatment emergent adverse events (TEAEs) [ Time Frame: 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.
- Effects on brain metabolism [ Time Frame: 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) [ Time Frame: 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.
- Clinical Dementia Rating (CDR) [ Time Frame: 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.
- Mini Mental State Examination (MMSE) [ Time Frame: 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 [ Time Frame: 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.
- Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (ADCS-CGIC) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Up to 36 weeks ]As assessed by the frequency and titer of anti-drug antibodies.
- Peak serum concentration (Cmax) [ Time Frame: Up to 36 weeks ]PK parameter
- Area under the serum concentration vs. time curve (AUC) [ Time Frame: Up to 36 weeks ]PK parameter
- Half-life of pepinemab [ Time Frame: Up to 36 weeks ]PK parameter
- Serum and CSF levels of neuroinflammatory cytokines [ Time Frame: Up to 36 weeks ]IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL13,IFNγ, TNF-α, TGFβ
- T- and B-Cell Quantitation by Flow Cytometry (TBNK) [ Time Frame: Up to 36 weeks ]B cells, total count; Natural killer (NK) cells, total count; T cells, total count; Absolute CD4/CD8 count with ratio
- Plasma and CSF concentration of neurofilament light chain (NfL) [ Time Frame: Up to 36 weeks ]
- Plasma and CSF concentrations of Aβ1-42/Aβ1-40 [ Time Frame: Up to 36 weeks ]
- CSF levels of pepinemab [ Time Frame: Up to 36 weeks ]
- CSF concentrations of tau and p-tau [ Time Frame: Up to 36 weeks ]
- CSF concentrations of YKL-40 [ Time Frame: Up to 36 weeks ]
- Cellular SEMA4D levels [ Time Frame: Up to 36 weeks ]PD parameter to determine the level of SEMA4D expression on T lymphocytes
- Total soluble SEMA4D levels [ Time Frame: Up to 36 weeks ]PD parameter to determine levels of total soluble SEMA4D
- Effects on brain volume [ Time Frame: Up to 36 weeks ]As measured by MRI
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04381468
|Contact: John Leonard, PhDemail@example.com|
|Contact: Megan Boisefirstname.lastname@example.org|
|United States, California|
|Pacific Research Network, Inc||Recruiting|
|San Diego, California, United States, 92103|
|Contact: Dixie Creager|
|United States, District of Columbia|
|Washington, District of Columbia, United States, 20057|
|Contact: Kelly McCann|
|United States, Florida|
|Brain Matters Research||Recruiting|
|Delray Beach, Florida, United States, 33445|
|Contact: Mark Brody, MD|
|Neuropsychiatric Research Center of Southwest Florida||Recruiting|
|Fort Myers, Florida, United States, 33912|
|Contact: Melissa Schaerf|
|Principal Investigator: Wendy Bond, MD|
|JEM Research Institute||Recruiting|
|Lake Worth, Florida, United States, 33462|
|Contact: Jayne Drew|
|Brain Matters Research||Recruiting|
|Stuart, Florida, United States, 34997|
|Contact: Mark Brody, MD|
|United States, Indiana|
|Indiana University School of Medicine||Recruiting|
|Indianapolis, Indiana, United States, 46202|
|Contact: Kala Hall|
|Principal Investigator: Martin Farlow, MD|
|United States, Kansas|
|University of Kansas Medical Center||Recruiting|
|Fairway, Kansas, United States, 66205|
|Contact: Rebecca Bothwell|
|Principal Investigator: Ryan Townley, MD|
|United States, Maryland|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Megan Schultz|
|Principal Investigator: Paul Rosenberg, MD|
|United States, Massachusetts|
|Boston Memory Clinic||Recruiting|
|Newton, Massachusetts, United States, 02459|
|Contact: Paula Levin|
|United States, New York|
|Columbia University Irving Medical Center||Not yet recruiting|
|New York, New York, United States, 10032|
|Contact: Katrina Cuasay|
|University of Rochester Medical Center||Recruiting|
|Rochester, New York, United States, 14620|
|Contact: Susan Salem-Spencer|
|Principal Investigator: Anton Porsteinsson, MD|
|Richmond Behavioral Associates||Recruiting|
|Staten Island, New York, United States, 10312|
|Contact: Adam Smith|
|United States, Virginia|
|Fairfax, Virginia, United States, 22031|
|Contact: Monica Bland|
|Principal Investigator: Scott Turner, MD|
|Study Director:||Eric Siemers, MD||Vaccinex Inc.|