SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease (AD)

NCT04381468 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: VX15/2503-11
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 14

Brief Summary

To investigate safety, tolerability, the effects on cognition and brain metabolism of pepinemab in early AD dementia (early AD) subjects.

Conditions

Alzheimer Disease

Keywords

Mild Cognitive Impairment; Mild Alzheimer's Dementia; Early Alzheimer's Disease; VX15/2503; Semaphorin 4D; SEMA4D; monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• Number of subjects with treatment emergent adverse events (TEAEs)

  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.

  Up to 40 weeks

Secondary Outcomes (8)

• Effects on brain metabolism

  Up to 36 weeks

• Alzheimer's Disease Assessment Scale- Cognitive subscale (ADAS-cog13)

  Up to 36 weeks

• Clinical Dementia Rating (CDR)

  Up to 36 weeks

• Mini Mental State Examination (MMSE)

  Up to 36 weeks

• Alzheimer's Disease Cooperative Study - Activities of Daily Living

  Up to 36 weeks

Other Outcomes (13)

• Peak serum concentration (Cmax)

  Up to 36 weeks

• Area under the serum concentration vs. time curve (AUC)

  Up to 36 weeks

• Half-life of pepinemab

  Up to 36 weeks

Study Arms (2)

pepinemab 40mg/kg

EXPERIMENTAL

The study drug, pepinemab, will be administered via monthly intravenous infusions.

Drug: Pepinemab

Placebo

PLACEBO COMPARATOR

.A placebo control will be administered via monthly intravenous infusions.

Drug: Placebo

Interventions

Pepinemab DRUG

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

pepinemab 40mg/kg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent from the participant and legally acceptable representative (trial partner).
• Have a reliable and competent trial partner who must have a close relationship with the participant, who has face to face contact at least three days a week for a minimum of ten waking hours a week and is willing to accompany the participant to all trial visits. The trial partner should understand the nature of the trial and adhere to trial requirements (e.g., dose, visit schedules, receive phone calls, and evaluations).
• Male and female participants between the ages of 55 to 85 (inclusive).
• If female, not be of childbearing potential as indicated by one of the following:
• a. Has reached natural menopause defined as either: i. ≥ 12 months of spontaneous amenorrhea or ii. ≥ 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels \> 40 mIU/ml as determined by the central laboratory; b. Has had a hysterectomy; or c. Has had a bilateral tubal ligation; or d. Has had a bilateral oophorectomy (with or without a hysterectomy) and more than 6 weeks have passed since the surgery.
• If male, must agree to use a reliable method of birth control (condoms with contraceptive forms or sexual abstinence) during the study and for 6 months after the last dose of study drug.
• Must fulfill one of the following:
• A documented amyloid PET scan (florbetaben F18, florbetapir F18, or flutametamol F18) determined as positive by the Investigator obtained at any time prior to the Screening visit; or
• A documented positive amyloid CSF result obtained at any time prior to the Screening visit; or
• Investigator has knowledge of positive amyloid PET scan or positive amyloid CSF result obtained previously; or
• A positive amyloid CSF result at screening. The cut-off value for CSF Aβ1-42 or CSF Aβ1-42/Aβ1-40 ratio will be based on the value determined by Vaccinex
• Evidence of cognitive impairment based on history and neuropsychological testing that meet the diagnostic criteria for probable Alzheimer's dementia.
• Global Clinical Dementia Rating (CDR) of 0.5 or 1.0
• MMSE score of 17-26, inclusive.
• Adequate vision, hearing, and motor function to comply with testing.

You may not qualify if:

• Inability to comply with visit schedule or other protocol requirements.
• Have participated in an investigational drug or device study within 30 days of the Baseline Visit. If previous investigational drug was a monoclonal antibody, antibody-drug conjugate, or similar protein therapeutic, 180 days or 5 half-lives, whichever occurs first.
• Have a known allergy to any ingredient in the study drug formulation.
• Have a body weight greater than 125 kg.
• Are a suicide risk, as determined by meeting any of the following criteria:
• Suicide attempt within one year prior to the Baseline Visit.
• Suicidal ideation as defined by a positive response to question 4 and 5 on the C-SSRS within 60 days of the Baseline Visit.
• Have a history of substance abuse (based on DSMIV criteria) within the past 12 months prior to Screening.
• Significant acute or chronic infection at Screening including, among others: Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as, HBV surface antigen positive or positive HCV antibody with reflex to positive HCV RNA) at Screening.
• Have clinically significant laboratory or ECG abnormalities at Screening in the opinion of the Investigator.
• Have clinically relevant hematologic, hepatic, cardiac, or renal disease.
• Have a clinically significant medical, surgical, laboratory, or behavioral abnormality which in the judgment of the Investigator makes the participant unsuitable for the study, as well as anyone with a history of malignancy of any type within 2 years of Screening. Persons with a history of surgically excised non-melanoma skin cancers, superficial bladder or prostate cancer are permitted.
• Participants who have a diagnosis of a neurological condition causing cognitive impairment other than sporadic mild dementia due to AD (e.g., Lewy body disease or frontotemporal dementia), a primary psychiatric diagnosis (e.g., Cognitive Impairment due to Schizophrenia, CIAS), history of frequent concussions or significant findings on brain MRI at screening inconsistent with AD (e.g., cerebrovascular disease or tumor).
• Have any of the following conditions (which would exclude MRI or PET participation):
• Participants deemed unable to cooperate due to claustrophobia, inability to lie on scanner bed for 45 minutes, or inability to achieve venous access sufficient for tracer or pepinemab administration.

Sponsors & Collaborators

• Vaccinex Inc.: lead
• Alzheimer's Drug Discovery Foundation: collaborator
• Alzheimer's Association: collaborator

Study Sites (14)

Pacific Research Network, Inc

San Diego, California, 92103, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Neuropsychiatric Research Center of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

JEM Research Institute

Lake Worth, Florida, 33462, United States

Location

Premiere Research Institute of Palm Beach, Neurology

Palm Beach, Florida, 33480, United States

Location

Brain Matters Research

Stuart, Florida, 34997, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

Location

Neurological Associates of Albany

Albany, New York, 12212, United States

Location

Dent Neurological Associates

Amherst, New York, 14226, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14620, United States

Location

Re-Cognition Health

Fairfax, Virginia, 22031, United States

Location

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MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

pepinemab

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Eric Siemers, MD

  Vaccinex Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: May 1, 2020
• First Posted: May 8, 2020
• Study Start: July 22, 2021
• Primary Completion: June 5, 2024
• Study Completion: June 5, 2024
• Last Updated: August 22, 2024

Record last verified: 2024-08

Locations

US (14)