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CompletedNCT04381468SIGNAL-ADUpdated Aug 22, 2024

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

A Phase 1/2 interventional study of Pepinemab and Placebo in Alzheimer Disease, sponsored by Vaccinex Inc.. Completed at 14 sites in United States. Open to participants aged 55 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-08-22.

Sponsored by Vaccinex Inc. · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Primary completion was Jun 2024, 2 years 5 months ago, and no results have been posted to the registry.
Phase
Phase 1/2
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
55 Years to 85 Years
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Alzheimer Disease

Keywords

  • Mild Cognitive Impairment
  • Mild Alzheimer's Dementia
  • Early Alzheimer's Disease
  • VX15/2503
  • Semaphorin 4D
  • SEMA4D
  • monoclonal antibody
03

In context

Alzheimer Disease

3,965 studies on the registry are indexed under Alzheimer Disease; 926 are open to participants now.

This study's enrollment of 50 is below the median of 70 across 3,019 interventional studies indexed under Alzheimer Disease.

Browse Alzheimer Disease studies →

Lead sponsor

Vaccinex Inc. is the lead sponsor of 7 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
55 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Written from the participant and legally acceptable representative (trial partner).
  2. 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).
  3. Male and female participants between the ages of 55 to 85 (inclusive).

  4. If female, not be of 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.

  5. If male, must agree to use a reliable method of (condoms with contraceptive forms or sexual abstinence) during the study and for 6 months after the last dose of study drug.

  6. Must fulfill one of the following:

    1. 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
    2. A documented positive amyloid CSF result obtained at any time prior to the Screening visit; or
    3. Investigator has knowledge of positive amyloid PET scan or positive amyloid CSF result obtained previously; or
    4. 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
  7. Evidence of cognitive impairment based on history and neuropsychological testing that meet the diagnostic criteria for probable Alzheimer's dementia.
  8. Global Clinical Dementia Rating (CDR) of 0.5 or 1.0
  9. score of 17-26, inclusive.
  10. Adequate vision, hearing, and motor function to comply with testing.
  11. If receiving medications for AD (including but not limited to donepezil, rivastigmine, galantamine, tacrine, and memantine), be on a stable dose for at least 8 weeks prior to Screening Visit.
  12. If on stable doses of centrally-acting medications, be on a stable dose for 8 weeks prior to Screening Visit.
  13. In the opinion of the Investigator, is in reasonably good health over the last 6 months and any chronic disease is stable based on medical history and screening assessments.

Exclusion criteria

Exclusion

  1. Inability to comply with visit schedule or other protocol requirements.
  2. Have participated in an 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.
  3. Have a known allergy to any ingredient in the study drug formulation.
  4. Have a body weight greater than 125 kg.

  5. Are a suicide risk, as determined by meeting any of the following criteria:

    1. Suicide attempt within one year prior to the Baseline Visit.
    2. Suicidal ideation as defined by a positive response to question 4 and 5 on the C-SSRS within 60 days of the Baseline Visit.
  6. Have a history of substance abuse (based on DSMIV criteria) within the past 12 months prior to Screening.
  7. Significant acute or chronic infection at Screening including, among others: Known history of (HIV) or known acquired immunodeficiency syndrome. virus (HBV) or virus (HCV) infection (defined as, HBV surface antigen positive or positive HCV antibody with reflex to positive HCV RNA) at Screening.
  8. Have laboratory or abnormalities at Screening in the opinion of the Investigator.
  9. Have clinically relevant hematologic, hepatic, cardiac, or renal disease.
  10. 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 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.
  11. 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).

  12. Have any of the following conditions (which would exclude MRI or PET participation):

    1. 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.
    2. An implant/device/condition that is for MRI (e.g., pacemaker, severe claustrophobia, prosthetic heart valve, any metal fragments in the eyes or body--in some cases, an X-ray may be needed before an MRI scan, to ensure it is safe to enter the scanner).
    3. Body habitus that would impede completion of imaging scans.
  13. Has an MRI scan obtained at Screening that shows evidence of a neurological disorder other than early AD or > 4 cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as "possible" or "definite"), a single area of superficial siderosis,
  14. Any other clinically significant finding on MRI (e.g., any lesion that may account for their cognitive impairment, including but not limited to brain tumor, severe white matter disease arteriovenous malformation, cavernous hemangioma, or any infarct in a strategic cortical or subcortical location).
  15. Are undergoing FDG-PET and have received research-related radiation exposure that exceeds institutional guidelines in the prior year if applicable.
  16. Are undergoing a LP for CSF collection and have any of the following conditions: uncorrected bleeding or clotting disorders, skin infections near the site of the LP, suspicion of increased intracranial pressure, allergies to numbing medications (local anesthetics), acute spinal trauma.
  17. Are undergoing a LP for CSF collection and taking any of the following types of anticoagulants: coumarins and indandiones, Factor Xa inhibitors, heparins, or thrombin inhibitors.
  18. Has received treatment with any FDA accelerated approval therapy for treatment of Alzheimer's Disease
  19. Has a Screening MRI that shows Amyloid-related imaging abnormalities edema (ARIA-E)
Terms in these criteria, in plain language(12)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

MMSE and MoCA

Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
50 participants (actual)

Study arms

  • Experimental
    pepinemab 40mg/kg

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

    Drug: Pepinemab

  • Placebo comparator
    Placebo

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

    Drug: Placebo

Interventions

  • DrugPepinemab

    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

  • DrugPlacebo

    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

06

What researchers measure

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.

    Time frame: Up to 40 weeks

Secondary outcomes

  1. Effects on brain metabolism

    As assessed by \[18F\]fluorodeoxyglucose (FDG)-PET in the resting state following administration of 20 mg/kg or 40 mg/kg pepinemab or placebo.

    Time frame: Up to 36 weeks

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

    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.

    Time frame: Up to 36 weeks

  3. Clinical Dementia Rating (CDR)

    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.

    Time frame: Up to 36 weeks

  4. Mini Mental State Examination (MMSE)

    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.

    Time frame: Up to 36 weeks

  5. Alzheimer's Disease Cooperative Study - Activities of Daily Living

    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.

    Time frame: Up to 36 weeks

  6. Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (ADCS-CGIC)

    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.

    Time frame: Up to 36 weeks

  7. Neuropsychiatric Inventory (NPI)

    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.

    Time frame: Up to 36 weeks

  8. Immunogenicity of pepinemab in serum

    As assessed by the frequency and titer of anti-drug antibodies.

    Time frame: Up to 36 weeks

Other outcomes

  1. Peak serum concentration (Cmax)

    PK parameter

    Time frame: Up to 36 weeks

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

    PK parameter

    Time frame: Up to 36 weeks

  3. Half-life of pepinemab

    PK parameter

    Time frame: Up to 36 weeks

  4. Serum and CSF levels of neuroinflammatory cytokines

    IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL13,IFNγ, TNF-α, TGFβ

    Time frame: Up to 36 weeks

  5. T- and B-Cell Quantitation by Flow Cytometry (TBNK)

    B cells, total count; Natural killer (NK) cells, total count; T cells, total count; Absolute CD4/CD8 count with ratio

    Time frame: Up to 36 weeks

  6. Plasma and CSF concentration of neurofilament light chain (NfL)

    Time frame: Up to 36 weeks

  7. Plasma and CSF concentrations of Aβ1-42/Aβ1-40

    Time frame: Up to 36 weeks

  8. CSF levels of pepinemab

    Time frame: Up to 36 weeks

  9. CSF concentrations of tau and p-tau

    Time frame: Up to 36 weeks

  10. CSF concentrations of YKL-40

    Time frame: Up to 36 weeks

  11. Cellular SEMA4D levels

    PD parameter to determine the level of SEMA4D expression on T lymphocytes

    Time frame: Up to 36 weeks

  12. Total soluble SEMA4D levels

    PD parameter to determine levels of total soluble SEMA4D

    Time frame: Up to 36 weeks

  13. Effects on brain volume

    As measured by MRI

    Time frame: Up to 36 weeks

07

Study locations

14 sites
  • Pacific Research Network, Inc
    San Diego, California 92103, United States
  • Georgetown University
    Washington, District of Columbia 20057, United States
  • Brain Matters Research
    Delray Beach, Florida 33445, United States
  • Neuropsychiatric Research Center of Southwest Florida
    Fort Myers, Florida 33912, United States
  • JEM Research Institute
    Lake Worth, Florida 33462, United States
  • Premiere Research Institute of Palm Beach, Neurology
    Palm Beach, Florida 33480, United States
  • Brain Matters Research
    Stuart, Florida 34997, United States
  • Indiana University School of Medicine
    Indianapolis, Indiana 46202, United States
  • University of Kansas Medical Center
    Fairway, Kansas 66205, United States
  • Neurological Associates of Albany
    Albany, New York 12212, United States
  • Dent Neurological Associates
    Amherst, New York 14226, United States
  • Columbia University Irving Medical Center
    New York, New York 10032, United States
  • University of Rochester Medical Center
    Rochester, New York 14620, United States
  • Re-Cognition Health
    Fairfax, Virginia 22031, United States
08

References and documents

Publications

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09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jul 2021 to primary completion in Jun 2024, 34 months.

Of 62 phase 1/2 interventional studies under Alzheimer Disease, half reached primary completion within 45 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 63. This study's 34 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
May 1, 2020
First posted
May 8, 2020
StartActual
Jul 22, 2021
Primary completionActual
Jun 5, 2024
CompletionActual
Jun 5, 2024
Last update
Aug 22, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 22, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04381468
Lead sponsor
Vaccinex Inc.
Collaborators
Alzheimer's Drug Discovery Foundation, Alzheimer's Association
Responsible party
Sponsor
First posted
May 8, 2020
Start date
Jul 22, 2021
Primary completion
Jun 5, 2024
Completion
Jun 5, 2024
Last update
Aug 22, 2024

Study contacts

Eric Siemers, MD
study director · Vaccinex Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.

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Discussion

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Studies of the drug tested here: Pepinemab

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Vaccinex Inc.

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