VY7523-102: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study in Participants With Early Alzheimer's Disease

NCT06874621 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: VY7523-102
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 23

Brief Summary

This study is to be conducted in participants with early Alzheimer's Disease to test VY7523, a new drug being researched for treatment of Alzheimer's Disease. This study will look at how safe the drug is and how it works in the brain. It was first tested in normal, healthy participants who volunteered to participate. The study will look at three different dose levels, starting with the lowest dose first and moving to higher doses and more participants after safety has been reviewed by doctors and researchers. Some patients will receive drug while others will receive placebo. This will help to better compare how the drug works between participants receiving drug and placebo. The study will last up to 6 months for the lower dose groups and 12 months for the highest dose group.

Conditions

Alzheimer's Disease (AD)

Outcome Measures

Primary Outcomes (1)

• Characterization of the safety and tolerability of VY7523 in participants with early AD

  Incidence of treatment-emergent adverse events (TEAEs) and clinically significant changes from baseline

  Cohorts 1 and 2: up to 6 months Cohort 3: up to 12 months

Secondary Outcomes (4)

• To characterize the pharmacokinetics (PK) of VY7523 in serum

  Cohort 1 & 2: Month 1 - 6 Cohort 3: Month 1-7, 9, 12

• To evaluate the ability of VY7523 to prevent the spread of pathologic tau; Cohort 3 only

  Month 6, 12

• To evaluate the immunogenicity of multiple, escalating intravenous (IV) doses of VY7523

  Cohort 1 & 2: Month 1, 3, 4, 5 & 6 Cohort 3: Month 1, 2, 6, 9, 12

• To characterize the pharmacokinetics (PK) of VY7523 in cerebrospinal fluid (CSF) concentrations following multiple IV doses

  Cohort 1 & 2: Month 6 Cohort 3: Month 12

Study Arms (6)

Cohort 1 active

EXPERIMENTAL

Low dose VY7523

Drug: VY7523

Cohort 1 placebo

PLACEBO COMPARATOR

VY7523 matching placebo for Cohort 1 active dose

Drug: Placebo Comparator

Cohort 2 active

EXPERIMENTAL

mid dose VY7523

Drug: VY7523

Cohort 2 placebo

PLACEBO COMPARATOR

VY7523 matching placebo for Cohort 2 active dose

Drug: Placebo Comparator

Cohort 3 active

EXPERIMENTAL

high dose VY7523

Drug: VY7523

Cohort 3 placebo

PLACEBO COMPARATOR

VY7523 matching placebo for Cohort 3 active dose

Drug: Placebo Comparator

Interventions

VY7523 DRUG

VY7523 is a recombinant humanized immunoglobulin gamma 4 (IgG4) monoclonal antibody targeting human pathological tau

Cohort 1 active; Cohort 2 active; Cohort 3 active

Placebo Comparator DRUG

Matching placebo to VY7523

Cohort 1 placebo; Cohort 2 placebo; Cohort 3 placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of early AD, defined as:
• Meet the NIA-AA core clinical criteria for MCI due to AD or mild AD.
• Mini Mental State Examination (MMSE) score between 18 and 30, inclusive, at Screening (Cohort 1 and 2) and score between 22 and 30, inclusive, at Screening (Cohort 3).
• Report a history of subjective memory decline with gradual onset and slow progression over at least the last 6 months before Screening; must be corroborated by an informant/caregiver.
• CDR Memory Box score ≥0.5 CDR global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD.
• Evidence of pathology consistent with AD diagnosis:
• For Cohort 1 and Cohort 2 only, by documented historical amyloid PET showing imaging agent uptake into the brain conducted within 24 months before screening OR elevated plasma pTau217/np-Tau217 ratio within the Screening Period.
• For Cohort 3 only, evidence of pathology consistent with AD diagnosis by both:
• Evidence of Tau PET imaging agent uptake into the brain by central read AND
• Evidence of positive brain amyloid pathology as indicated by one of the following:
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• Documented historical amyloid PET showing imaging agent uptake into the brain conducted within 24 months before screening OR
• CSF beta amyloid and tau levels consistent with AD diagnosis within the Screening Period.
• Body mass index (BMI) ≥18 and ≤35 kg/m2 at Screening.
• Apart from the clinical diagnosis of early AD, participant must be in good health, based on medical history and screening assessments.

You may not qualify if:

• Any medical or neurological/neurodegenerative or psychiatric condition (other than AD) that, in the opinion of the Investigator, may be contributing cause to cognitive impairment or could confound interpretation of drug effect, affect study assessments, or affect participant's ability to participate and complete the study or lead to safety concerns.
• History of transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening.
• History of seizures within 10 years prior to screening or history of epileptic syndrome (except for history of febrile seizures in childhood)
• Lifetime history of a major psychiatric disorder including schizophrenia or bipolar disorder. History of major depressive disorder that has resulted in 2 or more hospitalizations in a lifetime.
• Presence of a clinically significant uncontrolled medical disorder involving one or more of these major organ systems: cardiovascular (including but not limited to a QTcF of \>470 ms for women and \>450 ms for men and uncontrolled hypertension), respiratory, renal, gastrointestinal, immunologic, hematologic including bleeding disorder, hepatic, or endocrine.
• Contraindications to lumbar puncture, including but not limited to coagulation or bleeding disorders, unsafe suspension of anticoagulant, infections at the injection site, spinal deformities or previous spinal surgeries that may affect safe LP performance, or conditions associated with increased intracranial pressure.
• Contraindications to MRI scanning, including but not limited to cardiac pacemaker/defibrillator, ferromagnetic metal implants (devices other than those approved as safe for use in MRI scanners).
• History of a malignant disease (cancer) except for resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, in situ prostate cancer with a normal posttreatment prostate-specific antigen within the last five years or other cancers in remission for at least 5 years
• Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic mAbs (or derivatives of mAbs), systemic immunosuppressants, or plasmapheresis during the study.
• History of severe allergies, or history of an anaphylactic reaction (nonactive hay fever is acceptable).
• Participation in a clinical drug trial or device within 30 days (or 5 half-lives, whichever is longer and 3 months for a biologic) of screening, unless the study blind has been broken and the participant was known to be on placebo.
• Last administration of B-secretase and gamma-secretase inhibitors in a study within 3 months or 5 half-lives (whichever is longer) prior to screening, unless it can be documented that the participant only received placebo.
• Current use of an approved AD disease modifying or anti-amyloid therapy (including but not limited to any mAb therapies).
• Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant at an increased risk for intraoperative or postoperative bleeding.

Sponsors & Collaborators

• Voyager Therapeutics: lead

Study Sites (23)

VYGR Site 840018

Los Angeles, California, 90033, United States

Location

VYGR Site 840016

Orange, California, 92866, United States

Location

VYGR Site 840022

San Francisco, California, 94158, United States

Location

VYGR Site 840008

Stamford, Connecticut, 06905, United States

Location

VYGR Site 840005

Delray Beach, Florida, 33445, United States

Location

VYGR Site 840021

Fort Myers, Florida, 33912, United States

Location

VYGR Site 840010

Lady Lake, Florida, 32159, United States

Location

VYGR Site 840015

Miami, Florida, 33126, United States

Location

VYGR Site 840014

Miami, Florida, 33135, United States

Location

VYGR Site 840024

Miami, Florida, 33137, United States

Location

VYGR Site 840006

Orlando, Florida, 32803, United States

Location

VYGR Site 840003

Stuart, Florida, 34997, United States

Location

VYGR Site 840004

The Villages, Florida, 32162, United States

Location

VYGR Site 840002

Wellington, Florida, 33414, United States

Location

VYGR Site 840020

Winter Park, Florida, 32789, United States

Location

VYGR Site 840007

Decatur, Georgia, 30030, United States

Location

VYGR Site 840012

Toms River, New Jersey, 08755, United States

Location

VYGR Site 840009

Matthews, North Carolina, 28105, United States

Location

VYGR Site 840011

Plymouth Meeting, Pennsylvania, 19462, United States

Location

VYGR Site 124002

Ottawa, Ontario, K1Z1G3, Canada

Location

VYGR Site 124001

Toronto, Ontario, M3B2S7, Canada

Location

VYGR Site 124003

Montreal, Quebec, H3G1H9, Canada

Location

VYGR Site 124004

Montreal, Quebec, H4A3T2, Canada

Location

Study Officials

• Chief Medical Officer

  Voyager Therapuetics, 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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2025
• First Posted: March 13, 2025
• Study Start: March 3, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

US (19); CA (4)