Phase II Trial to Evaluate Safety and Efficacy of GM-CSF/Sargramostim in Alzheimer's Disease

NCT04902703 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 19-27271R01AG071151-01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

A medicine that is FDA-approved for bone marrow stimulation (called sargramostim) will be tested for its safety and efficacy in individuals with mild-to-moderate Alzheimer's disease over a six month treatment period.

Conditions

Alzheimer Disease

Keywords

Alzheimer; Alzheimers Disease; sargramostim; GM-CSF; Leukine

Outcome Measures

Primary Outcomes (1)

• Safety as measured by number of Adverse Events (AEs) by body system

  The safety of sargramostim will be assessed through number of adverse events (AEs) by body system from consent to follow-up within a safety analysis set consisting of all individuals who were enrolled and and randomized and who received at least one injection of sargramostim or placebo.

  Informed consent to Follow-up Visit (38 weeks)

Secondary Outcomes (1)

• Mini-Mental State Examination

  Baseline to End of Treatment, Follow-up (30 weeks)

Other Outcomes (9)

• Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog13)

  Baseline to End of Treatment, Follow-up (30 weeks)

• Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)

  Baseline to End of Treatment, Follow-up (30 weeks)

• Trail Making Test - Part A (TMT-A)

  Baseline to End of Treatment, Follow-up (30 weeks)

Study Arms (2)

Sargramostim

EXPERIMENTAL

178.57 mcg/m2/day subcutaneously 7 days/week for 24 weeks

Drug: Sargramostim

Placebo Control - Saline

PLACEBO COMPARATOR

Placebo comparator (saline) subcutaneously 7days/week for 24 weeks

Drug: Saline - placebo comparator

Interventions

Saline - placebo comparator DRUG

Saline will be administered subcutaneously, 7 days/week, for 24 weeks

Also known as: Sterile solution of sodium chloride in water

Placebo Control - Saline

Sargramostim DRUG

Sargramostim is a granulocyte macrophage colony stimulating factor that will be administered at a dose of 178.57 mcg/m2 per day subcutaneously, 7 days/week, for 24 weeks

Also known as: Leukine, Granulocyte Macrophage Colony Stimulating Factor

Sargramostim

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females between age 60 and 85 years, inclusive, at time of consent.
• Have a dedicated partner/caregiver informant who is in the company of the participant at least 12 hours a week, who can accompany them to scheduled visits, and who is able to provide accurate reporting upon the behavioral, cognitive and functional abilities of the participant.
• Be physically able to participate with adequate visual acuity and auditory discrimination.
• Be willing / able to provide written informed consent or assent.
• Must reside within a proximity of the study site that will not preclude their regularly-scheduled participation in the trial, as well as a catchment area for local lab blood draws (i.e. central contracted laboratory).
• Meet criteria for probable AD dementia according to the National Institute of Aging - Alzheimer's Association (NIA-AA) 2018 core research criteria, and have the following at screening:
• A diagnosis of mild AD or moderate AD, or
• A provisional research diagnosis consistent with probable mild AD or moderate AD, and
• MoCA score of 4-24 inclusive.
• Have positive biomarker for brain amyloid pathology as shown by:
• Positive plasma assay for Aβ(42)/ Aβ(40) ratio AND
• Either postivie CSF assay for AD assessment or positive amyloid PET, per PI read.
• If receiving anti-dementia treatment (i.e. AChEI), be on stable treatment for at least 60 days (i.e., cholinesterase inhibitor and/or Memantine) before initial screening visit.
• Be stable on all other medications for at least 30 days prior to initial screening visit.
• Have had a dental exam within 6 months of date of screening.

You may not qualify if:

• Individuals with a first degree relative diagnosed with AD before 55 years of age.
• BMI ≥35.
• Is unable to read/write at an appropriate level to reliably participate in clinical trial psychometric assessments.
• Is a prisoner.
• Other neurological or psychiatric condition (other than AD) that can impact cognition, as well as atypical presentations of AD and AD related dementias, including logopenic primary progressive aphasia (PPA), or posterior cortical atrophy (PCA); or, CT/MRI evidence of potentially significant intracranial abnormalities not related to AD (e.g., evidence of major stroke or lacune in an area critical to cognition, infections, cancer, hydrocephalus, multiple sclerosis, etc.); or abnormal CSF not consistent with AD.
• Presence of current, serious mood or anxiety disorder, and/or a psychotic disorder, and/or a substance-related disorder according to Diagnostic and Statistical Manual of Psychiatric Disorders, Edition IV, text revision (DSM-IV-TR) or DSM-V that, in the opinion of the Principal Investigator, might impact cognitive assessment, affect participants ability to complete the study, or confound interpretation of the study drug effect; or is considered suicidal or shows suicidal ideation as assessed by the study physician
• History of deep vein thrombosis, pulmonary embolism, familial predisposition for deep vein thrombosis, or pulmonary embolism.
• History of a latex or yeast allergy.
• Presence/history of drug hypersensitivity; or known hypersensitivity to sargramostim, yeast-derived products, any other component of the product, or benzyl alcohol (present in bacteriostatic water or saline for injection).
• History of asplenia, hyposplenia, or splenectomy
• History of, or treatment for, an autoimmune disease (e.g. Rheumatoid Arthritis, Multiple Sclerosis, Myasthenia Gravis, etc.).
• Untreated or unstable medical condition that could interfere with the study assessments in the opinion of the study physician, or may require immune-stimulating, immune-suppressive, or immune-modulating treatment(s) during the conduct of the study.
• History of seizures (except infant febrile seizures).
• Pregnant or breastfeeding female, or female of childbearing potential and not protected by highly effective contraceptive method of birth control (i.e., oral or depot contraceptives or intrauterine device (IUD) or participant was surgically sterilized) and/or unwilling or unable to be tested for pregnancy; Male refusing to use condoms, if partner can get pregnant.
• MRI evidence of \>4 micro-hemorrhages; participants who may be prone to spontaneous ARIA-H and/or may be more susceptible to adverse effects of the ARIA-H.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator
• Alzheimer's Association: collaborator
• Partner Therapeutics, Inc.: collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Related Publications (1)

• Potter H, Woodcock JH, Boyd TD, Coughlan CM, O'Shaughnessy JR, Borges MT, Thaker AA, Raj BA, Adamszuk K, Scott D, Adame V, Anton P, Chial HJ, Gray H, Daniels J, Stocker ME, Sillau SH. Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer's disease. Alzheimers Dement (N Y). 2021 Mar 24;7(1):e12158. doi: 10.1002/trc2.12158. eCollection 2021.

  PMID: 33778150 RESULT

Related Links

• CU Alzheimer's and Cognition Center Clinical Research Portal

MeSH Terms

Conditions

Alzheimer Disease

Interventions

sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Water

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Huntington Potter, PhD

  University of Colorado Alzheimer's and Cognition Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Neurology Research, CU Department of Neurology

CONTACT

303-724-4644; NeuroResearch@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is double-blind, placebo-controlled in the Alzheimer's Disease population, and will include individuals with mild AD and moderate AD. Individuals who meet inclusion/exclusion criteria will be randomized in a double-blind manner, to receive either sargramostim 178. 57µg/m2/day subcutaneously (7 days per week) or placebo (7 days per week) in an approximate 2:1 randomization ratio.

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: May 26, 2021
• Study Start: June 1, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)