Biomarker Validation Following Sargramostim Treatment in Parkinson's Disease

NCT05677633 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 0748-22-FB
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators will evaluate the safety of a 48 week regimen of Leukine administered as a weight-based dose at 3 ug/kg/ day for 5 days followed by a 2-day holiday. This 48 week long study will extend the prior biomarker evaluations observed in a previous study. Clinical signs and symptoms will be measured by personal well-being, physical, and neurological examinations (UPDRS Parts I, II, III, and IV assessments) and blood tests (CBC with differential, total T cell count, and a comprehensive metabolic sera panel). Leukapheresis will be performed to collect large numbers of immune cells for biomarker testing and immune phenotyping. Additionally, the investigators will determine whether immune deficits of PD are consistent during baseline data collection, and the potential Leukine-induced motor control and mobility improvements will be determined by UPDRS part I, II, III, and IV scores off treatment and on treatment.

Conditions

Parkinson's Disease and Parkinsonism

Keywords

Leukine; sargramostim; biomarker

Outcome Measures

Primary Outcomes (1)

• Change in incidence of adverse events over time

  The safety of Leukine administration in PD will be examined by documenting abnormal results from complete blood count (CBC) with differential, total T cell count, or comprehensive metabolic panel analyses; abnormal physical and or neurological exam findings; abnormal levels of antibodies to Granulocyte-macrophage colony-stimulating factor (GM-CSF); clinically increasing Unified Parkinson's disease Rating Scale (UPDRS) part I, II, III, and IV scores as determined by the examining physician; and other adverse events. Adverse event logs will be reported every 4 weeks.

  every 6 months during the course of treatment, up to 48 weeks until drug cessation

Secondary Outcomes (1)

• Change in Treatment Biomarkers over time

  every 6 months during the course of treatment, up to 48 weeks until drug cessation

Study Arms (1)

Leukine Treatment

EXPERIMENTAL

48 week regimen of Leukine administered as a weight-based dose at 3 µg/kg/day for 5 days (week), followed by a 2-day holiday (weekend)

Drug: Sargramostim

Interventions

Sargramostim DRUG

Recombinant human GM-CSF produced by recombinant DNA technology using a yeast (S. cerevisiae) expression system

Also known as: Leukine

Leukine Treatment

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Onset of bradykinesia and 1 or both of the following: rest tremor and/or rigidity
• Asymmetric onset of clinical signs
• Progressive motor symptoms
• Age at onset 35-85 years
• Duration of PD symptoms of at least 3 years
• Female subjects must be either:
• Not pregnant, not breastfeeding, and not planning on becoming pregnant during the study;
• Not of childbearing potential, defined as one who has been postmenopausal for at least 1 year and with follicle stimulating hormone (FSH) levels in the laboratory defined postmenopausal range, or has been surgically sterilized, or has had a hysterectomy at least 3 months prior to the start of this trial; or
• If of childbearing potential, must agree to use an effective method of avoiding pregnancy to the end of the trial and must have a negative serum beta-human chorionic gonadotropin (β-HCG) test. Effective methods of avoiding pregnancy are contraceptive methods used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, diaphragm with spermicide, male or female condoms with spermicide, or cervical cap), abstinence, or a sterile sexual partner.
• Must be stage 4 or less according to the Hoehn and Yahr scale

You may not qualify if:

• Atypical features indicative of a Parkinson-Plus disorder (Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), Corticobasal Degeneration (CBD)) including cerebellar signs, supranuclear gaze palsy, apraxia and other cortical signs, or prominent autonomic failure
• Neuroleptic treatment at time of onset of parkinsonism
• Active treatment with a neuroleptic at time of study entry
• History of repeated strokes with stepwise progression of parkinsonism
• History of repeated head injury
• History of definite encephalitis
• More than one blood relative diagnosed with PD
• Prominent gait imbalance early in the course (\< 5 years)
• Mini-mental state examination score \<26
• Hematological malignancy or coagulopathy
• Abnormal blood analyses: hematocrit \<30; white blood cell count \>11.5; clinically significant laboratory data (e.g. alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3x the upper limit of normal (ULN), or any abnormal laboratory value that could interfere with the assessment of safety in the judgment of the investigator; significant abnormalities on the clinical examination, vital signs, and clinical chemistry or hematology results (excluding findings of Parkinson's disease), that may interfere with the study or present a safety risk for the subject as judged by the clinical investigator charged in the care of study participants
• Serious medical illness or co-morbidity that may interfere with participation in the study
• Brain surgery for parkinsonism (DBS, cell implantation, gene therapy)
• History of an autoimmune disorder or systemic inflammatory disorder deemed significant by physician
• Immunostimulatory or immunosuppressive treatment (including amphetamines or systemic corticosteroids) within 90 days

Sponsors & Collaborators

• University of Nebraska: lead
• Partner Therapeutics, Inc.: collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (3)

• Olson KE, Namminga KL, Lu Y, Schwab AD, Thurston MJ, Abdelmoaty MM, Kumar V, Wojtkiewicz M, Obaro H, Santamaria P, Mosley RL, Gendelman HE. Safety, tolerability, and immune-biomarker profiling for year-long sargramostim treatment of Parkinson's disease. EBioMedicine. 2021 May;67:103380. doi: 10.1016/j.ebiom.2021.103380. Epub 2021 May 14.

  PMID: 34000620 BACKGROUND

• Abdelmoaty MM, Machhi J, Yeapuri P, Shahjin F, Kumar V, Olson KE, Mosley RL, Gendelman HE. Monocyte biomarkers define sargramostim treatment outcomes for Parkinson's disease. Clin Transl Med. 2022 Jul;12(7):e958. doi: 10.1002/ctm2.958.

  PMID: 35802825 BACKGROUND

• Gendelman HE, Zhang Y, Santamaria P, Olson KE, Schutt CR, Bhatti D, Shetty BLD, Lu Y, Estes KA, Standaert DG, Heinrichs-Graham E, Larson L, Meza JL, Follett M, Forsberg E, Siuzdak G, Wilson TW, Peterson C, Mosley RL. Evaluation of the safety and immunomodulatory effects of sargramostim in a randomized, double-blind phase 1 clinical Parkinson's disease trial. NPJ Parkinsons Dis. 2017 Mar 23;3:10. doi: 10.1038/s41531-017-0013-5. eCollection 2017.

  PMID: 28649610 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders

Interventions

sargramostim

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Howard E Gendelman, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: January 10, 2023
• Study Start: January 19, 2023
• Primary Completion: April 12, 2024
• Study Completion: November 1, 2024
• Last Updated: November 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)