Biomarker Assessments of Leukine During Treatment of Parkinson's Disease

NCT03790670 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 0839-18-FB
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

First, the investigators will determine the safety of a 36 month 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). This 36 month (n=10) pilot study will extend the prior 2 month observation tests towards the goal of assessing the safety of Leukine for treatment of Parkinson's disease (PD). 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). Second, we will assess regimen tolerability administered in a dose reduction, from 6 µg/kg/day without interruption, to 3 µg/kg/day with 2 day drug holidays. The investigators will examine over a time of 36 months, effects of treatment on defined adaptive immune deficits in PD as measured by analysis of peripheral blood mononuclear cells collected before, during, and after cessation of Leukine administration. Individual T cell parameters will be assessed and will include links between T cell function and subset analyses and clinical neurological signs and symptoms. In addition, the functional stability of the immune deficits will be assess in PD by examining T cell subsets in PD patients in this study against prior results. The investigators will also determine whether the 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 Disease

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Associated Adverse Events

  The safety of Leukine administration in PD will be examined by documenting abnormal results from CBC with differential, total T cell count, or comprehensive metabolic panel analyses; abnormal physical and or neurological exam findings; abnormal levels of antibodies to 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. These safety assessments will be made every four weeks.

  monthly during the course of treatment, up to 36 months, followed by 1 month drug cessation

Secondary Outcomes (3)

• Determination of Immune Cell Phenotype

  36 months of treatment, followed by 1 month drug cessation

• Determination of Immune Cell Number

  36 months of treatment, followed by 1 month drug cessation

• Determination of Immune Cell Function

  36 months of treatment, followed by 1 month drug cessation

Study Arms (1)

Leukine Treatment

EXPERIMENTAL

36 month 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; WBC\>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 amphet-amines or systemic corticosteroids) within 90 days

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (6)

• 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

• Saunders JA, Estes KA, Kosloski LM, Allen HE, Dempsey KM, Torres-Russotto DR, Meza JL, Santamaria PM, Bertoni JM, Murman DL, Ali HH, Standaert DG, Mosley RL, Gendelman HE. CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson's disease. J Neuroimmune Pharmacol. 2012 Dec;7(4):927-38. doi: 10.1007/s11481-012-9402-z. Epub 2012 Oct 11.

  PMID: 23054369 BACKGROUND

• Kosloski LM, Kosmacek EA, Olson KE, Mosley RL, Gendelman HE. GM-CSF induces neuroprotective and anti-inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxicated mice. J Neuroimmunol. 2013 Dec 15;265(1-2):1-10. doi: 10.1016/j.jneuroim.2013.10.009. Epub 2013 Oct 29.

  PMID: 24210793 BACKGROUND

• Sil S, Du X, Akter S, Kumar M, Oludipe DB, Saha A, Hu G, Ostlund KR, Haynatzki GR, Santamaria P, Mosley RL, Gendelman HE. A Hypothesis-Generating Pharmacologic Profile for Sargramostim Treatment of Parkinson's Disease. Cell Mol Neurobiol. 2026 Apr 1. doi: 10.1007/s10571-026-01717-7. Online ahead of print. No abstract available.

  PMID: 41920366 DERIVED

• Olson KE, Abdelmoaty MM, Namminga KL, Lu Y, Obaro H, Santamaria P, Mosley RL, Gendelman HE. An open-label multiyear study of sargramostim-treated Parkinson's disease patients examining drug safety, tolerability, and immune biomarkers from limited case numbers. Transl Neurodegener. 2023 May 22;12(1):26. doi: 10.1186/s40035-023-00361-1.

  PMID: 37217980 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

sargramostim

Condition Hierarchy (Ancestors)

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

Study Officials

• Howard 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 18, 2018
• First Posted: January 2, 2019
• Study Start: January 30, 2019
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: December 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)