Trial to Evaluate Safety and Efficacy of GM-CSF /Sargramostim in Down Syndrome

NCT05482334 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 22-13011R61AG074859-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This trial protocol is designed to evaluate primarily whether the use of sargramostim (recombinant human GM-CSF), administered five days per week for four consecutive weeks (20 treatment days), will be well tolerated by and safe for use in young adult participants with Down syndrome.

Conditions

Down Syndrome

Keywords

Down syndrome; Trisomy 21

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 (20 weeks)

Secondary Outcomes (1)

• Down syndrome Mental Status Exam (DSMSE)

  Baseline to End of Treatment, Follow-up (20 weeks)

Other Outcomes (8)

• Leiter 3 International Performance Scale (selected subtests)

  Baseline to End of Treatment, Follow-up (20 weeks)

• CANTAB - Cambridge Neuropsychological Test Automated Battery) (selected subtests)

  Baseline to End of Treatment, Follow-up (20 weeks)

• NEPSY II (selected subtest)

  Baseline to End of Treatment, Follow-up (20 weeks)

Study Arms (2)

Sargramostim

EXPERIMENTAL

Sargramostim 250 μg/m2/day subcutaneously (5 days per week)

Drug: Sargramostim for Injection

Placebo Control - Saline

PLACEBO COMPARATOR

Placebo equivalent volume subcutaneously (5 days per week)

Drug: Saline Placebo

Interventions

Sargramostim for Injection DRUG

Recombinant human GM-CSF

Also known as: Leukine, Granulocyte Macrophage Colony Stimulating Factor

Sargramostim

Saline Placebo DRUG

Bacteriostatic Saline

Also known as: Bacteriostatic Saline

Placebo Control - Saline

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females with Down syndrome between 18-35 years of age.
• A cytogenetic diagnosis of full trisomy 21 or complete unbalanced translocation of chromosome 21.
• 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 willing / able to provide written informed consent or assent. If assent is provided, consent must be provided by a legally authorized representative (LAR), who may or may not be the dedicated study partner / caregiver. Documentation of LAR status will follow local laws and regulations.
• Be physically able to participate by medical history, clinical exam, and other testing, with adequate visual acuity and auditory discrimination.
• Must reside within a proximity of the study site that will not preclude their regularly scheduled participation in the trial.
• Be willing to avoid pregnancy or fathering children for the duration of the study.
• Must have received recent testing for hypothyroidism during the past 6 months, and if positive for hypothyroidism, they must be stable on medications for treating hypothyroidism for at least 30 days prior to enrollment, and they must remain on their hypothyroidism treatments for the duration of the trial.
• Be stable on all other medications for at least 30 days prior to initial screening visit.

You may not qualify if:

• 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.
• Positive serology for hepatitis B surface antigen (HBs Ag), anti-hepatitis C virus (anti- HCV), anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2 Ab), or spirochetal infection (e.g., syphilis).
• Poor venous access not allowing repeated blood tests.
• 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).
• Concomitant treatment with other immunosuppressants (e.g., corticosteroids, methotrexate).
• History of deep vein thrombosis, pulmonary embolism, familial predisposition for deep vein thrombosis, or pulmonary embolism.
• History of asplenia, hyposplenia, or splenectomy (for any indication).
• Untreated or unstable medical condition that could interfere with the study assessments in the opinion of the study physician, or that may require immune-stimulating, immunesuppressive, or immune-modulating treatment(s) during the conduct of the study (e.g., therapeutic vaccines, cytokines, anti-cytokine monoclonal antibodies, etc.)
• History of seizures (except infant febrile seizures).
• Evidence of:
• pre-existing fluid retention (clinical or radiological);
• respiratory symptoms (e.g., dyspnea), moderate-to-severe lung disease (e.g., COPD, pulmonary infiltrates);
• cardiovascular symptoms or electrocardiographic evidence of cardiac disease that warrant therapeutic intervention (e.g., congestive heart failure, supraventricular arrhythmia, heart block, uncontrolled atrial fibrillation, etc.);
• a resting pulse less than 50, as assessed by the study physician;

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (2)

• 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

• Ahmed MM, Wang AC, Elos M, Chial HJ, Sillau S, Solano DA, Coughlan C, Aghili L, Anton P, Markham N, Adame V, Gardiner KJ, Boyd TD, Potter H. The innate immune system stimulating cytokine GM-CSF improves learning/memory and interneuron and astrocyte brain pathology in Dp16 Down syndrome mice and improves learning/memory in wild-type mice. Neurobiol Dis. 2022 Jun 15;168:105694. doi: 10.1016/j.nbd.2022.105694. Epub 2022 Mar 18.

  PMID: 35307513 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Down Syndrome

Interventions

sargramostim; Injections; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; 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

Study Officials

• Peter Pressman, MD

  CU Alzheimer's and Cognition Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: IP vs Placebo

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: August 1, 2022
• Study Start: October 23, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 2, 2025

Record last verified: 2025-03

Locations

US (1)