Phase II Trial to Evaluate Safety and Efficacy of GM-CSF /Sargramostim in Down Syndrome
Overview
- Phase
- Phase 2
- Intervention
- Sargramostim for Injection
- Conditions
- Down Syndrome
- Sponsor
- University of Colorado, Denver
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Safety as measured by number of Adverse Events (AEs) by body system
- Status
- Withdrawn
- Last Updated
- last year
Overview
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.
Detailed Description
This trial protocol is designed to evaluate primarily whether the use of sargramostim (recombinant human GM-CSF), administered five days per week (250 μg/m2/day subcutaneously) for four consecutive weeks (20 treatment days), will be well tolerated by and safe for use in young adult participants (age 18-35) with Down Syndrome; Secondarily whether sargramostim will have an impact on cognition, and exploratory whether sargramostim has an impact upon activities of daily and quality of life, and impact upon several biomarkers associated with DS, as evaluated by multimodal neuroimaging techniques and blood analyses.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •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.
Exclusion Criteria
- •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.
- •Vaccination with live attenuated virus within six weeks of inclusion in the study or planned during the study.
- •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).
- •Active cancer / malignant neoplasm within five years of screening other than nonmelanoma skin cancers (e.g., basal cell or squamous cell). Previous diagnosis of leukemia, despite remission state or length of time, is exclusionary.
- •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).
Arms & Interventions
Sargramostim
Sargramostim 250 μg/m2/day subcutaneously (5 days per week)
Intervention: Sargramostim for Injection
Placebo Control - Saline
Placebo equivalent volume subcutaneously (5 days per week)
Intervention: Saline Placebo
Outcomes
Primary Outcomes
Safety as measured by number of Adverse Events (AEs) by body system
Time Frame: Informed consent to Follow-up Visit (20 weeks)
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.
Secondary Outcomes
- Down syndrome Mental Status Exam (DSMSE)(Baseline to End of Treatment, Follow-up (20 weeks))