Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Sargramostim Administered Subcutaneously, Intravenously, or by Inhalation

Study Overview
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Brief Summary
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This single center, single ascending dose (SAD) and repeat dose study in healthy adults comprises 2 parts. Part 1 will consist of 6 SAD cohorts, in which different dose levels of sargramostim will be given by intravenous (IV) infusion, subcutaneous (SC) injection, or inhalation (IH) administration. Part 2 will consist of 1 repeat dose cohort in which sargramostim will begiven by SC administration. Blood samples for PK assessment will be collected before and over 24 hours after each study drug administration. Blood samples for PD assessment will be collected before and up to 14 days after drug administration in Part 1, as well as before the first and up to 14 days after the second drug administration in Part 2. Safety and tolerability will be assessed throughout the study. For Cohort 5 of Part 1 only, 3 subjects will provide a CSF sample for PK assessmen tonce after SC drug administration.

Official Title
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Single Ascending Dose and Repeat Dose Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Sargramostim Administered Subcutaneously, by Intravenous Infusion, or by Inhalation in Healthy Adult Subjects

Conditions
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Drug Kinetics, Drug Effects on Physiology

Intervention / Treatment
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* Biological: sargramostim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male and female participants Nonsmoker or ex-smoker Able to provide informed consent and comply with all study procedures Body Mass Index within 18.5-30.0 kilograms/meter squared, inclusive Females of childbearing potential willing to use highly-effective method of birth control. Exclusion Criteria: Females who are pregnant or breastfeeding History of allergic to sargramostim or its excipients, other human GM-CSFs, or other yeast-derived products. History of severe allergic reactions to other drugs. History of or any current medical condition or laboratory finding that may jeopardize completion of the study, present an increased risk to the subject, or compromise interpretation of the study. . Immunization with COVID-19 vaccine within 14 days of the study. Scheduled immunization with COVID-19 vaccine during the study Use of prescription drugs within 28 days of the study or requirement for maintenance drugs during the study. Participation in another investigational drug study within 28 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Part 1)<br>Single dose of 250 microgram (mcg) sargramostim IV over 2 hours | Biological: sargramostim<br>* Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor.<br>* Other names: rhu-GM-CSF;|
| Experimental: Cohort 2 (Part 1)<br>Single dose of 25 mcg sargramostim SC | Biological: sargramostim<br>* Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor.<br>* Other names: rhu-GM-CSF;|
| Experimental: Cohort 3 (Part 1)<br>Single dose of 125 mcg sargramostim SC | Biological: sargramostim<br>* Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor.<br>* Other names: rhu-GM-CSF;|
| Experimental: Cohort 4 (Part 1)<br>Single dose of 250 mcg sargramostim SC | Biological: sargramostim<br>* Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor.<br>* Other names: rhu-GM-CSF;|
| Experimental: Cohort 5 (Part 1)<br>Single dose of 500 mcg sargramostim SC | Biological: sargramostim<br>* Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor.<br>* Other names: rhu-GM-CSF;|
| Experimental: Cohort 6 (Part 1)<br>Single dose of 250 mcg sargramostim IH | Biological: sargramostim<br>* Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor.<br>* Other names: rhu-GM-CSF;|
| Experimental: Cohort 7 (Part 2)<br>Two doses of 500 mg sargramostim SC, weekly | Biological: sargramostim<br>* Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor.<br>* Other names: rhu-GM-CSF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum concentration |  | Blood samples collected up to 24 hours post dose | 
| time to maximum |  | Blood samples collected up to 24 hours post dose | 
| Area under the concentration-time curve (AUC) from time 0 to 24 hours |  | Blood samples collected up to 24 hours post dose | 
| AUC from time 0 to infinity |  | Blood samples collected up to 24 hours post dose | 
| AUC from time 0 to 24 hours/infinity |  | Blood samples collected up to 24 hours post dose | 
| Elimination half-life |  | Blood samples collected up to 24 hours post dose | 
| Clearance |  | Blood samples collected up to 24 hours post dose | 
| Steady state volume of distribution (IV administration only) |  | Blood samples collected up to 24 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events in Part 1 |  | Up to Day 15 in Part 1 | 
| Number of subjects with adverse events in Part 2 |  | Up to Day 22 in Part 2 | 
| Ratio of T-regulatory cells to T-effector cells in the blood. |  | Up to Day 15 in Part 1, up to Day 22 in Part 2 | 
| CD14/CD16/human leukocyte antigen-DR isotype (HLA-DR) absolute cell count |  | Up to Day 15 in Part 1, up to Day 22 in Part 2 |