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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (Part 1) | Experimental | Single dose of 250 microgram (mcg) sargramostim IV over 2 hours |
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| Cohort 2 (Part 1) | Experimental | Single dose of 25 mcg sargramostim SC |
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| Cohort 3 (Part 1) | Experimental | Single dose of 125 mcg sargramostim SC |
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| Cohort 4 (Part 1) | Experimental | Single dose of 250 mcg sargramostim SC |
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| Cohort 5 (Part 1) | Experimental | Single dose of 500 mcg sargramostim SC |
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| Cohort 6 (Part 1) | Experimental | Single dose of 250 mcg sargramostim IH |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sargramostim | Biological | Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor. |
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| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ila Joshi, PhD | Partner Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AltaSciences | Mount Royal | Quebec | H3P 3P1 | Canada |
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| Cohort 7 (Part 2) | Experimental | Two doses of 500 mg sargramostim SC, weekly |
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| 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 |
| ID | Term |
|---|---|
| C081222 | sargramostim |
| D003115 | Colony-Stimulating Factors |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
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