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

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

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.

Study Overview

• Status: Completed
• Conditions: Drug Kinetics; Drug Effects on Physiology
• Intervention / Treatment: Biological: sargramostim

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Mount-Royal, Quebec, Canada, H3P 3P1
      • AltaSciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Partner Therapeutics, Inc.
• Investigators: Study Director: Ila Joshi, PhD, Partner Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2022
• Primary Completion (Actual): May 27, 2022
• Study Completion (Actual): June 16, 2022

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 4, 2022
• First Posted (Actual): May 9, 2022

Study Record Updates

• Last Update Posted (Actual): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 30, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration; Physiological Effects of Drugs; Immunologic Factors; Sargramostim
• Other Study ID Numbers: PTX-001-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes