A Multiple Ascending Dose Study of PUL-042 in Stem Cell Transplant Recipients

Study Overview
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Brief Summary
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Subjects with hematologic malignancies or recipients of a first allogenic or autologus hematopoietic stem cell transplant, without any evidence or respiratory infection, will receive 4 doses of PUL-042 Inhalation Solution over a 2 week period. Subjects will be evaluated for tolerability of the drug. If tolerated, dose escalation may occur with up to 4 dose levels tested

Detailed Description
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This is an open-label multiple ascending dose study with a 3+3 study design to examine the safety and tolerability of PUL-042 Inhalation Solution in subjects with hematologic malignancies or recipients of a first allogenic or autologus hematopoietic stem cell transplant. Subjects will receive 4 doses over 2 weeks. Cohort size will be 3 subjects, once 3 subjects have completed treatment and follow-up at a dose level, subject data will be evaluated by an independent data safety monitoring committee prior to dosing additional subjects. The Committee may recommend increasing the dose, maintaining the same dose, or decreasing the dose. Once the maximum dose is determined, there may be up to 6 additional subjects dosed at that level.

Official Title
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An Open-Label, Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of PUL-042 Inhalation Solution in Subjects With Hematologic Malignancies and Recipients of Stem Cell Transplantation

Conditions
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Hematologic Diseases, Stem Cell Transplants

Intervention / Treatment
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* Drug: PUL-042


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with hematologic malignancies or recipients of a first allogeneic or autologous hematopoietic stem cell transplantation and presently clinically stable Pulse oximetry of hemoglobin saturation ≥92% on room air Adult (≥18 years) Spirometry (FEV1 and forced vital capacity [FVC]) ≥80% of predicted value If female, must be either post-menopausal (one year or greater without menses), surgically sterile, or, for female subjects of child-bearing potential who are capable of conception must be: practicing two effective methods of birth control If female, must not be pregnant, plan to become pregnant, or nurse a child during the study and through 30 days after completion of the study If male, must be surgically sterile or willing to practice two effective methods of birth control Ability to understand and give informed consent Exclusion Criteria: Subjects with any evidence of respiratory infection including any signs or symptoms of either a lower respiratory infection (LRI) or upper respiratory infection (URI) Known history of chronic pulmonary disease Subjects who are being treated for fungal, viral, or bacterial pneumonia Exposure to any investigational agent (defined as any agent not approved by the Food and Drug Administration [FDA]) within 30 days prior to the Screening Visit Patients with a relapsed and/or refractory underlying hematologic malignancy HSCT recipients who underwent ex vivo T-cell depletion of the graft, or a mismatched, or cord or haplo identical blood transplantation HSCT recipients with active and/or chronic graft versus host disease Patients on systemic corticosteroids (oral or intravenous) Absolute neutrophil count (ANC) < 1,000 cells/mL Clinically significant bacteremia or fungemia Current smokers or subjects with any history of smoking

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PUL-042<br>PUL-042 Inhalation Solution | Drug: PUL-042<br>* PUL-042 Inhalation Solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in one Second (FEV1) | Evaluation of increasing doses of PUL-042 Inhalation Solution on FEV1 | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum proteomics | Evalution of increasing doses of PUL-042 Inhalation Solution on serum proteomic profile | 3 weeks |