Evaluation of a Single Dose of Inhaled Sargramostim in Patients With Autoimmune Pulmonary Alveolar Proteinosis

NCT03006146 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: TPSC-110UL1TR001425
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

Autoimmune PAP is a rare lung disease affecting less than 5,000 individuals in US with no FDA-approved pharmacologic therapy. Results from "off-label" use in case reports and clinical studies completed outside of the US indicate that inhaled rhGM-CSF may be a safe and effective thera-py for autoimmune PAP. Preliminary clinical trials of inhaled rhGM-CSF in autoimmune PAP patients show promising results, 62%-96% therapeutic response rate without any identifiable drug-related adverse effects in at least 73 autoimmune PAP patients. However, the pharmacokinetics (PK), pharmacodynamics (PD), optimal dose, and treatment duration to maximize efficacy are unknown. The goal is to begin to address these knowledge gaps for inhaled sargramostim for autoimmune PAP patients with a pilot safety and PK/PD study (TPSC-110). TPSC-110, PharmPAP, which is a self-controlled open-label, phase I study to evaluate the safety, PK, and PD of inhaled sargra-mostim in autoimmune PAP patients. These results will impact the field by 1) confirming existing published data, 2) monitoring the local effects of inhaled sargramostim in autoimmune PAP patients, 3) potentially demonstrating a safe starting dose for a later trial to evaluate the therapeutic efficacy of inhaled sargramostim for autoimmune PAP.

Conditions

Autoimmune Pulmonary Alveolar Proteinosis

Outcome Measures

Primary Outcomes (1)

• Occurrence of any treatment-emergent adverse events and serious adverse events

  Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  1 year

Secondary Outcomes (7)

• Maximum plasma GM-CSF Concentration (Cmax)

  1 year

• Time to maximum plasma GM-CSF concentration (TMax)

  1 year

• GM-CSF Area Under the Curve (AUC)

  1 year

• Half-life of inhaled GM-CSF (t1/2)

  1 year

• Complete cell counts and differentials in blood and BAL fluid

  1 year

Study Arms (1)

Sargramostim

EXPERIMENTAL

Participants will receive a single administration of inhaled sargramostim (either 125 mcg or 250 mcg dose)

Drug: Sargramostim

Interventions

Sargramostim DRUG

Participants will receive a single administration of inhaled sargramostim (either 125 mcg or 250 mcg dose)

Also known as: Leukine, recombinant human GM-CSF

Sargramostim

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• Age ≥ 18 years and ≤ 80 years
• Able to understand and willing to sign a written informed consent document
• Able and willing to use hand held nebulizer
• Able and willing to adhere to study visit schedule and study procedures
• Diagnosis of autoimmune PAP determined by:
• History of a diagnosis of PAP with or without supporting lung histology or BAL/cytology
• and
• Abnormal serum GM-CSF autoantibody test (GMAb ELISA Test)
• and
• Chest CT findings compatible with a diagnosis of autoimmune PAP
• Evidence of impaired GM-CSF signaling demonstrated by an abnormal STAT5 phosphorylation index (STAT5-PI) test measured in heparinized whole blood at the time screening
• A-aDO2 ≥ 15 mm Hg

You may not qualify if:

• Diagnosis of any other PAP-causing disease
• Autoimmune PAP complicated by:
• Severe disease at screening/enrollment (A-aD02\<50)
• Clinically significant pulmonary fibrosis
• History of any clinically significant:
• Other lung disease
• Cardiovascular disease
• Disease requiring use of systemic steroids in past year
• Coagulopathy or other hematologic disease
• Active / serious lung or systemic infection
• Persistent or unexplained fever \>101oF within 2 months of study
• Use of any immunosuppressive medication within 3-6 months of screening
• Women who are pregnant or plan to become pregnant
• History of active tobacco/e-cig/marijuana use
• Concomitant or recent use of specific medicines

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Rare Diseases Clinical Research Network: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (2)

University of California, Los Angeles

Los Altos, California, 90095, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis, Acquired

Interventions

sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Bruce Trapnell

  Children's Hospital Medical Center, Cincinnati

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: December 30, 2016
• Study Start: July 13, 2017
• Primary Completion: June 7, 2021
• Study Completion: June 7, 2021
• Last Updated: August 3, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)