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

• Status: Completed
• Trial end date: 2021-06-07
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Center for Advancing Translational Science (NCATS); Rare Diseases Clinical Research Network
• Treatments: Molgramostim; Sargramostim

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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