Inhaled GM-CSF Therapy of Autoimmune PAP

NCT00901511 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: FARM7MCPK4Codice Interno 19900508EudraCT 2008-007086-23
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, open-label, long-term, phase 2 study of inhaled granulocyte/macrophage-colony stimulating factor following whole lung lavage therapy in patients with autoimmune pulmonary alveolar proteinosis.

Conditions

Autoimmune Pulmonary Alveolar Proteinosis

Keywords

Whole lung lavage; GM-CSF; Sargramostim; aPAP

Outcome Measures

Primary Outcomes (1)

• Time to Rescue WLL

  Time (in months) between the scheduled baseline WLL (at Study Month 0) and the first administration of an unscheduled rescue WLL (during the 30-months after Study Month 0)

  30 months

Secondary Outcomes (13)

• Number of Patients Requiring a Rescue WLL

  30 months

• Between-Group Difference in Mean Partial Pressure of Oxygen (PaO2)

  30 months

• Between-Group Difference in Mean Alveolar-arterial Difference in Oxygen Concentration (A-aDO2)

  30 months

• Between-Group Difference in Mean Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO)

  30 months

• Between-Group Difference in Mean Vital Capacity (VC)

  30 months

Study Arms (2)

GM-CSF Group

EXPERIMENTAL

Scheduled Baseline WLL: All participants will receive scheduled bilateral WLL at baseline (month 0). GM-CSF induction treatment: All participants will receive inhaled GM-CSF (250 mcg daily, 7 consecutive days every other week for 12 weeks beginning 1 week after the scheduled baseline WLL). Washout period: All participants will not receive inhaled GM-CSF treatment for 4 weeks immediately following GM-CSF induction treatment. GM-CSF maintenance treatment: All participants will receive inhaled GM-CSF (250 mcg daily on days 1 and 3 of every consecutive 14-day period for 6 months beginning 17 weeks after the scheduled baseline WLL). Unscheduled Rescue WLL: Any participant experiencing progression of aPAP lung disease (defined as the disease progression resulting in respiratory failure (PaO2 at rest \<60 mmHg of PaO2 \> 60 mmHg at rest AND desaturation \<90% at rest OR decline in SpO2 of 5% or more during exercise testing) will receive unscheduled rescue WLL.

Procedure: Baseline WLL; Drug: Sargramostim; Procedure: Rescue WLL

Control Group

OTHER

Scheduled Baseline WLL: All participants will receive a scheduled bilateral WLL at baseline (month 0). Unscheduled Rescue WLL: Any participant experiencing progression of aPAP lung disease (defined as the disease progression resulting in respiratory failure (defined by a resting PaO2 \<60 mmHg or \> 60 mmHg and desaturation \<90% at rest or decline in SpO2 of 5% or more during exercise testing) will receive unscheduled rescue WLL.

Procedure: Baseline WLL; Procedure: Rescue WLL

Interventions

Baseline WLL PROCEDURE

Scheduled bilateral WLL

Control Group; GM-CSF Group

Sargramostim DRUG

Inhaled GM-CSF

Also known as: Leukine®, recombinant granulocyte/macrophage-colony stimulating factor

GM-CSF Group

Rescue WLL PROCEDURE

Unscheduled bilateral WLL

Control Group; GM-CSF Group

Eligibility Criteria

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

You may qualify if:

• Female of male 18 years of age or older
• Diagnosis of autoimmune PAP
• Able and willing to provide written informed consent
• Eligible for whole lung lavage determined as the presence of persistent or progressive respiratory failure (PaO2 at rest \< 60 mm Hg) or desaturation \< 90% or \> 5 percentage points during standard exercise

You may not qualify if:

• Diagnosis with secondary PAP, congenital PAP, or hereditary PAP
• Contraindication to whole lung lavage
• Contraindication to administration of inhaled GM-CSF
• Chronic lung disease associated with already existing respiratory failure, such as emphysema or pulmonary fibrosis, chronic heart failure, ischemic heart disease, active pulmonary embolism, progressive cancer, and other severe metabolic conditions

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo

Pavia, PV, 27100, Italy

Location

Related Publications (5)

• Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med. 2003 Dec 25;349(26):2527-39. doi: 10.1056/NEJMra023226. No abstract available.

  PMID: 14695413 BACKGROUND

• Beccaria M, Luisetti M, Rodi G, Corsico A, Zoia MC, Colato S, Pochetti P, Braschi A, Pozzi E, Cerveri I. Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis. Eur Respir J. 2004 Apr;23(4):526-31. doi: 10.1183/09031936.04.00102704.

  PMID: 15083749 BACKGROUND

• Wylam ME, Ten R, Prakash UB, Nadrous HF, Clawson ML, Anderson PM. Aerosol granulocyte-macrophage colony-stimulating factor for pulmonary alveolar proteinosis. Eur Respir J. 2006 Mar;27(3):585-93. doi: 10.1183/09031936.06.00058305.

  PMID: 16507860 BACKGROUND

• Trapnell BC, Inoue Y, Bonella F, Morgan C, Jouneau S, Bendstrup E, Campo I, Papiris SA, Yamaguchi E, Cetinkaya E, Ilkovich MM, Kramer MR, Veltkamp M, Kreuter M, Baba T, Ganslandt C, Tarnow I, Waterer G, Jouhikainen T; IMPALA Trial Investigators. Inhaled Molgramostim Therapy in Autoimmune Pulmonary Alveolar Proteinosis. N Engl J Med. 2020 Oct 22;383(17):1635-1644. doi: 10.1056/NEJMoa1913590. Epub 2020 Sep 7.

  PMID: 32897035 BACKGROUND

• Tazawa R, Ueda T, Abe M, Tatsumi K, Eda R, Kondoh S, Morimoto K, Tanaka T, Yamaguchi E, Takahashi A, Oda M, Ishii H, Izumi S, Sugiyama H, Nakagawa A, Tomii K, Suzuki M, Konno S, Ohkouchi S, Tode N, Handa T, Hirai T, Inoue Y, Arai T, Asakawa K, Sakagami T, Hashimoto A, Tanaka T, Takada T, Mikami A, Kitamura N, Nakata K. Inhaled GM-CSF for Pulmonary Alveolar Proteinosis. N Engl J Med. 2019 Sep 5;381(10):923-932. doi: 10.1056/NEJMoa1816216.

  PMID: 31483963 BACKGROUND

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis, Acquired

Interventions

sargramostim; 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

Results Point of Contact

• Title: Francesca Mariani
• Organization: Fondazione IRCCS Policlinico San Matteo Pavia

fr.mariani@smatteo.pv.it

+39 0382 503590

Study Officials

• Francesca Mariani, MD

  Fondazione IRCCS Policlinico San Matteo

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study coordinator

Study Record Dates

• First Submitted: May 11, 2009
• First Posted: May 13, 2009
• Study Start: July 1, 2009
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: July 12, 2024
• Results First Posted: June 26, 2023

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)