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Trial record 1 of 1 for:    IMPALA-2 | Autoimmune Pulmonary Alveolar Proteinosis
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Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP) (IMPALA-2)

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ClinicalTrials.gov Identifier: NCT04544293
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : June 1, 2021
Sponsor:
Information provided by (Responsible Party):
Savara Inc.

Brief Summary:
160 subjects with autoimmune pulmonary alveolar proteinosis (aPAP) will be randomized to receive once daily treatment with inhaled molgramostim or placebo for 48 weeks. Subjects completing the 48 week placebo-controlled period will receive open-label treatment with once daily inhaled molgramostim for 48 weeks.

Condition or disease Intervention/treatment Phase
Autoimmune Pulmonary Alveolar Proteinosis Drug: Molgramostim Drug: Placebo Phase 3

Detailed Description:

This is an interventional, randomized, double-blind, 2-arm, parallel groups, placebo-controlled, multi-center, phase 3 trial in adult subjects who are diagnosed with aPAP.

160 adult subjects with aPAP will be randomized to receive treatment with inhaled molgramostim or placebo.

Autoimmune pulmonary alveolar proteinosis (aPAP) diagnosis should be confirmed by an anti-GM-CSF auto-antibody test result, and history of PAP based on either high resolution computed tomography, lung biopsy, or bronchoalveolar lavage cytology, should be available.

The trial consists of a 6-week screening period, a 48-week randomized, double-blind treatment period, a 48-week open-label treatment period, and a conditional 2-week safety follow-up period. The total treatment duration will be 96 weeks. Subjects who complete the double-blind treatment period will continue into the open-label treatment period and receive once daily treatment with molgramostim. During the trial, whole lung lavage will be allowed as rescue treatment in case of worsening of aPAP.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subject will be randomized 1:1 to treatment with inhaled molgramostim or placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Clinical Trial of Once-daily Inhaled Molgramostim Nebulizer Solution in Adult Subjects With Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
Estimated Study Start Date : July 2021
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Molgramostim
Double-blind treatment with molgramostim nebulizer solution 300 µg once daily for 48 weeks, followed by open-label treatment with molgramostim nebulizer solution 300 µg once daily for 48 weeks
Drug: Molgramostim
Molgramostim 300 µg nebulizer solution
Other Name: Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF)

Placebo Comparator: Placebo
Double-blind treatment with placebo nebulizer solution once daily for 48 weeks, followed by open-label treatment with molgramostim nebulizer solution 300 µg once daily for 48 weeks
Drug: Molgramostim
Molgramostim 300 µg nebulizer solution
Other Name: Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF)

Drug: Placebo
Matching placebo




Primary Outcome Measures :
  1. Change from baseline in % predicted diffusing capacity of the lung for carbon monoxide (DLCO) [ Time Frame: Week 24 ]

Secondary Outcome Measures :
  1. Change from baseline in St. Georges Respiratory Questionnaire Total score [ Time Frame: Week 24 ]
  2. Change from baseline in St. Georges Respiratory Questionnaire Activity component score [ Time Frame: Week 24 ]
  3. Change from baseline in exercise capacity, expressed as peak metabolic equivalents (METs) [ Time Frame: Week 24 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject must be ≥18 years of age, at the time of signing the informed consent.
  2. A serum anti-GM-CSF autoantibody test result confirming autoimmune PAP.
  3. History of PAP, based on examination of a lung biopsy, bronchoalveolar lavage (BAL) cytology, or a high-resolution computed tomogram (HRCT) of the chest.
  4. DLCO 70% predicted or lower at the screening and baseline visits.
  5. Change in % predicted DLCO of <15% points during the screening period.
  6. Demonstrated functional impairment in the treadmill exercise test (defined as a peak MET ≤8).
  7. Willing and able to come off supplemental oxygen use prior to and during the treadmill exercise test, the DLCO assessment, and the arterial blood gas sampling.
  8. Resting SpO2 >85% during 15 minutes without use of supplemental oxygen at the screening visits.
  9. Male or female
  10. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

    1. Male subjects: Males agreeing to use condoms during and until 30 days after last dose of trial treatment, or males having a female partner who is using adequate contraception as described below.
    2. Female subjects: Females who have been post-menopausal for >1 year, or females of childbearing potential after a confirmed menstrual period using a highly efficient method of contraception (i.e. a method with <1% failure rate such as combined hormonal contraception, progesterone-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence*), during and until 30 days after last dose of trial treatment. Females of childbearing potential must have a negative serum pregnancy test at the screening visits, and a negative urine pregnancy test at Baseline visit (Visit 3) and must not be lactating.
  11. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures specified in the protocol as judged by the Investigator.

Exclusion Criteria:

  1. Diagnosis of hereditary or secondary PAP, or a metabolic disorder of surfactant production.
  2. WLL performed within 3 months prior to baseline.
  3. Requirement for WLL at screening or baseline.
  4. GM-CSF treatment within 6 months prior to baseline.
  5. Treatment with rituximab within 6 months prior to baseline.
  6. Treatment with plasmapheresis within 6 weeks prior to baseline.
  7. Treatment with any investigational medicinal product within 5 half-lives or 3 months (whichever is longer) prior to baseline.
  8. Previously randomized in this trial.
  9. History of allergic reactions to GM-CSF or any of the excipients in the nebulizer solution.
  10. Inflammatory or autoimmune disease of a severity that necessitates significant (e.g. more than 10 mg/day systemic prednisolone) immunosuppression.
  11. Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product.
  12. History of, or present, myeloproliferative disease or leukemia.
  13. Apparent pre-existing concurrent pulmonary fibrosis.
  14. Acute or unstable cardiac or pulmonary disease that may be aggravated by exercise.
  15. Known active infection (viral, bacterial, fungal, or mycobacterial) that may affect the efficacy evaluation in the trial.
  16. Physical disability or other condition that precludes safe and adequate exercise testing.
  17. Any other serious medical condition which in the opinion of the Investigator would make the subject unsuitable for the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04544293


Contacts
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Contact: Dhaval Desai, MD +1 (512) 851-1373 info@savarapharma.com
Contact: Badrul Chowdhury +1 (512) 614-1848 info@savarapharma.com

Locations
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United States, Colorado
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Contact: Jami Henriksen    303-398-1233    HenriksenJ@njhealth.org   
United States, Florida
University of Florida Health Recruiting
Gainesville, Florida, United States, 32608
Contact: Erin Silverman    352-273-5870    erin.silverman@medicine.ufl.edu   
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Janine Reveniq    404-778-5737    janine.fennell@emoryhealthcare.org   
Romania
Institutul de Pneumologie M.Nasta Recruiting
Bucarest, Romania, 20021
Contact: Anca Marci       ancamacri@yahoo.com   
Sponsors and Collaborators
Savara Inc.
Investigators
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Principal Investigator: Bruce Trapnell, Prof Children's Hospital Medical Center, Cincinnati
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Responsible Party: Savara Inc.
ClinicalTrials.gov Identifier: NCT04544293    
Other Study ID Numbers: SAV006-05
2020-001263-85 ( EudraCT Number )
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: June 1, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Alveolar Proteinosis
Autoimmune Diseases
Lung Diseases
Respiratory Tract Diseases
Immune System Diseases
Molgramostim
Sargramostim
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents