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Trial record 1 of 1 for:    NCT02702180
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Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (aPAP) (IMPALA)

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by Savara Inc.
Sponsor:
Information provided by (Responsible Party):
Savara Inc.
ClinicalTrials.gov Identifier:
NCT02702180
First received: February 28, 2016
Last updated: February 20, 2017
Last verified: February 2017
  Purpose
This study evaluates inhaled molgramostim (recombinant human (rh) Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)) in the treatment of autoimmune pulmonary alveolar proteinosis patients. A third of the patients will receive inhaled molgramostim daily for 24 weeks, a third will receive inhaled molgramostim every other day for 24 weeks and a third will receive inhaled matching placebo for 24 weeks

Condition Intervention Phase
Autoimmune Pulmonary Alveolar Proteinosis Drug: molgramostim Drug: placebo Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-Blind, Placebo-Controlled Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary AlveoLAr Proteinosis Patients "IMPALA"

Resource links provided by NLM:


Further study details as provided by Savara Inc.:

Primary Outcome Measures:
  • Absolute change from baseline to 24 weeks of Alveolar - arterial oxygen concentration (A-a(DO2)) [ Time Frame: baseline and 24 weeks ]

Secondary Outcome Measures:
  • Number of subjects in need of Whole Lung Lavage (WLL) [ Time Frame: 24 weeks ]
  • Time to WLL [ Time Frame: during 24 weeks ]
  • Absolute change from baseline to 24 weeks in Vital Capacity (% predicted) [ Time Frame: baseline and 24 weeks ]

Other Outcome Measures:
  • Change from baseline to 24 weeks in pulmonary function tests [ Time Frame: baseline and 24 weeks ]
  • Change from baseline to 24 weeks in 6 minute walk distance [ Time Frame: baseline and 24 weeks ]
  • Change from baseline to 24 weeks in dyspnoea score [ Time Frame: baseline and 24 weeks ]
  • Change from baseline to 24 weeks in cough score [ Time Frame: baseline and 24 weeks ]
  • Change from baseline to 24 weeks in Quality of Life scores [ Time Frame: baseline and 24 weeks ]
  • Number of treatment-emergent adverse events (AEs), serious AEs, Adverse Drug Reactions and Severe AEs [ Time Frame: 24 weeks ]

Estimated Enrollment: 51
Actual Study Start Date: February 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: molgramostim continuously
Inhalation of molgramostim nebuliser solution (rhGM-CSF) 300 mcg once daily for 24 weeks
Drug: molgramostim
molgramostim nebuliser solution
Other Name: rhGM-CSF
Experimental: molgramostim intermittently
Inhalation of molgramostim nebuliser solution (rhGM-CSF) 300 mcg every other day and placebo nebuliser solution every other day for 24 weeks
Drug: molgramostim
molgramostim nebuliser solution
Other Name: rhGM-CSF
Drug: placebo
placebo nebuliser solution
Placebo Comparator: placebo
Inhalation of placebo nebuliser solution once daily for 24 weeks
Drug: placebo
placebo nebuliser solution

Detailed Description:

The trial is a randomised, double-blind, placebo-controlled multicentre clinical trial investigating efficacy and safety of inhaled molgramostim (rhGM-CSF) in autoimmune pulmonary alveolar proteinosis (aPAP) patients.

The primary objective is efficacy on the Alveolar-arterial oxygen difference after 24-weeks treatment. Secondary objectives are requirement for, and time to, Whole Lung Lavage (WLL), effect on pulmonary function, tolerance to exercise, effect on dyspnea, cough and Quality of Life, and effect on computed tomography (CT) scoring. Number of reported adverse events (AEs), serious AEs, and adverse drug reactions will be monitored.

The trial will include two phases; a Double-blind treatment period consisting of up to eight trial visits (Screening, Baseline, and at Weeks 4,8,12, 16, 20 and 24 after randomisation) and a Follow-up period consisting of up to five trial visits (at Weeks 4, 12, 24, 36 and 48 post-treatment).

In the Double-blind treatment period, eligible subjects will be randomised to treatment for up to 24 weeks with either: 1) inhaled molgramostim (300 µg) once daily, 2) inhaled molgramostim (300 µg) and matching placebo administered intermittently (seven days on and seven days off) or 3) inhaled placebo once daily. During the Double-blind treatment period, WLL may be applied as rescue therapy in case of significant clinical worsening.

Brief risk assessment:

There is currently no approved pharmacological treatment for patients with PAP, and therefore an unmet need for further treatment modalities exists.

Results from pre-clinical studies with inhaled molgramostim nebuliser solution showed the expected pharmacological effects on white blood cell (WBC) populations locally and systemically in line with observed effects after IV administration of molgramostim. No severe, serious or dose-limiting AEs were observed in the first clinical study in humans (MOL-001). The most common AE was cough, which was reported at a similar incidence for the molgramostim nebuliser solution and placebo. Increases of WBC populations in the blood consistent with the known mechanism of action were observed; most of which were considered not clinically significant. Only two cases (total WBC increased and eosinophilia) were reported as AEs. No development of anti-drug antibodies was observed.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • aPAP diagnosed by computed tomography, or by biopsy, or by Broncho Alveolar Lavage (BAL), and by increased GM-CSF autoantibodies in serum.
  • Stable or progressive aPAP during a minimum period of two months prior to the Baseline visit.
  • Arterial oxygen concentration <75 mmHg/<10 kilo Pascal (kPa) at rest, OR desaturation of >4 percentage points on the 6 Minute Walk Test (6MWT)
  • An (A-a)DO2 of minimum 25 mmHg/3.33 kPa
  • Female or male ≥18 years of age
  • 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, vasectomised partner, sexual abstinence), during and until 30 days after last dose of double-blind trial treatment. Females of childbearing potential must have a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at dosing at Baseline (Visit 2) and must not be lactating
  • Males agreeing to use condoms during and until 30 days after last dose of double-blind medication, or males having a female partner who is using adequate contraception as described above
  • Willing and able to provide signed informed consent
  • 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:

  • Diagnosis of hereditary or secondary pulmonary alveolar proteinosis (PAP)
  • WLL within two months of Baseline
  • Treatment with GM-CSF within three months of Baseline
  • Treatment with rituximab within six months of Baseline
  • Treatment with plasmapheresis within three months of Baseline
  • Treatment with any investigational medicinal product within four weeks of Screening
  • Concomitant use of sputum modifying drugs such as carbocysteine or ambroxol
  • History of allergic reactions to GM-CSF
  • Connective tissue disease, inflammatory bowel disease or other autoimmune disorder requiring treatment associated with significant immunosuppression, e.g. more than 10 mg/day systemic prednisolone
  • Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product
  • History of, or present, myeloproliferative disease or leukaemia
  • Significant liver impairment (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >4 times the upper normal limit) or renal impairment (estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73m2) at Screening.
  • Known active infection (viral, bacterial, fungal or mycobacterial)
  • Apparent pre-existing concurrent pulmonary fibrosis
  • Any other serious medical condition which in the opinion of the investigator would make the subject unsuitable for the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02702180

Contacts
Contact: Jessica Jackson jessica.jackson@savarapharma.com
Contact: Cecilia Ganslandt, MD cega@savarapharma.com

Locations
Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark
Contact: Elisabeth Bendstrup, MD, PhD         
Principal Investigator: Elisabeth Bendstrup, MD, PhD         
France
CHU Rennes Hospital Pontchaillou Recruiting
Rennes, France
Contact: Stephane Jouneau, MD         
Principal Investigator: Stephane Jouneau, MD         
Germany
Westdeutsches Lungenzentrum am Universitätsklinikum Essen Recruiting
Essen, Germany
Contact: Francesco Bonella, MD, PhD         
Principal Investigator: Francesco Bonella         
Asklepios Fachkliniken München - Gauting Not yet recruiting
Gauting, Germany, 82131
Contact: Wolfgang Gesierich, MD         
Principal Investigator: Wolfgang Gesierich, MD         
Sub-Investigator: Juliane Herpich, MD         
Thoraxklinik am Universitätsklinikum Heidelberg Recruiting
Heidelberg, Germany
Contact: Simone Hummler, MD         
Principal Investigator: Michael Kreuter, MD         
Sub-Investigator: Simone Hummler, MD         
Universitätsklinikum des Saarlandes Recruiting
Homburg/Saar, Germany
Contact: Sebastian Faehndrich, MD         
Principal Investigator: Robert Bals, MD         
Sub-Investigator: Sebastian Faehndrich, MD         
Greece
Attikon University Hospital Recruiting
Athens, Greece
Contact: Effrosyni Manali, MD         
Principal Investigator: Spyros Papiris, MD         
Israel
Rabin Medical Center Recruiting
Beilinson, Israel
Contact: Mordechai R Kremer, MD         
Principal Investigator: Mordechai R Kremer, MD         
Sub-Investigator: Wand Ori, MD         
Italy
IRCCS Policlinico San Matteo Recruiting
Pavia, Italy
Contact: Ilaria Campo, PhD         
Principal Investigator: Francesca Mariani, MD         
Japan
Tohoku University Hospital Not yet recruiting
Miyagi, Japan
Contact: Makoto Kobayashi, MD         
Principal Investigator: Makoto Kobayashi, MD         
Aichi Medical University Hospital Recruiting
Nagakute, Japan
Contact: Etsuro Yamaguchi, MD         
Principal Investigator: Etsuro Yamaguchi, MD         
Niigata University Medical and Dental Hospital Recruiting
Niigata, Japan
Contact: Ryushi Tazawa, MD         
Principal Investigator: Ryushi Tazawa, MD         
National Hospital Organization Kinki-Chuo Recruiting
Osaka, Japan
Contact: Yoshikazu Inoue, MD         
Principal Investigator: Yoshikazu Inoue         
Kanagawa Cardiovascular and Respiratory Center Recruiting
Yokohama, Japan
Contact: Baba Tomohisa, MD         
Principal Investigator: Baba Tomohisa, MD         
Netherlands
St. Antonius Hospital Recruiting
Nieuwegein, Netherlands
Contact: Marcel Veltkamp, MD         
Principal Investigator: Marcel Veltkamp, MD, PhD         
Russian Federation
City Hospital St. Petersburg Recruiting
St. Petersburg, Russian Federation
Contact: Yulia Ilkovich, MD, PhD         
Principal Investigator: Yulia Ilkovich, MD, PhD         
Spain
Hospital University de Bellvitge (HUB) Recruiting
Barcelona, Spain, 08907
Contact: Maria Molina Molina, MD         
Principal Investigator: Maria Molina Molina, MD         
Switzerland
Centre Hospitalier Universitaire Vaudois Recruiting
Lausanne, Switzerland
Contact: Romain Lazor, MD         
Principal Investigator: Romain Lazor, MD         
United Kingdom
Royal Brompton Hospital Recruiting
London, United Kingdom
Contact: Cliff Morgan, MD         
Principal Investigator: Cliff Morgan, MD         
Sponsors and Collaborators
Savara Inc.
Investigators
Principal Investigator: Cliff Morgan, MD Royal Brompton Hospital London
  More Information

Additional Information:
Responsible Party: Savara Inc.
ClinicalTrials.gov Identifier: NCT02702180     History of Changes
Other Study ID Numbers: MOL-PAP-002
Study First Received: February 28, 2016
Last Updated: February 20, 2017

Additional relevant MeSH terms:
Pulmonary Alveolar Proteinosis
Autoimmune Diseases
Lung Diseases
Respiratory Tract Diseases
Immune System Diseases
Pharmaceutical Solutions
Molgramostim
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 21, 2017