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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.
Verified December 2017 by Savara Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02702180
First Posted: March 8, 2016
Last Update Posted: December 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Savara Inc.
  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 intermittently (seven days on, seven days off) 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:
  • Change from baseline in 6-minute walking distance after 24-weeks treatment [ Time Frame: baseline and 24 weeks ]
  • Change from baseline in St. George's respiratory questionnaire total score after 24-weeks treatment [ Time Frame: baseline and 24 weeks ]
  • Time to whole lung lavage during 24-weeks treatment [ Time Frame: 24 weeks ]
  • Number of adverse events during 24-weeks treatment [ Time Frame: during 24 weeks ]
  • Number of serious adverse events during 24-weeks treatment [ Time Frame: during 24 weeks ]
  • Number of adverse drug reactions during 24-weeks treatment [ Time Frame: during 24 weeks ]
  • Number of severe adverse events during 24-weeks treatment [ Time Frame: during 24 weeks ]
  • Number of adverse events leading to treatment discontinuation during 24-weeks treatment [ Time Frame: during 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 dyspnoea and cough scores [ Time Frame: baseline and 24 weeks ]
  • Number of subjects with improved CT score after 24-weeks treatment [ Time Frame: baseline and 24 weeks ]

Estimated Enrollment: 90
Actual Study Start Date: February 2016
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: October 2018 (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 for seven days and placebo nebuliser solution for seven days for 24 weeks (12 cycles)
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 tolerance to exercise, effect on Quality of Life, time to Whole Lung Lavage (WLL), effect on pulmonary function, effect on dyspnea and cough, 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 trial, WLL may be applied as rescue therapy in case of significant clinical worsening. In the Follow-up period, open-label treatment with molgramostim will be provided.

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

Information from the National Library of Medicine

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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 one month 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
  • 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
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): NCT02702180


Contacts
Contact: Mikkel Walmar mikkel.walmar@savarapharma.com
Contact: Cecilia Ganslandt, MD cega@savarapharma.com

  Show 32 Study Locations
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
First Submitted: February 28, 2016
First Posted: March 8, 2016
Last Update Posted: December 12, 2017
Last Verified: December 2017

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