ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    NCT02702180
Previous Study | Return to List | Next Study

Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (aPAP) (IMPALA)

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.
ClinicalTrials.gov Identifier: NCT02702180
Recruitment Status : Recruiting
First Posted : March 8, 2016
Last Update Posted : April 12, 2018
Sponsor:
Information provided by (Responsible Party):
Savara Inc.

February 28, 2016
March 8, 2016
April 12, 2018
February 2016
March 2019   (Final data collection date for primary outcome measure)
Absolute change from baseline to 24 weeks of Alveolar - arterial oxygen concentration (A-a(DO2)) [ Time Frame: baseline and 24 weeks ]
Same as current
Complete list of historical versions of study NCT02702180 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
 
Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
A Randomised, Double-Blind, Placebo-Controlled Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary AlveoLAr Proteinosis Patients "IMPALA"
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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Autoimmune Pulmonary Alveolar Proteinosis
  • Drug: molgramostim
    molgramostim nebuliser solution
    Other Name: rhGM-CSF
  • Drug: placebo
    placebo nebuliser solution
  • Experimental: molgramostim continuously
    Inhalation of molgramostim nebuliser solution (rhGM-CSF) 300 mcg once daily for 24 weeks
    Intervention: Drug: molgramostim
  • 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)
    Interventions:
    • Drug: molgramostim
    • Drug: placebo
  • Placebo Comparator: placebo
    Inhalation of placebo nebuliser solution once daily for 24 weeks
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
135
51
September 2019
March 2019   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Older Adult)
No
Contact: Mikkel Walmar mikkel.walmar@savarapharma.com
Contact: Cecilia Ganslandt, MD cega@savarapharma.com
Australia,   Denmark,   France,   Germany,   Greece,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Portugal,   Romania,   Russian Federation,   Slovakia,   Spain,   Switzerland,   Turkey,   United Kingdom,   United States
 
 
NCT02702180
MOL-PAP-002
Yes
Not Provided
Not Provided
Savara Inc.
Savara Inc.
Not Provided
Principal Investigator: Cliff Morgan, MD Royal Brompton Hospital London
Savara Inc.
December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP