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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02702180




Registration number
NCT02702180
Ethics application status
Date submitted
28/02/2016
Date registered
8/03/2016

Titles & IDs
Public title
Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis
Scientific title
A Randomised, Double-blind, Placebo-controlled Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis Patients
Secondary ID [1] 0 0
2015-003878-33
Secondary ID [2] 0 0
MOL-PAP-002
Universal Trial Number (UTN)
Trial acronym
IMPALA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autoimmune Pulmonary Alveolar Proteinosis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Molgramostim
Treatment: Drugs - Placebo
Treatment: Devices - PARI eFlow nebulizer system

Experimental: Double-blind molgramostim once daily - Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks

Experimental: Double-blind molgramostim intermittent - Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles)

Placebo comparator: Double-blind placebo - Inhalation of placebo nebuliser solution once daily for 24 weeks

Experimental: Open-label molgramostim intermittent - Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 or 48 weeks from completion of the double-blind period


Treatment: Drugs: Molgramostim
300 mcg molgramostim (rhGM-CSF) nebulizer solution for inhalation

Treatment: Drugs: Placebo
Placebo nebulizer solution for inhalation

Treatment: Devices: PARI eFlow nebulizer system
PARI eFlow nebulizer system
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Absolute Change From Baseline of Alveolar-arterial Oxygen Concentration (A-a(DO2)) After 24 Weeks of Treatment
Timepoint [1] 0 0
From baseline to 24 weeks
Secondary outcome [1] 0 0
Change From Baseline in 6-minute Walking Distance (6MWD) After 24 Weeks of Treatment
Timepoint [1] 0 0
From baseline to 24 weeks
Secondary outcome [2] 0 0
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score After 24 Weeks of Treatment
Timepoint [2] 0 0
From baseline to 24 weeks
Secondary outcome [3] 0 0
Number of Whole Lung Lavage During 24 Weeks of Treatment
Timepoint [3] 0 0
From baseline to 24 weeks
Secondary outcome [4] 0 0
Number of Adverse Events (AEs) During 24 Weeks of Treatment
Timepoint [4] 0 0
From baseline to 24 weeks
Secondary outcome [5] 0 0
Number of Serious Adverse Events (SAEs) During 24 Weeks of Treatment
Timepoint [5] 0 0
From baseline to 24 weeks
Secondary outcome [6] 0 0
Number of Adverse Drug Reactions (ADRs) During 24 Weeks of Treatment
Timepoint [6] 0 0
From baseline to 24 weeks
Secondary outcome [7] 0 0
Number of Severe AEs During 24 Weeks of Treatment
Timepoint [7] 0 0
From baseline to 24 weeks
Secondary outcome [8] 0 0
Number of Participants With at Least 1 AE Leading to Treatment Discontinuation During 24 Weeks of Treatment
Timepoint [8] 0 0
From baseline to 24 weeks

Eligibility
Key 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 2 months prior to the Baseline visit.
* Arterial oxygen tension (PaO2) <75 mmHg/<10 kilo Pascal (kPa) at rest, OR desaturation of >4 percentage points on the 6MWT
* An alveolar-arterial oxygen difference [(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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Diagnosis of hereditary or secondary PAP
* WLL within 1 month of Baseline
* Treatment with GM-CSF within 3 months of Baseline
* Treatment with rituximab within 6 months of Baseline
* Treatment with plasmapheresis within 3 months of Baseline
* Treatment with any investigational medicinal product within 4 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 participant unsuitable for the trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/03/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/09/2019
Sample size
Target
Accrual to date
Final
139
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2050 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
Denmark
State/province [4] 0 0
Aarhus
Country [5] 0 0
France
State/province [5] 0 0
Rennes
Country [6] 0 0
Germany
State/province [6] 0 0
Essen
Country [7] 0 0
Germany
State/province [7] 0 0
Gauting
Country [8] 0 0
Germany
State/province [8] 0 0
Heidelberg
Country [9] 0 0
Germany
State/province [9] 0 0
Lübeck
Country [10] 0 0
Greece
State/province [10] 0 0
Athens
Country [11] 0 0
Israel
State/province [11] 0 0
Peta? Tiqwa
Country [12] 0 0
Italy
State/province [12] 0 0
Pavia
Country [13] 0 0
Japan
State/province [13] 0 0
Niigata
Country [14] 0 0
Japan
State/province [14] 0 0
Osaka
Country [15] 0 0
Japan
State/province [15] 0 0
Sendai
Country [16] 0 0
Japan
State/province [16] 0 0
Toyohashi
Country [17] 0 0
Japan
State/province [17] 0 0
Yokohama
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Netherlands
State/province [19] 0 0
Nieuwegein
Country [20] 0 0
Portugal
State/province [20] 0 0
Lisboa
Country [21] 0 0
Portugal
State/province [21] 0 0
Porto
Country [22] 0 0
Russian Federation
State/province [22] 0 0
St. Petersburg
Country [23] 0 0
Slovakia
State/province [23] 0 0
Vyšné Hágy
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Switzerland
State/province [25] 0 0
Lausanne
Country [26] 0 0
Turkey
State/province [26] 0 0
Istanbul
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Savara Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Cliff Morgan, MD
Address 0 0
Royal Brompton Hospital London
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02702180