E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autoimmune Pulmonary Alveolar Proteinosis (aPAP) |
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E.1.1.1 | Medical condition in easily understood language |
Pulmonary Alveolar Proteinosis, commonly known by the acronym PAP, is a rare lung disease characterized by the build-up of proteinaceous material in the alveoli (air sacs) of the lungs. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037316 |
E.1.2 | Term | Pulmonary alveolar proteinosis |
E.1.2 | System Organ Class | 100000004855 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate safety of long term use of inhaled molgramostim. |
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E.2.2 | Secondary objectives of the trial |
• To investigate effects of long term use of inhaled molgramostim on oxygenation.
• To investigate effects of long term use of inhaled molgramostim on exercise capacity.
• To investigate effects of long term use of inhaled molgramostim on respiratory quality of life.
• To investigate frequency of need for WLL during long term use of inhaled molgramostim.
• To investigate effects of long term use of inhaled molgramostim on lung function.
• To investigate maintenance of effect after discontinuation of inhaled molgramostim. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completer of the IMPALA trial
2. 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 trial treatment. Females of childbearing potential must have a negative urine pregnancy test at Baseline or at start of treatment if treatment is not dispensed at Baseline, and must not be lactating during and until 30 days after last dose of trial treatment.
3. 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 above.
4. Willing and able to provide signed informed consent. |
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E.4 | Principal exclusion criteria |
1. Treatment with GM-CSF products other than molgramostim nebuliser solution within three months of Baseline.
2. Treatment with any IMP other than inhaled molgramostim within four weeks of Baseline.
3. History of allergic reactions to GM-CSF.
4. 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.
5. Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product.
6. History of, or present, myeloproliferative disease or leukaemia.
7. Apparent pre-existing concurrent pulmonary fibrosis.
8. Any other serious medical condition which in the opinion of the investigator would make the subject unsuitable for the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of AEs, SAEs, adverse drug reactions (ADRs), and AEs leading to treatment discontinuation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• (A-a)DO2 during the trial
• 6MWD during the trial
• SGRQ total score during the trial
• Frequency of WLL during the trial
• DLCO (% predicted), FEV1 (% predicted), and FVC (% predicted) during the trial
• PaO2 and disease severity score (DSS) during the trial
• Need for oxygen supplement therapy during the trial
• Number of subjects not requiring treatment for aPAP and time off treatment after discontinuation of inhaled molgramostim |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Denmark |
France |
Germany |
Greece |
Israel |
Italy |
Netherlands |
Russian Federation |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |