E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic augmentation and maintenance therapy in individuals with alpha1-proteinase inhibitor (A1-PI) deficiency and clinical evidence of emphysema. |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic hereditary, genetic disorder in which there is not enough of this protein to prevent lung damage and is associated with progressive, severe emphysema. |
|
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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001811 |
E.1.2 | Term | Alpha-1 proteinase inhibitor deficiency |
E.1.2 | System Organ Class | 100000004850 |
|
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 the long-term verification of a disease-modifying benefit of Zemaira® on the progression of emphysema, assessed by volume-adjusted lung density, and measured by yearly computed tomography (CT). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the effect of treatment with A1-PI on:
1. change in symptoms score as assessed by Quality of Life (QoL) using the St. George’s Respiratory Questionnaire (SGRQ);
2. the assessment of pulmonary function (ie, forced expiratory volume in 1 second [FEV1] and [FEV1/forced vital capacity{FVC}]);
3. reduction in risk of pulmonary exacerbations assessed by the number and annual rate of exacerbations over the study duration;
4. antigenic and functional serum A1-PI levels in relation to disease progression, body mass index (BMI), safety, and mortality.
5. the safety profile of subjects will be assessed throughout the study.
The safety of Zemaira® will be assessed by the occurrence of adverse events (AEs). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who have completed the 2-year treatment and observation period in the Phase 3/4 Zemaira® CE1226_4001 study and are willing to sign informed consent.
2. Males, and non-pregnant, non-lactating females, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator. |
|
E.4 | Principal exclusion criteria |
1. Individuals residing in the US.
2. Current evidence of alcohol abuse, or abuse of drugs, such as barbiturates, benzodiazepines, amphetamines, cocaine, opioids, and cannabinoids.
3. History of allergy, anaphylactic reaction, or severe systemic response to human plasma derived products, or known mannitol hypersensitivity, or history of prior adverse reaction (AR) to mannitol.
4. Current tobacco smoker (i.e. smoking must be discontinued for at least 6 months prior to study participation).
5. Conditions or behaviors that interfere with attending scheduled study visits, in the opinion of the investigator.
6. History of non-compliance.
7. Administration of any other experimental new drug or participation in an investigation of a marketed product.
8. Inability to perform necessary study procedures. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Variable: Annual Rate of Change in adjusted P15 from CT Scans
The exploratory efficacy variable of primary interest is the annual rate of change, measured by a slope of time and treatment interaction from a mixed effects model, in volume-adjusted lung density. This is assessed by the 15th percentile (P15) of the lung density distribution. The variable of interest is called adjusted P15 measured in g/L. Scans are obtained at total lung capacity (TLC) and functional residual capacity (FRC) inspiration state, and lung volume is assessed for the right, the left, and for both lungs. During the extension study, the CT scans are taken at Month 12 and Month 24 (ie, Month 36 [Visit 5] and Month 48 [Visit 9] when consideration is given to the start of study CE1226_4001). The primary interest of the study will be comparing the annual rate of change in adjusted P15 from CT scans between subjects who had an early start with Zemaira® treatment and subjects who had a late start with treatment over 4 years. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Key Secondary Efficacy Variable: Absolute and % Change in Adjusted P15 from Baseline to Month 48
The absolute and % change from baseline to the Month 48 will be derived using the values of adjusted P15 of the last assessment of CT scans from study CE1226_3001 and the first assessment of CT scans from study CE1226_4001. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 20 |
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 |
Australia |
Canada |
Czech Republic |
Denmark |
Estonia |
Finland |
Germany |
Ireland |
Poland |
Romania |
Sweden |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |