E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alpha-1 Antitrypsin (AAT) deficiency |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001806 |
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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 |
The objective of this clinical trial is to study the safety and tolerability of Alpha-1 MP in adult Alpha-1 antitrypsin deficient subjects as reported over 20 weeks of therapy. The primary objective is to describe the nature and frequency of treatment-emergent adverse events with “treatment-emergent” defined as any adverse event occurring after the start of the first study drug infusion. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Documented diagnosis of congenital Alpha1-antitrypsin deficiency with genotype being PiZZ, PiZ(null), Pi(null)(null), or “At-risk” alleles as listed in Appendices 10.3. of the Study Protocol. The subject’s genotype must be documented by and/or verifiable through the Alpha-1 Antitrypsin Genetics Laboratory database located in Gainesville, Florida. If a subject's genotype is not documented and or verifiable by the Alpha-1 Antitrypsin Genetics Laboratory, the subject will be required, at screening to provide an additional blood sample (two 10-mL EDTA tubes)for analysis by the Alpha-1 Antitrypsin Genetics Laboratory. This analysis will include genotyping, and if the subject is treatment-naïve, a baseline serum Alpha-1 Proteinase Inhibitor level.
2. Documented Alpha-1 Proteinase Inhibitor serum levels <11uM prior to receiving any augmentation. For naïve subjects, the Alpha 1 Laboratory will also perform a screening Alpha1-Proteinase Inhibitor serum level to determine if the subjects meet this criteria. For those subjects entering the subject that are currently receiving augmentation therapy, historical data obtained at the time the subject was diagnosed with AAT deficiency will be used as verification of meeting this criteria.
3. Documented FEV1 between 20% - 80% of predicted value within last 6 months.
4. Either male or female age ≥ 18 years
5. Written informed consent |
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E.4 | Principal exclusion criteria |
The following exclusion criteria must be evaluated at screening: 1. Diagnosis of liver cirrhosis;
2. Severe concomitant disease (e.g. congestive heart failure (NYHA III/IV), clinically significant pulmonary fibrosis, serious malignant disease);
3. Females who are pregnant, breast feeding, or if of child-bearing potential, unwilling to practice adequate contraception throughout the study;
4. Within the last month prior to study entry, participation in another clinical study if the subject received any investigational product during his/her participation in the investigational study.
5. History of anaphylaxis or severe systemic response to plasma-derived Alpha1-Proteinase Inhibitor or other blood product(s);
6. Use of systemic steroids within the 2 weeks prior to receiving study treatment (this does not include the use of inhaled steroids). Self-limited therapy with systemic steroids to treat an adverse event is not cause to discontinue or disrupt Alpha-1 PI therapy unless, in the opinion of the investigator, this action is warranted. The study’s Medical Monitor should be consulted if the subject requires frequent (>2) self-limited courses of systemic steroids or if long-term therapy is warranted during the subject’s participation in the study.
7. Known selective IgA deficiency
8. Mentally challenged adult subjects who cannot give independent informed consent;
9. Subjects who have had exacerbations of their disease within one month of trial entry; |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to describe the nature and frequency of treatment-emergent adverse events with “treatment-emergent” defined as any adverse event occurring after the start of the first study drug infusion. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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last visit of the last subject |
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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 | 1 |
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 | 1 |