E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Uncontrolled Asthma |
|
E.1.1.1 | Medical condition in easily understood language |
Severe Asthma |
Schweres Asthma |
|
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 | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of Tezepelumab in severe asthma subjects |
|
E.2.2 | Secondary objectives of the trial |
To assess the long-term effect of 210 mg Tezepelumab SC Q4W on asthma exacerbations in adult and adolescent subjects with severe uncontrolled asthma compared with placebo |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Provision of signed and dated informed consent form prior to any mandatory study specific procedures, sampling and analysis.
2) Negative urine pregnancy test for female subjects of childbearing potential prior to administration of IP at visit 1
3) Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from screening and must agree to continue using such precautions for 16 weeks after the final dose of IP.
4) Inclusion criterion #4 removed with version 2.0 of the clinical study protocol.
5) Subjects who have not met investigational product discontinuation criteria and have attended the EOT visit in either predecessor study D5180C00007 or D5180C00009. Subjects with inadequate compliance with investigational product, assessed at the discretion of the sponsor, might not be randomized.
To enter the extended follow-up phase of the study, the following inclusion criteria also apply:
6) Provision of signed and dated Addendum for Extended Follow-up to Informed Consent, as well as assent by adolescent subjects where applicable, prior to any mandatory study specific procedures, sampling and analyses before Extended Follow Up.
7) Subjects who rollover from D5180C00007 study and in DESTINATION have completed IP dosing to Week 100, have not met IP Discontinuation criteria and have attended the study EOT Visit. Note: If a subject is not able to attend an on-site EOT visit (Week 104) due to COVID-19 can still participate in the Extended Follow-up.
|
|
E.4 | Principal exclusion criteria |
1) Any clinically important pulmonary disease other than asthma
2) Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator
3) Any history of chronic alcohol or drug abuse within 12 months prior to Visit 1
4) Current malignancy or malignancy that developed during a predecessor study
5) Treatment with the following medications within the last 12 weeks prior to randomization: Systemic immunosuppressive/immunomodulating drugs except for OCS used for the treatment of asthma
6) Any important protocol deviations in either of the predecessor studies
7) Pregnant, breastfeeding, or lactating women
To enter the extended follow up phase of the study, the following exclusion criteria also apply: 8) Discontinuation of IP during the treatment period of DESTINATION. 9) Entered DESTINATION from D5180C00009
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Exposure adjusted incidence rates of AEs/SAEs |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline (Week 0 in predecessor study) to 104 weeks |
|
E.5.2 | Secondary end point(s) |
Annualized asthma exacerbation rate (AAER) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline (Week 0 in predecessor study) to 104 weeks |
|
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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Patients who complete treatment period on IMP in D5180C00007 or D5180C00009 |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
Argentina |
Australia |
Austria |
Brazil |
Canada |
France |
Germany |
Israel |
Korea, Republic of |
Poland |
Russian Federation |
Saudi Arabia |
South Africa |
Taiwan |
Turkey |
Ukraine |
United States |
Vietnam |
|
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
|
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |