A Phase 3 extension study designed to evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents with severe, uncontrolled asthma on Inhaled Corticosteroids and at least one additional asthma controller

Phase 1

• Conditions: Severe Uncontrolled Asthma; MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2018-002501-53-AT
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-24
• Last Update Posted: 21 September 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 975

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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 65
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 785
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the long-term safety and tolerability of<br>Tezepelumab in severe asthma subjects;Secondary Objective: To assess the long-term effect of 210 mg<br>Tezepelumab SC Q4W on asthma exacerbations in<br>adult and adolescent subjects with severe<br>uncontrolled asthma compared with placebo;Primary end point(s): Exposure adjusted incidence rates of AEs/SAEs;Timepoint(s) of evaluation of this end point: Baseline (Week 0 in predecessor study) to 104 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Annualized asthma exacerbation rate (AAER);Timepoint(s) of evaluation of this end point: Baseline (Week 0 in predecessor study) to 104 weeks