Clinical Trial Results:
A Multicentre, Randomised, Open-label, Parallel-group, Functionality, and Performance Study of an Accessorised Pre-filled Syringe and Autoinjector with Home-administered Subcutaneous Tezepelumab in Adolescent and Adult Subjects with Severe Asthma (PATH-HOME)
Summary
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EudraCT number |
2018-004588-30 |
Trial protocol |
PL |
Global end of trial date |
05 Jun 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Dec 2020
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First version publication date |
18 Dec 2020
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
D5180C00011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03968978 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
AstraZeneca
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Sponsor organisation address |
151 85, Södertälje, Sweden,
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Public contact |
Global Clinical Head, AstraZeneca, +1 8772409479, information.center@astrazeneca.com
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Scientific contact |
AstraZeneca Clinical Study Information, AstraZeneca, information.center@astrazeneca.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Jul 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Jun 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Jun 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of the study is to assess the successful administration, performance, and functionality of a single-use accessorized pre-filled syringe (APFS) and autoinjector (AI) with a fixed 210 mg dose of tezepelumab administered subcutaneously (SC) in clinic and an at-home setting.
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Protection of trial subjects |
Data safety monitoring board is not utilized for this study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 May 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 37
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Country: Number of subjects enrolled |
Japan: 17
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Country: Number of subjects enrolled |
Poland: 78
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Country: Number of subjects enrolled |
United States: 84
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Worldwide total number of subjects |
216
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EEA total number of subjects |
78
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
24
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Adults (18-64 years) |
152
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From 65 to 84 years |
40
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85 years and over |
0
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Recruitment
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Recruitment details |
266 subjects enrolled in the study. 50 subjects were screen failure, and 216 randomized. | |||||||||||||||
Pre-assignment
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Screening details |
216 subjects randomized to tezepelumab 210 mg Q4W via APFS and tezepelumab 210 mg Q4W via AI. All randomized subjects were treated. 111 (51.4%) were randomized to tezepelumab 210 mg Q4W via APFS and 105 (48.6%) were randomized to tezepelumab 210 mg Q4W via AI. | |||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Teze 210 mg Q4W via APFS | |||||||||||||||
Arm description |
Accessorized pre-filled syringe every 4 weeks administered subcutaneously | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Tezepelumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
210 mg
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Arm title
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Teze 210 mg Q4W via AI | |||||||||||||||
Arm description |
Autoinjector every 4 weeks administered subcutaneously | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Tezepelumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
210 mg
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Baseline characteristics reporting groups
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Reporting group title |
Teze 210 mg Q4W via APFS
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Reporting group description |
Accessorized pre-filled syringe every 4 weeks administered subcutaneously | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Teze 210 mg Q4W via AI
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Reporting group description |
Autoinjector every 4 weeks administered subcutaneously | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Teze 210 mg Q4W via APFS
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Reporting group description |
Accessorized pre-filled syringe every 4 weeks administered subcutaneously | ||
Reporting group title |
Teze 210 mg Q4W via AI
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Reporting group description |
Autoinjector every 4 weeks administered subcutaneously |
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End point title |
Proportions of HCPs and subjects/caregivers who successfully administered tezepelumab in clinic or at home by device type [1] | ||||||||||||||||||||||||||||||
End point description |
Successful administration is defined as an injection completed, based on a used/returned (HCP or subject/caregiver) answer of YES to all 5 questions in the administration questionnaire, and satisfactory in vitro evaluation of returned/evaluated devices.
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End point type |
Primary
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End point timeframe |
Week 0, Week 4, Week 8, Week 12, Week 16, Week 20
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: According to the protocol the primary analysis in this study was not a comparison between treatments, it was to assess the functionality in each treatment arm separately. Therefore no statistical analysis is included in this form. The proportions and confidence intervals within treatment arms are however provided. |
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No statistical analyses for this end point |
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End point title |
Proportions of used/returned devices that pass functional tests and visual inspection and showed no evidence of malfunction | ||||||||||||||||||||||||||||||
End point description |
Devices that passed functional tests and visual inspection and showed no evidence of malfunction will be evaluated as functional.
Percentages have been calculated by using the number of used and returned devices at specified visit as denominator.
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End point type |
Secondary
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End point timeframe |
Week 0, Week 4, Week 8, Week 12, Week 16, Week 20
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No statistical analyses for this end point |
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End point title |
Proportions of devices that have been reported as malfunctioning (Product Complaints) | ||||||||||||||||||||||||||||||
End point description |
Performance is measured by the proportion of APFS or AI devices that have been reported as malfunctioning (i.e. via Product Complaints).
Percentages have been calculated by using the number of used and returned devices at specified visit as denominator.
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End point type |
Secondary
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End point timeframe |
Week 0, Week 4, Week 8, Week 12, Week 16, Week 20
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No statistical analyses for this end point |
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End point title |
Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) score | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The ACQ-6 captures asthma symptoms and short-acting β2-agonist use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.
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End point type |
Secondary
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End point timeframe |
Baseline (Week 0), Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24
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No statistical analyses for this end point |
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End point title |
Serum trough concentrations | ||||||||||||||||||||||||
End point description |
PK serum samples were collected pre-dose on dosing visits
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End point type |
Secondary
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End point timeframe |
Baseline (Week 0), Week 4, Week 20 and Week 24 (EOT)
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No statistical analyses for this end point |
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End point title |
Anti-drug antibodies (ADA) | |||||||||||||||||||||||||||||||||
End point description |
Anti-drug antibodies (ADA) responses at baseline and/or post baseline. Treatment-induced ADA positive is defined as ADA negative at baseline and post-baseline ADA positive. Treatment-boosted ADA positive is defined as baseline positive ADA titre that was boosted to a 4-fold or higher-level following IP administration. Treatment-emergent ADA (TE-ADA) positive is defined as either treatment-induced ADA positive or treatment-boosted ADA positive. ADA incidence is the proportion of TE-ADA positive subjects in a population. Persistently positive is defined as ADA positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive) or ADA positive at last post-baseline assessment. Transiently positive is defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive
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End point type |
Secondary
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End point timeframe |
Pre-treatment on dosing days until end of follow-up (Week 36) per protocol
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From first dose till end of study (Week 36)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Teze 210 mg Q4W via APFS
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Reporting group description |
Accessorized pre-filled syringe every 4 weeks administered subcutaneously | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Teze 210 mg Q4W via AI
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Reporting group description |
Autoinjector every 4 weeks administered subcutaneously | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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03 Jul 2019 |
Added exclusion criterion of non-leukocyte depleted whole blood transfusion in 120 days prior to Visit 1 |
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03 Jul 2019 |
Language was updated from “Prior to the date of randomisation, a history of continuous treatment with medium or high dose ICS plus a second controller medication for at least six months prior to Visit 1 should be documented in source documents and recorded in the eCRF.” to “Prior to the date of randomisation, a history of continuous treatment with medium or high dose ICS for at least six months prior to Visit 1 plus a second controller medication for at least three months prior to Visit 1 should be documented in source documents and recorded in the eCRF.” |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |