Clinical Trial Results:
Effects of anti-TSLP on airway hyperresponsiveness and mast cell phenotype in asthma
- A randomized double-blind, placebo-controlled trial of MEDI9929
The UPSTREAM study
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Summary
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EudraCT number |
2015-005542-56 |
Trial protocol |
DK |
Global end of trial date |
14 Nov 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Aug 2021
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First version publication date |
06 Aug 2021
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Other versions |
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Summary report(s) |
UPSTREAM trial ERJ 2021 |
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 |
ESR-15-10870
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02698501 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bispebjerg Hospital, lungemedicinsk afdeling
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Sponsor organisation address |
Ebba Lunds vej 48, København NV, Denmark, 2400
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Public contact |
Asger Sverrild, Copenhagen University Hospital Bispebjerg, 45 35313569, asger.sverrild@regionh.dk
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Scientific contact |
Asger Sverrild, Copenhagen University Hospital Bispebjerg, 45 35313569, asger.sverrild@regionh.dk
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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 |
01 Apr 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Aug 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Nov 2019
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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 |
To investigate whether airway hyperresponsiveness to mannitol decreases in response to treatment with MEDI9929 in patients with asthma
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Protection of trial subjects |
Serial ECGs, physical examinations, blood samples, vital parameters and systematic collection of information on any adverse event
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Background therapy |
Inhaled corticosteroids +/- long-acting beta2-agonists +/- leucotriene receptor modifiers +/- long-acting muscarinic antagonists | ||
Evidence for comparator |
According to Global Initiative for Asthma (GINA), the selected group of patients on GINA-step 2-to-4 would otherwise have to be treated with the above mentioned background therapy | ||
Actual start date of recruitment |
01 Apr 2016
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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 |
Denmark: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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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) |
0
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Adults (18-64 years) |
35
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited through advertisement in newspapers and online as well as through advertising in the outpatient clinic. | |||||||||||||||
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Pre-assignment
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Screening details |
84 were assessed for eligibility | |||||||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Assessor | |||||||||||||||
Blinding implementation details |
Independent pharmacists at The Hospital Pharmacy at the Capital Region of Denmark dispensed either placebo or tezepelumab according to a computer-generated randomisation list (www.randomization.com). The allocation sequence was blinded from all staff at the study site and was kept in envelopes with aluminium foil inside to render the envelope impermeable to intense light. Patients, investigators, and study site staff, laboratory technicians responsible for processing samples were blinded.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Active - tezepelumab | |||||||||||||||
Arm description |
intravenous tezepelumab 700 mg in 100ml 5% dextrose | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
tezepelumab
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Investigational medicinal product code |
MEDI9929 anti-TSLP mAb (AMG157)
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
700mg administered over 60 minutes
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Arm title
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Placebo | |||||||||||||||
Arm description |
intravenous placebo in 100ml 5% dextrose | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
5% dextrose
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Investigational medicinal product code |
5% dextrose
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
100ml administered over 60 minutes
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Baseline characteristics reporting groups
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Reporting group title |
Active - tezepelumab
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Reporting group description |
intravenous tezepelumab 700 mg in 100ml 5% dextrose | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
intravenous placebo in 100ml 5% dextrose | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Active - tezepelumab
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Reporting group description |
intravenous tezepelumab 700 mg in 100ml 5% dextrose | ||
Reporting group title |
Placebo
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Reporting group description |
intravenous placebo in 100ml 5% dextrose | ||
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End point title |
Change in PD15 to inhaled mannitol from baseline to week-12 | ||||||||||||
End point description |
change in PD15 (expressed as doubling doses) to inhaled mannitol from baseline to week-12
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End point type |
Primary
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End point timeframe |
12 weeks
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Statistical analysis title |
change in PD15 from baseline to week-12 | ||||||||||||
Statistical analysis description |
mean change in log2 PD15 from baseline to week-12 adjusting for baseline log2PD15 and ICS (high/low)
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Comparison groups |
Active - tezepelumab v Placebo
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.06 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Number of mannitol test negative at week-12 | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 weeks
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Statistical analysis title |
Number of negative tests at week-12 | |||||||||
Statistical analysis description |
the number of subjects who achieved a negative mannitol test (PD15 >635mg) at week-12
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Comparison groups |
Active - tezepelumab v Placebo
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.04 | |||||||||
Method |
Chi-squared | |||||||||
Confidence interval |
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End point title |
Ratio between geometric means - eosinophils | ||||||||||||
End point description |
change in airway tissue eosinophils from baseline to week-12
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End point type |
Secondary
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End point timeframe |
12 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Ratio between geometric means - mast cells | ||||||||||||
End point description |
Change in airway tissue mast cells from baseline to week-12
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End point type |
Secondary
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End point timeframe |
12 weeks
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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 signing informed consent to last visit
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
2020
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Reporting groups
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Reporting group title |
placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
tezepelumab
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/34049943 |
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