Clinical Trial Results:
A randomized, double-blind, placebo-controlled, parallel-group, 12-week Proof-of-Concept study to assess the efficacy, safety, and tolerability of rilzabrutinib in participants with moderate-to-severe asthma who are not well controlled on inhaled corticosteroid plus long-acting β2 adrenergic agonist therapy
Summary
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EudraCT number |
2021-002490-26 |
Trial protocol |
ES PL HU BG |
Global end of trial date |
28 Feb 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Mar 2025
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First version publication date |
15 Mar 2025
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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 |
ACT17208
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05104892 | ||
WHO universal trial number (UTN) |
U1111-1262-2956 | ||
Sponsors
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Sponsor organisation name |
Sanofi aventis recherche & développement
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Sponsor organisation address |
82 Avenue Raspail, Gentilly, France, 94250
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.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 |
13 May 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Feb 2024
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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 evaluate the effects of rilzabrutinib compared to placebo on reducing the incidence of “loss of asthma control” (LOAC) events.
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Protection of trial subjects |
Participants were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the participant and considering the local culture. During the course of the trial, participants were provided with individual participant cards indicating the nature of the trial the participant is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the law governing personal data protection in force in all countries in which it operates.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Dec 2021
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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 |
Argentina: 58
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Country: Number of subjects enrolled |
Bulgaria: 50
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Chile: 26
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Country: Number of subjects enrolled |
Hungary: 10
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Country: Number of subjects enrolled |
Korea, Republic of: 6
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Country: Number of subjects enrolled |
Mexico: 4
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Country: Number of subjects enrolled |
Poland: 15
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Country: Number of subjects enrolled |
Romania: 17
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Country: Number of subjects enrolled |
Spain: 5
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Country: Number of subjects enrolled |
Türkiye: 2
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Country: Number of subjects enrolled |
Ukraine: 1
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Country: Number of subjects enrolled |
United Kingdom: 1
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Worldwide total number of subjects |
196
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EEA total number of subjects |
97
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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) |
170
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From 65 to 84 years |
26
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 48 centers in 13 countries. A total of 310 participants were screened between 12 December 2021 and 14 November 2023, of which 114 were screen failures. Screen failures were mainly due to not meeting the eligibility criteria. | ||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 196 participants were randomized. Randomization was stratified by immunoglobulin E levels [(IgE) <100 international units per milliliter (IU/mL) or >=100 IU/mL] and region. Assignment to arms was done centrally using interactive response technology (IRT) in 1:1 ratio. | ||||||||||||||||||||||||||||||||||||||||
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 |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Data analyst, Assessor | ||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo BID | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants were administered placebo orally twice daily (BID) on Day 1 for 12 weeks, added to background therapy of inhaled corticosteroids/long-acting beta 2-adrenergic agonist (ICS/LABA) fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered placebo orally BID, with or without food starting on Day 1.
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Investigational medicinal product name |
Salmeterol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants were administered 1 puff via DPI or 2 puffs via MDI at a stable dose until Week 4.
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Investigational medicinal product name |
Fluticasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants were administered 1 puff via dry powder inhaler (DPI) or 2 puff via metered dose inhaler (MDI) up to Week 9 and gradually withdrawn from Week 6.
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Arm title
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Rilzabrutinib 400 mg BID | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants were administered rilzabrutinib 400 milligram (mg) orally BID on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Rilzabrutinib
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Investigational medicinal product code |
SAR444671
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Other name |
PRN1008
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered rilzabrutinib orally BID, with or without food starting on Day 1.
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Investigational medicinal product name |
Salmeterol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants were administered 1 puff via DPI or 2 puffs via MDI at a stable dose until Week 4.
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Investigational medicinal product name |
Fluticasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants were administered 1 puff via DPI or 2 puff via MDI up to Week 9 and gradually withdrawn from Week 6.
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Arm title
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Placebo TID | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants were administered placebo orally three times a day (TID) on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered placebo orally TID, with or without food starting on Day 1.
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Investigational medicinal product name |
Salmeterol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants were administered 1 puff via DPI or 2 puffs via MDI at a stable dose until Week 4.
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Investigational medicinal product name |
Fluticasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants were administered 1 puff via DPI or 2 puff via MDI up to Week 9 and gradually withdrawn from Week 6.
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Arm title
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Rilzabrutinib 400 mg TID | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants were administered rilzabrutinib 400 mg orally TID on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Rilzabrutinib
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Investigational medicinal product code |
SAR444671
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Other name |
PRN1008
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered rilzabrutinib orally TID, with or without food starting on Day 1.
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Investigational medicinal product name |
Salmeterol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants were administered 1 puff via DPI or 2 puffs via MDI at a stable dose until Week 4.
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Investigational medicinal product name |
Fluticasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants were administered 1 puff via DPI or 2 puff via MDI up to Week 9 and gradually withdrawn from Week 6.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo BID
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Reporting group description |
Participants were administered placebo orally twice daily (BID) on Day 1 for 12 weeks, added to background therapy of inhaled corticosteroids/long-acting beta 2-adrenergic agonist (ICS/LABA) fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rilzabrutinib 400 mg BID
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Reporting group description |
Participants were administered rilzabrutinib 400 milligram (mg) orally BID on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo TID
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Reporting group description |
Participants were administered placebo orally three times a day (TID) on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rilzabrutinib 400 mg TID
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Reporting group description |
Participants were administered rilzabrutinib 400 mg orally TID on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo BID
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Reporting group description |
Participants were administered placebo orally twice daily (BID) on Day 1 for 12 weeks, added to background therapy of inhaled corticosteroids/long-acting beta 2-adrenergic agonist (ICS/LABA) fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||
Reporting group title |
Rilzabrutinib 400 mg BID
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Reporting group description |
Participants were administered rilzabrutinib 400 milligram (mg) orally BID on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||
Reporting group title |
Placebo TID
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Reporting group description |
Participants were administered placebo orally three times a day (TID) on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||
Reporting group title |
Rilzabrutinib 400 mg TID
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Reporting group description |
Participants were administered rilzabrutinib 400 mg orally TID on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. |
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End point title |
Percentage of Participants With an Loss of Asthma Control (LOAC) Event | ||||||||||||||||||||
End point description |
An LOAC event was a deterioration of asthma defined as any of the following:
A 30% or greater reduction from baseline in morning peak expiratory flow (PEF) on 2 consecutive days.
>= 6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in 24 hours (compared to baseline) on 2 consecutive days.
Increase in inhaled corticosteroid (ICS) >= 4 times the last prescribed ICS dose.
Required use of systemic (oral and/or parenteral) steroid treatment.
Required hospitalization or emergency room visit for asthma exacerbation.
The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier.
The modified intent-to-treat (mITT) included all randomized participants who received at least 1 dose of study treatment analyzed according to the treatment group allocated by randomization.
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End point type |
Primary
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End point timeframe |
Up to Week 12
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Statistical analysis title |
Placebo BID versus rilzabrutinib BID | ||||||||||||||||||||
Statistical analysis description |
Derived from logistic regression with study treatment group, baseline IgE strata level, region (Latin America versus Rest of the world in BID cohort), and number of exacerbation events within 2 years prior to screening.
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Comparison groups |
Placebo BID v Rilzabrutinib 400 mg BID
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Number of subjects included in analysis |
64
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.288 | ||||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||||
Point estimate |
0.57
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Confidence interval |
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level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.202 | ||||||||||||||||||||
upper limit |
1.608 | ||||||||||||||||||||
Statistical analysis title |
Placebo TID versus rilzabrutinib TID | ||||||||||||||||||||
Statistical analysis description |
Derived from logistic regression with study intervention group, baseline IgE strata level, region (Eastern Europe versus Rest of the world in TID cohort), and number of exacerbation events within 2 years prior to screening.
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Comparison groups |
Placebo TID v Rilzabrutinib 400 mg TID
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Number of subjects included in analysis |
132
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.2083 | ||||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||||
Point estimate |
0.584
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Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.253 | ||||||||||||||||||||
upper limit |
1.349 |
|
|||||||||||||||||||||
End point title |
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in one Second (FEV1) at Week 12 | ||||||||||||||||||||
End point description |
Spirometry is a standard test to measure the participant’s lung function. It was performed in accordance with the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration. Spirometry was performed in the morning. The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier. The mITT included all randomized participants who received at least 1 dose of study treatment analyzed according to the treatment group allocated by randomization. Only participants with data collected at Baseline and Week 12 are reported.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Week 12
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in one Second at Week 12 | ||||||||||||||||||||
End point description |
Spirometry is a standard test to measure the participant’s lung function. It was performed in accordance with the ATS/ERS guidelines. The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. After the measurement of pre-bronchodilator FEV1, participants received 2-4 puffs of albuterol/salbutamol or levalbuterol/levosalbutamol. Post- bronchodilator FEV1 referred to the spirometry performed within 30 minutes after administration of bronchodilator. The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier. The mITT included all randomized participants who received at least 1 dose of study treatment analyzed according to the treatment group allocated by randomization. Only participants with data collected at Baseline and Week 12 are reported.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Week 12
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Pre-Bronchodilator and Post-Bronchodilator Forced Expiratory Volume in one Second Over Time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Spirometry is a standard test to measure the participant’s lung function. It was performed in accordance with the ATS/ERS guidelines. The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry was performed in morning. After the measurement of pre-bronchodilator FEV1, participants received 2-4 puffs of albuterol/salbutamol or levalbuterol/levosalbutamol. Post- bronchodilator FEV1 referred to the spirometry performed within 30 minutes after administration of bronchodilator. The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier. mITT included all randomized participants who received at least 1 dose of study treatment analyzed. Only n=number of participants with data collected at specified times for specified categories are reported. 9999 indicates no participants evaluated at specified timepoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Weeks 2, 4, 6, 8, and 10
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Change from Baseline in the Percent Predicted Forced Expiratory Volume in one Second at Week 12 (Pre-Bronchodilator and Post-Bronchodilator) | ||||||||||||||||||||||||||||||
End point description |
Spirometry is a standard test to measure the participant’s lung function. It was performed in accordance with the ATS/ERS guidelines. The FEV1 was the volume of air exhaled from the lungs in first second of a forced expiration as measured by spirometer. Spirometry was performed in the morning. After the measurement of pre-bronchodilator FEV1, participants received 2-4 puffs of albuterol/salbutamol or levalbuterol/levosalbutamol. Post-bronchodilator FEV1 referred to spirometry performed within 30 minutes after administration of bronchodilator. Percent predicated FEV1 for pre and post bronchodilator is reported. The baseline is defined as the available value on the latest date up to randomization date or the first double-blind study treatment date whichever occurs earlier. The mITT included all randomized participants who received at least 1 dose of study treatment analyzed. Only n=number of participants with data collected at specified times for specified categories are reported.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Week 12
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in the Forced Vital Capacity (FVC) Over Time | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Spirometry is a standard test to measure the participant’s lung function. It was performed in accordance with the ATS/ERS guidelines. FVC measures the total volume of air that a participant can breathe out forcefully from a full breath, blowing all of it out. The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier. The mITT included all randomized participants who received at least 1 dose of study treatment analyzed according to the treatment group allocated by randomization. Only participants with data collected at specified times are reported. Here, n=number of participants with data collected for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Weeks 2, 4, 6, 8, 10, and 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in the Peak Expiratory Flow (PEF) Over Time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
PEF is defined as participant’s maximum speed of expiration as measured with electronic PEF meter. AM PEF was performed within 15 minutes after arising and PM PEF was performed in the evening. Baseline AM PEF is the mean AM measurement recorded for the 7 days prior to the first dose of study treatment, and baseline PM PEF is the mean PM measurement recorded for the 7 days prior to the first dose of study treatment. The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier. The mITT population. Only participants with data collected at specified times are reported. Here, n=number of participants with data collected for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Forced Expiratory Flow [(FEV) 25-75%] Over Time | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Spirometry is a standard test to measure the participant’s lung function. It was performed in accordance with the ATS/ERS guidelines. FEF is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the FEF at 25% to 75% of FVC, where FVC was defined as the total volume of air that a participant can breathe out forcefully from a full breath, blowing all of it out. The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier. The mITT included all randomized participants who received at least 1 dose of study treatment analyzed according to the treatment group allocated by randomization. Only participants with data collected at specified times are reported. Here, n=number of participants with data collected for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Weeks 2, 4, 6, 8, 10, and 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The ACQ-5 is a questionnaire that measured the adequacy of asthma control and any changes in asthma control that occurred spontaneously or as a result of treatment. The ACQ-5 has 5 questions on the asthma symptoms experienced by participants during the past week and to respond on a 7-point scale for each question (0 = no impairment, 6 = maximum impairment). The ACQ-5 score is the mean of the 5 questions and total score ranged from 0 (totally controlled) to 6 (severely uncontrolled), a high score indicates low asthma control. The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier. The mITT population. Only n=number of participants with data collected at specified times for specified categories are reported.
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Weeks 2, 4, 6, 8, 10, and 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Self-Administered Score | |||||||||||||||||||||||||||||||||||
End point description |
The AQLQ (S) was a self-administered participant reported outcome (PRO) to measure the functional impairments in adult and adolescent participants. The instrument comprised of 32 items each rated on a 7-point Likert scales from 1 to 7. The AQLQ (S) has 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), and environmental stimuli (4 items). The score of each domain was the mean of response to each of the questions in that domain. The overall global score was calculated as the average of the 32 questions and ranges from 1 (total impairment) to 7 (no impairment). Higher scores indicate better quality of life. The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier. The mITT population. Only n=number of participants with data collected at specified times for specified categories are reported.
|
|||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Weeks 4, 8, and 12
|
|||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Asthma Daytime Symptom Diary (ADSD) Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
ADSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete ADSD every night before they go to bed, thinking about their asthma symptoms today, from when they got up this morning until now. ADSD is composed of 6 items rated using an 11-point numeric pain scale (NRS) that ranges from 0 = None to 10 = as bad as you can imagine. Total score was calculated by averaging all 6 items and the score ranged from 0 to 10. Higher scores indicated worse outcomes. The baseline is defined as available value on latest date up to randomization date or first double-blind study treatment date whichever occurs earlier. mITT population. Only n=number of participants with data collected at specified times for specified categories are reported.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Asthma Night Time Symptom Diary (ANSD) Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
ANSD is a PRO measure designed to measure asthma symptoms in adult and adolescent participants diagnosed with mild to severe asthma. ANSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e.,difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete ANSD when getting up, thinking about their asthma symptoms last night from when they went to bed until now. ANSD is composed of 6 items rated using an 11-point NRS that ranges from 0 (None) to 10 (as bad as you can imagine). Total score was calculated by averaging all 6 items and therefore the score ranged from 0 to 10. Higher scores indicated worse outcomes. The baseline is defined as available value on latest date up to randomization date or first double-blind study treatment date whichever occurs earlier. The mITT population. Only n=number of participants with data collected at specified times for specified categories are reported.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Plasma Concentrations of Rilzabrutinib Over Time [1] | ||||||||||||||||||||||||||||||||||||
End point description |
Plasma samples were obtained and analyzed at specified timepoints for pharmacokinetic (PK) characterization of rilzabrutinib. PK population included all randomized and treated participants with at least 1 post-baseline PK sample with adequate documentation of dosing and sampling dates and times. Only n=number of participants with data collected at specified times for specified categories are reported.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose Day 1, Weeks 2, 4, 8 and 12; 2 hour post-dose Day 1, Weeks 4, and 8
|
||||||||||||||||||||||||||||||||||||
Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only PK population included all randomized and treated participants treated with Rilzabrutinib with at least 1 post-baseline PK sample with adequate documentation of dosing and sampling dates and times. Only n=number of participants with data collected at specified times for specified categories are reported. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||
End point title |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | |||||||||||||||||||||||||
End point description |
Adverse event (AE): any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of study treatment (on Day 1) to last administration of study treatment + 7 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Safety population included all randomized participants who took at least 1 dose of study treatment.
|
|||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||
End point timeframe |
From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days, approximately 91 days
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Numbers of Inhalations/day of Albuterol or Levalbuterol for Symptom Relief | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of albuterol or levalbuterol inhalations were recorded daily by the participants in the electronic diary. A diary day is defined as the period beginning with an evening diary and ending with the following day’s morning Diary. A diary day was not included in the calculation if an evening or morning diary is missing. The reliever medication baseline value was the average number of puffs taken in the most recent 7 diary days before next visit. The baseline is defined as the available value on the latest date up to the randomization date or the first double-blind study treatment date whichever occurs earlier. The mITT included all randomized participants who received at least 1 dose of study treatment analyzed according to the treatment group allocated by randomization. Only n=number of participants with data collected at specified times for specified categories are reported.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events and all-cause mortality (death) were collected from first dose of study drug (Day 1) up to last dose of study treatment + 7 days, approximately 91 days.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Analysis was performed on safety population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo BID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants were administered placebo orally BID on Day 1 for 12 weeks, added to background therapy of ICS/LABA fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo TID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants were administered placebo orally TID on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rilzabrutinib 400mg TID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants were administered rilzabrutinib 400 mg orally TID on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rilzabrutinib 400mg BID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants were administered rilzabrutinib 400 mg orally BID on Day 1 for 12 weeks added to background therapy of ICS/LABA, fluticasone/salmeterol combination therapy at stable dose for 4 weeks. Salmeterol was withdrawn at Week 4; fluticasone was administered up to Week 9 and gradually withdrawn from Week 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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23 Feb 2022 |
This amendment was to evaluate the efficacy and safety of 2 different dose of regimens of rilzabrutinib, the current dose of 400 mg BID and an additional higher regimen of 400 mg TID in two staggered double-blind cohorts for a total number of 192 participants split. There were some editorial changes for better clarification and consistency. |
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13 Sep 2022 |
To update exclusion and inclusion criteria. Other minor clarifications and corrections deemed necessary by the Sponsor were also
implemented. |
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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 |