Clinical Trial Results:
A randomized, double-blind, placebo-controlled, 12-week treatment study to evaluate the effect of ACT-774312 in subjects with bilateral nasal polyposis
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Summary
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EudraCT number |
2018-000851-42 |
Trial protocol |
BE DE |
Global end of trial date |
01 Dec 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Nov 2021
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First version publication date |
27 Nov 2021
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Other versions |
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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 |
ID-084A201
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03688555 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Idorsia Pharmaceuticals Ltd
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Sponsor organisation address |
Hegenheimermattweg 91, Allschwil, Switzerland, 4123
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Public contact |
Clinical Trial Disclosure Desk, Idorsia Pharmaceuticals Ltd, +41 58 844 19 77, clinical-trials-disclosure@idorsia.com
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Scientific contact |
Clinical Trial Disclosure Desk, Idorsia Pharmaceuticals Ltd, +41 58 844 19 77, clinical-trials-disclosure@idorsia.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 |
04 Jan 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Dec 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Dec 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 |
To evaluate the effect of ACT-774312 on bilateral nasal polyposis (NP).
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Protection of trial subjects |
Prior to the start of the study, each study site consulted an Independent Ethics Committee (IEC), i.e., a review panel that was responsible for ensuring the protection of the rights, safety, and well-being of human subjects involved in a clinical investigation. The protocol and any material provided to the subject (such as a subject information sheet or description of the study used to obtain informed consent) were reviewed and approved by the appropriate IEC before the study was started. Sponsor personnel and the investigators were required to conduct the study in full compliance with ICH GCP Guidelines, the principles of the Declaration of Helsinki, and with the laws and regulations of the countries in which the study is conducted. Both the sponsor and the investigators had the right to terminate the study at any time, and in such a case, were responsible for protecting the subjects’ interests. The investigators were responsible for maintaining the subjects’ identities in strictest confidence. Written informed consent was required to be obtained from each individual participating in the study prior to any study procedure and after adequate explanation of the aims, methods, objectives, and potential hazards of the study. It was made clear to each subject that he or she was completely free to refuse to enter the study, or to withdraw from it at any time for any reason.
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Background therapy |
Mandatory medications: - Non-investigational medicinal product (standard background therapy): Mometasone furoate nasal spray 50 μg/actuation nasal spray, suspension. Dosing regimen: 2 actuations (50 μg/actuation) in each nostril twice daily (or once daily if twice daily was not tolerated). - Mandatory therapy included any treatments required for contraception purposes in women of childbearing potential. All subjects with asthma continued their prescribed treatment throughout the study. Additionally, 4 subjects took study-concomitant medications to treat other ongoing co-morbidities (hypercholesterolemia, gastritis, hypertension, and allergy). Other study-concomitant medications were administered to treat acute infections or infestations. These concomitant medications were not expected to interact with ACT-774312. | ||
Evidence for comparator |
In this study, ACT-774312 was compared to placebo. Both study treatments were administered on top of standard background therapy: mometasone furoate nasal spray therapy. | ||
Actual start date of recruitment |
19 Oct 2018
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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 |
Belgium: 3
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Country: Number of subjects enrolled |
Germany: 7
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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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) |
9
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted between the 19 Oct 2018 and 01 Dec 2020. The study was conducted at 2 sites in 2 countries (Belgium and Germany), both sites randomized subjects. | |||||||||||||||
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Pre-assignment
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Screening details |
The screening period lasted for up to 21 days. This period started with the screening visit (Visit 1) and ended on Day 1 (Visit 2) just before the first ACT-774312 or placebo administration. At screening, subjects were on a stable regimen of intranasal corticosteroids for at least 8 weeks. | |||||||||||||||
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Period 1
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Period 1 title |
Treatment period (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, Data analyst, Carer, Assessor | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ACT-774312 | |||||||||||||||
Arm description |
ACT-774312 was administered twice daily for 12 weeks | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
ACT-774312
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received ACT-774312 400 mg twice daily in the morning and evening with or without food for 12 weeks.
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Arm title
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Placebo | |||||||||||||||
Arm description |
Matching placebo capsules were administered twice daily for 12 weeks | |||||||||||||||
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 |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received matching placebo capsules in the morning and evening with or without food for 12 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
ACT-774312
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Reporting group description |
ACT-774312 was administered twice daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Matching placebo capsules were administered twice daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
ACT-774312
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The ACT-774312 per protocol set included all randomized subjects that completed the ACT-774312 treatment up to Week 12 without protocol deviations that could affect the evaluation of the primary endpoint.
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Subject analysis set title |
Matching Placebo
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The matching placebo per protocol set included all randomized subjects that completed the ACT-774312 treatment up to Week 12 without protocol deviations that could affect the evaluation of the primary endpoint.
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End points reporting groups
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Reporting group title |
ACT-774312
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Reporting group description |
ACT-774312 was administered twice daily for 12 weeks | ||
Reporting group title |
Placebo
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Reporting group description |
Matching placebo capsules were administered twice daily for 12 weeks | ||
Subject analysis set title |
ACT-774312
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The ACT-774312 per protocol set included all randomized subjects that completed the ACT-774312 treatment up to Week 12 without protocol deviations that could affect the evaluation of the primary endpoint.
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Subject analysis set title |
Matching Placebo
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The matching placebo per protocol set included all randomized subjects that completed the ACT-774312 treatment up to Week 12 without protocol deviations that could affect the evaluation of the primary endpoint.
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End point title |
Change from Baseline to Week 12 in the Nasal Polyps Score | ||||||||||||
End point description |
Independent reviewers, blinded to treatment, reviewed image recordings of nasal endoscopies to determine total endoscopic nasal polyp score (NPS) based on nasal polyp (NP) size. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction/congestion of the inferior meatus). The total score is the sum of the right and left nostril scores and ranges from 0 to 8, higher scores indicate greater disease severity. Data up to Week 12 were included in the analyses. The main analysis was performed on the per-protocol set. Baseline was defined as Day 1 value. Change from Baseline = (Post-baseline visit value) minus (Baseline visit value).
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End point type |
Primary
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End point timeframe |
Baseline (Day 1) and Week 12.
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Statistical analysis title |
ACT-774312 vs placebo | ||||||||||||
Statistical analysis description |
All Nasal Polyp Score (NPS) values observed between baseline and Week 12 were included in the analysis. Changes from baseline to post-baseline visits in NPS were analyzed using a Mixed Model for Repeated Measurement (MMRM).
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Comparison groups |
ACT-774312 v Matching Placebo
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Number of subjects included in analysis |
7
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.062 | ||||||||||||
Method |
Mixed model for repeated measurements | ||||||||||||
Parameter type |
LS means difference | ||||||||||||
Point estimate |
0.76
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.06 | ||||||||||||
upper limit |
1.59 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.301
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End point title |
Change from Baseline to Week 12 in the sinus opacifications as assessed by Computer Tomography Scan using the modified Lund-Mackay Score | ||||||||||||
End point description |
Independent blinded reviewers reviewed image recordings of the computed tomography scan. The modified Lund Mackay Score scores were given for the degree of opacification and their location in the sinus. The right and left sinuses are divided into 6 portions, i.e., maxillary sinus, anterior ethmoid sinuses, posterior ethmoid sinuses, sphenoid sinus, frontal sinus, and ostiomeatal complex (OMC). The OMC is given a score of 0 (no obstruction) or 1 (obstruction) for the frontal recess, middle meatus, infundibulum, and the sphenoethmoidal recess channels. The total score is the sum of the right and left nostril scores and range from 0 to a maximum of 48. A positive change from baseline (Day 1) indicates a worsening.
Change in the modified Lund-Mackay score = (modified Lund-Mackay score at Week 12) minus (modified Lund-Mackay score at baseline).
A positive change from baseline indicated a worsening in the modified Lund-Mackay Score at Week 12 compared to baseline.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline) and Week 12.
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Statistical analysis title |
Per-protocol analysis set: ACT-774312 vs placebo | ||||||||||||
Statistical analysis description |
The change from baseline to Week 12 in modified Lund-Mackay score was analyzed on the per protocol population using an ANCOVA model with a factor for treatment group and a covariate for the baseline score.
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Comparison groups |
ACT-774312 v Matching Placebo
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Number of subjects included in analysis |
7
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.161 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
LS means difference | ||||||||||||
Point estimate |
-3.98
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-10.41 | ||||||||||||
upper limit |
2.45 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
2.316
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End point title |
Change from Baseline to Week 12 in the Volume of Air in the Left Maxillary Sinus | ||||||||||||
End point description |
Independent reviewers, blinded to treatment, reviewed image recordings of the computed tomography scan and performed 3D volumetric measurements of the left maxillary sinus. Absolute changes from baseline were calculated for volume of air (mL). Change in 3D volumetric measurement = (3D volumetric measurement at Week 12) minus (3D volumetric measurement at baseline). A positive change from baseline indicates that more volume for air is in the left maxillary sinus since the baseline visit. More volume of air indicates that the polyposis is improving in the left maxillary sinus.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline) and Week 12
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End point title |
Change from Baseline to Week 12 in the Volume of Air in the Right Maxillary Sinus | ||||||||||||
End point description |
Independent reviewers, blinded to treatment, reviewed image recordings of the computed tomography scan and performed 3D volumetric measurements of the right maxillary sinus.
Absolute changes from baseline were calculated for the volume of air (mL) in the right maxillary sinus: Change in 3D volumetric measurement = (3D volumetric measurement at Week 12) minus (3D volumetric measurement at baseline). A positive change from baseline indicates that more volume for air is in the right maxillary sinus since the baseline visit. More volume of air indicates that the polyposis is improving in the right maxillary sinus.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline) and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline to Week 12 in the Left Maxillary Sinus Mucosal Volume | ||||||||||||
End point description |
Independent reviewers, blinded to treatment, reviewed image recordings of the computed tomography scan and performed 3D volumetric measurements of the left maxillary sinus.
Absolute changes from baseline were calculated for the volume of air (mL) in the left maxillary sinus: Change in 3D volumetric measurement = (3D volumetric measurement at Week 12) minus (3D volumetric measurement at baseline). A negative change from baseline indicates that the left maxillary sinus mucosal volume has decreased since the baseline visit. More mucosal volume, a positive change, indicates that the polyposis is worsening in the left maxillary sinus.
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End point type |
Secondary
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End point timeframe |
Day 1 (baseline) and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline to Week 12 in the Right Maxillary Sinus Mucosal Volume | ||||||||||||
End point description |
Independent reviewers, blinded to treatment, reviewed image recordings of the computed tomography scan and performed 3D volumetric measurements of the right maxillary sinus.
Absolute changes from baseline were calculated for the volume of air (mL) in the right maxillary sinus: Change in 3D volumetric measurement = (3D volumetric measurement at Week 12) minus (3D volumetric measurement at baseline). A negative change from baseline indicates that the right maxillary sinus mucosal volume has decreased since the baseline visit. More mucosal volume, a positive change, indicates that the polyposis is worsening in the right maxillary sinus.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline) and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline to Week 12 in the University of Pennsylvania Smell Identification Test | ||||||||||||
End point description |
The UPSIT (University of Pennsylvania Smell Identification Test) is a test that measures an individual's ability to detect odors. It consists of 4 workbooks of 10 pages each. On each page there is a different
"scratch and sniff" strip which is embedded with a micro-encapsulated odorant and a question regarding the smell detected with a four-choice option for the response. The total number of questions in the UPSIT is 40. The number of correct responses regarding the smells being experienced is summed to provide a total score that ranges from 0 to 40, with a higher score indicating a better sense of smell.
Absolute changes from baseline to Week 12 was calculated as follows: Change in UPSIT score = (UPSIT score at Week 12) minus (UPSIT score at baseline). A positive change from baseline in the UPSIT score is considered a favorable outcome.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline) and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in the Visual Analog Scale Symptoms Score | |||||||||||||||||||||||||||
End point description |
The subject was asked to score on a Visual Analog Scale (VAS) the answer to the question: “How troublesome are your symptoms?” (for the 5 following symptoms: nasal obstruction, nasal discharge, - mucus in the throat, loss of smell, facial pain). The VAS ranges from 0 (Not at all troublesome) to 100 (Extremely troublesome). The sum of the score of all symptoms were added to a total VAS score which ranged from 0 to 500. The higher the VAS score the more troublesome the symptoms. Absolute changes from baseline to Weeks 2, 4, 8, 12, and EOS are calculated as follows: Change in total VAS score = (Total VAS score at visit) minus (Total VAS score at baseline). A negative change from baseline indicates an improvement.
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End point type |
Secondary
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End point timeframe |
Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 and End of Study (Week 16)
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Physician Global Assessment of Change in Disease Severity | |||||||||||||||||||||||||||
End point description |
The Physician Global Assessment of Disease Severity questionnaire (PGAC-DS) was completed by the physician at Visit 2 and at each subsequent site visit until the End-of-Study (Week 16). The PGAC-DS questionnaire is a self-administered 1-item questionnaire designed to assess the physician’s impression of change in disease severity since study treatment start. The physician rated the change since the participant study treatment start. The physician rated the change since the participant started study treatment on a 7-point scale. The rating for the overall score is: ‘very much improved’ ( is scored 1), ‘much improved’ (is scored 2), ‘minimally improved’ (is scored 3), ‘no change’ (is scored 4), ‘minimally worse’ (is scored 5), ‘much worse’ (is scored 6), or ‘very much worse’ (is scored 7).
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End point type |
Secondary
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End point timeframe |
Week 2, Week 4, Week 8, Week 12, and End of Study (Week 16)
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Change from Baseline in the Sino-Nasal Outcome Test | |||||||||||||||||||||||||||
End point description |
SNOT-22 (Sino-Nasal Outcome Test) is a disease specific quality of life questionnaire measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every
subject was asked to rate how severe each problem had been for them over the past 2 weeks on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores
for all 22 items, ranging from 0 to 110. Higher total scores on the SNOT-22 imply greater impact on Quality of Life. Absolute changes from baseline to Weeks 2, 4, 8, 12, and 16 were calculated as follows: Change in SNOT-22 score = (SNOT-22 score at visit) minus (SNOT-22 score at baseline).
A negative change from baseline in SNOT-22 is considered a favorable outcome.
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End point type |
Secondary
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End point timeframe |
Week 2, Week 4, Week 8, Week 12, End of Study (Week 16)
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Patient Global Impression of Change in Disease Severity | |||||||||||||||||||||||||||
End point description |
A patient global impression of change in disease severity questionnaire (PGIC-DS) was completed by the subject at Week 2 and at each subsequent site visit until the End of study visit.
The PGIC-DS questionnaire was a self-administered 1-item questionnaire designed to assess subject’s impression of change in disease severity since study treatment start.
Subjects rated their change since they started study treatment for the overall severity of the disease symptoms on a 7-point scale (1 to 7) scored as: “very much improved (1),” “much improved,” (2)
“minimally improved,”(3) “no change,” (4) “minimally worse,” (5) “much worse,” (6) or “very much worse” (7).
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End point type |
Secondary
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End point timeframe |
Week 2, Week 4, Week 8, Week 12, End of Study (Week 16)
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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 |
Treatment-emergent adverse events were all adverse events that occurred after first study treatment administration on Day 1 through to last study treatment administration on Day 84, and in the post-treatment period up to the end-of-study visit on Day 112.
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Adverse event reporting additional description |
A treatment-emergent adverse event is any adverse event temporally associated with the use of a study treatment, whether or not considered related to the study treatment in all subjects that took at least one dose of treatment (placebo or ACT-774312).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |
ACT-774312
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Reporting group description |
ACT-774312 was administered twice daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Matching placebo capsules were administered twice daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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15 Aug 2019 |
The study was initially planned as a single-center study. Due to difficulties in recruiting subjects, it was decided to open up 1 additional site outside of Belgium, that is in Germany. The title as well as the overall study design and plan and the analysis method of the primary endpoint were updated accordingly for approvals in Germany.
Eligibility criteria were changed:
- A body mass index greater than or equal to 18 kg/m2 was added as an inclusion criterion.
- Subject considered as vulnerable (e.g., sponsor or site employee, investigator subordinate, subject incapable of giving consent, subject committed to an institution by way of official or judicial order).
- To be included the systolic blood pressure 90−160 mmHg, diastolic blood pressure 50−100 mmHg, and pulse rate 45−100 bpm (inclusive), measured on the dominant arm, after 5 minutes in the supine position at screening.
- Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test pre-dose on Day 1.
The assessment of the CT scans with the Lund-Mackay methodology was added.
Study-specific criteria for interruption / premature discontinuation of study treatment was added:
- The stopping criteria at the study level on thrombopenia was added.
- A subject had to be immediately and permanently discontinued from study treatment if either of the following occurred:
- severe thrombopenia (platelet count less than 50,000/μL) while on investigational treatment.
- systolic blood pressure < 80 mmHg and diastolic blood pressure < 60 mmHg (confirmed by repeated BP measurement within 10 min) and associated with significant clinical symptoms while on investigational treatment.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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. | |||||||
| The p-values need to be cautiously interpreted due to the small study population size. | |||||||
