Trial Outcomes & Findings for A Study to Evaluate the Effect of ACT-774312 in Subjects With Bilateral Nasal Polyposis (NCT NCT03688555)
NCT ID: NCT03688555
Last Updated: 2022-04-11
Results Overview
Independent reviewers, blinded to treatment, reviewed image recordings of nasal endoscopies to determine total endoscopic nasal polyp score based on nasal polyp 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 Day 1 value was the baseline. Change from Baseline = (Post-baseline visit value) minus (Baseline visit value). A negative change indicates worsening.
COMPLETED
PHASE2
10 participants
Pre-dose (Baseline on Day 1) and Week 12
2022-04-11
Participant Flow
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 participants.
At screening, patients were on a stable regimen of intranasal corticosteroids (INCS) for at least 8 weeks. If a participant was using an INCS product different from mometasone furoate nasal spray prior to the screening visit, the investigator had to switch to mometasone furoate nasal spray at screening (Visit 1). Only once a participant was eligible for randomization was data collected.
Participant milestones
| Measure |
Mometasone Furoate
All participants were placed on non-investigational, standard background therapy: Mometasone furoate nasal spray 50 μg/actuation nasal spray, suspension for 4 weeks (Visit 1 to Visit 2). Dosing regimen: 2 actuations (50 μg/actuation) in each nostril twice daily (or once daily if twice daily was not tolerated).
|
ACT-774312
Participants received ACT-774312 400 mg twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|---|
|
Run-in Period
STARTED
|
10
|
0
|
0
|
|
Run-in Period
COMPLETED
|
10
|
0
|
0
|
|
Run-in Period
NOT COMPLETED
|
0
|
0
|
0
|
|
Treatment Period
STARTED
|
0
|
7
|
3
|
|
Treatment Period
COMPLETED
|
0
|
7
|
2
|
|
Treatment Period
NOT COMPLETED
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Mometasone Furoate
All participants were placed on non-investigational, standard background therapy: Mometasone furoate nasal spray 50 μg/actuation nasal spray, suspension for 4 weeks (Visit 1 to Visit 2). Dosing regimen: 2 actuations (50 μg/actuation) in each nostril twice daily (or once daily if twice daily was not tolerated).
|
ACT-774312
Participants received ACT-774312 400 mg twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|---|
|
Treatment Period
Adverse Event
|
0
|
0
|
1
|
Baseline Characteristics
A Study to Evaluate the Effect of ACT-774312 in Subjects With Bilateral Nasal Polyposis
Baseline characteristics by cohort
| Measure |
ACT-774312
n=7 Participants
Participants received ACT-774312 400 mg twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=3 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
50.3 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
54.7 years
STANDARD_DEVIATION 5.5 • n=7 Participants
|
51.6 years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
5 participants
n=5 Participants
|
2 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
28.2 kilogram(s)/square meter
STANDARD_DEVIATION 5.25 • n=5 Participants
|
26.0 kilogram(s)/square meter
STANDARD_DEVIATION 2.81 • n=7 Participants
|
27.5 kilogram(s)/square meter
STANDARD_DEVIATION 4.61 • n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (Baseline on Day 1) and Week 12Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
Independent reviewers, blinded to treatment, reviewed image recordings of nasal endoscopies to determine total endoscopic nasal polyp score based on nasal polyp 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 Day 1 value was the baseline. Change from Baseline = (Post-baseline visit value) minus (Baseline visit value). A negative change indicates worsening.
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Change From Baseline to Week 12 in Nasal Polyp Score as Measured by Nasal Endoscopy (Assessed Centrally)
|
-0.23 score on a scale
Standard Error 0.161
|
-0.99 score on a scale
Standard Error 0.253
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline on Day 1) and Week 12Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
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 the 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.
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Change From Baseline to Week 12 in Sinus Opacifications as Assessed by Computed Tomography Scan Using the Modified Lund Mackay Score (Assessed Centrally)
|
0.86 score on a scale
Standard Error 1.24
|
4.84 score on a scale
Standard Error 1.96
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline on Day 1) and Week 12Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
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.
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Change From Baseline to Week 12 in the Volume of Air in the Left Maxillary Sinus
|
1.17 milliliter(s)
Standard Deviation 1.72
|
-1.08 milliliter(s)
Standard Deviation 2.48
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline on Day 1) and Week 12Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
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.
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Change From Baseline to Week 12 in the Volume of Air in the Right Maxillary Sinus
|
-0.94 milliliter(s)
Standard Deviation 4.36
|
1.77 milliliter(s)
Standard Deviation 1.34
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline on Day 1) and Week 12Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
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.
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Change From Baseline to Week 12 in the Left Maxillary Sinus Mucosal Volume
|
-1.72 milliliter(s)
Standard Deviation 1.72
|
-1.08 milliliter(s)
Standard Deviation 2.48
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline on Day 1) and Week 12Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
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.
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Change From Baseline to Week 12 in the Right Maxillary Sinus Mucosal Volume
|
0.94 milliliter(s)
Standard Deviation 4.36
|
-1.78 milliliter(s)
Standard Deviation 1.34
|
SECONDARY outcome
Timeframe: Pre-dose (Baseline on Day 1) and Week 12Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
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.
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Change From Baseline to Week 12 in the University of Pennsylvania Smell Identification Test
|
1.0 score on a scale
Standard Deviation 8.4
|
-0.5 score on a scale
Standard Deviation 0.7
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12 and Week 16 (End-of-Study)Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
The participant 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 End of Study are calculated as follows: Change in total VAS score = Change in total VAS score = (Total VAS score at visit) minus (Total VAS score at baseline). A negative change from baseline indicates an improvement.. A negative change from baseline indicates an improvement.
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Change From Baseline in the Visual Analog Scale Symptoms Score
Baseline
|
304.0 score on a scale
Standard Deviation 75.0
|
323.5 score on a scale
Standard Deviation 95.5
|
|
Change From Baseline in the Visual Analog Scale Symptoms Score
Change from baseline at Week 2
|
-69.8 score on a scale
Standard Deviation 68.4
|
-77.5 score on a scale
Standard Deviation 136.5
|
|
Change From Baseline in the Visual Analog Scale Symptoms Score
Change from baseline at Week 4
|
-108.0 score on a scale
Standard Deviation 106.0
|
-58.0 score on a scale
Standard Deviation 18.4
|
|
Change From Baseline in the Visual Analog Scale Symptoms Score
Change from baseline at Week 8
|
-70.5 score on a scale
Standard Deviation 121.3
|
-88.5 score on a scale
Standard Deviation 61.5
|
|
Change From Baseline in the Visual Analog Scale Symptoms Score
Change from baseline at Week 12
|
-90.0 score on a scale
Standard Deviation 55.9
|
-156.0 score on a scale
Standard Deviation 123.7
|
|
Change From Baseline in the Visual Analog Scale Symptoms Score
Change from baseline at Week 16 (End-of-Study)
|
-105.4 score on a scale
Standard Deviation 78.9
|
-57.0 score on a scale
Standard Deviation 104.7
|
SECONDARY outcome
Timeframe: Week 2, Week 4, Week 8, Week 12, and Week 16 (End-of-Study)Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
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).
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Physician Global Assessment of Change in Disease Severity
Week 2
|
3.4 score on a scale
Standard Deviation 0.5
|
3.0 score on a scale
Standard Deviation 1.4
|
|
Physician Global Assessment of Change in Disease Severity
Week 4
|
3.0 score on a scale
Standard Deviation 0.7
|
3.0 score on a scale
Standard Deviation 1.4
|
|
Physician Global Assessment of Change in Disease Severity
Week 8
|
3.6 score on a scale
Standard Deviation 1.3
|
2.5 score on a scale
Standard Deviation 0.7
|
|
Physician Global Assessment of Change in Disease Severity
Week 12
|
3.4 score on a scale
Standard Deviation 0.5
|
4.0 score on a scale
Standard Deviation 1.4
|
|
Physician Global Assessment of Change in Disease Severity
Week 16 (End-of-Study)
|
3.6 score on a scale
Standard Deviation 0.5
|
4.0 score on a scale
Standard Deviation 1.4
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12, and Week 16 (End-of-Study)Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
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 participant 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.
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Change From Baseline in the Sino-Nasal Outcome Test
Baseline
|
61.4 score on a scale
Standard Deviation 9.2
|
59.5 score on a scale
Standard Deviation 19.1
|
|
Change From Baseline in the Sino-Nasal Outcome Test
Change from baseline at Week 2
|
-7.2 score on a scale
Standard Deviation 18.5
|
-22.5 score on a scale
Standard Deviation 27.6
|
|
Change From Baseline in the Sino-Nasal Outcome Test
Change from baseline at Week 4
|
-21.4 score on a scale
Standard Deviation 11.0
|
-21.5 score on a scale
Standard Deviation 16.3
|
|
Change From Baseline in the Sino-Nasal Outcome Test
Change from baseline at Week 8
|
-14.4 score on a scale
Standard Deviation 14.7
|
-29.0 score on a scale
Standard Deviation 18.4
|
|
Change From Baseline in the Sino-Nasal Outcome Test
Change from baseline at Week 12
|
-15.2 score on a scale
Standard Deviation 5.3
|
-21.5 score on a scale
Standard Deviation 16.3
|
|
Change From Baseline in the Sino-Nasal Outcome Test
Change from baseline at Week 16 (End-of-Study)
|
-16.4 score on a scale
Standard Deviation 3.9
|
-24.0 score on a scale
Standard Deviation 22.6
|
SECONDARY outcome
Timeframe: Week 2, Week 4, Week 8, Week 12, and Week 16 (End-of-Study)Population: Per-protocol set. This analysis set includes all randomized participants who completed the treatment up to Week 12 without protocol deviations that may affect the evaluation of the primary endpoints.
A patient global impression of change in disease severity questionnaire (PGIC-DS) was completed by the participant 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 participant's impression of change in disease severity since study treatment start. Participants 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).
Outcome measures
| Measure |
ACT-774312
n=5 Participants
Participants received ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=2 Participants
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Patient Global Impression of Change in Disease Severity
Week 2
|
3.2 score on a scale
Standard Deviation 0.4
|
2.5 score on a scale
Standard Deviation 2.1
|
|
Patient Global Impression of Change in Disease Severity
Week 4
|
3.0 score on a scale
Standard Deviation 0.7
|
2.5 score on a scale
Standard Deviation 2.1
|
|
Patient Global Impression of Change in Disease Severity
Week 8
|
3.4 score on a scale
Standard Deviation 1.5
|
2.0 score on a scale
Standard Deviation 0.0
|
|
Patient Global Impression of Change in Disease Severity
Week 12
|
3.4 score on a scale
Standard Deviation 0.5
|
2.0 score on a scale
Standard Deviation 0.0
|
|
Patient Global Impression of Change in Disease Severity
Week 16 (End-of-Study)
|
3.4 score on a scale
Standard Deviation 0.9
|
2.5 score on a scale
Standard Deviation 0.7
|
Adverse Events
ACT-774312
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
ACT-774312
n=7 participants at risk
Participants received ACT-774312 400 mg twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
Placebo
n=3 participants at risk
Participants received matching placebo hard gelatin capsules twice daily in the morning and evening with or without food for 12 weeks. In addition, participants also continued with their standard background therapy of mometasone furoate nasal spray.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
14.3%
1/7 • Number of events 1 • 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.
|
33.3%
1/3 • Number of events 2 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic rhinosinusitis with nasal polyps
|
14.3%
1/7 • Number of events 1 • 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.
|
0.00%
0/3 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal inflammation
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Nervous system disorders
Headache
|
14.3%
1/7 • Number of events 1 • 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.
|
0.00%
0/3 • 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.
|
|
General disorders
Fatigue
|
14.3%
1/7 • Number of events 1 • 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.
|
33.3%
1/3 • Number of events 2 • 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.
|
|
Gastrointestinal disorders
Dyspepsia
|
14.3%
1/7 • Number of events 1 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Reproductive system and breast disorders
Premenstrual headache
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.3%
1/7 • Number of events 1 • 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.
|
0.00%
0/3 • 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.
|
|
Infections and infestations
Nasopharyngitis
|
14.3%
1/7 • Number of events 1 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Infections and infestations
Rhinitis
|
14.3%
1/7 • Number of events 1 • 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.
|
0.00%
0/3 • 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.
|
|
Infections and infestations
Influenza
|
14.3%
1/7 • Number of events 1 • 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.
|
0.00%
0/3 • 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.
|
|
Infections and infestations
Vulvovaginal candidiasis
|
14.3%
1/7 • Number of events 1 • 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.
|
0.00%
0/3 • 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.
|
|
Infections and infestations
Myringitis
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
|
Infections and infestations
Otosalpingitis
|
0.00%
0/7 • 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.
|
33.3%
1/3 • Number of events 1 • 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.
|
Additional Information
Clinical Trials Disclosure Desk
Idorsia Pharmaceuticals Ltd
Results disclosure agreements
- Principal investigator is a sponsor employee Any study-related publication written independently by investigators must be submitted to Idorsia for review at least 30 days prior to submission for publication or presentation. Upon review, Idorsia may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights. Neither the institution nor the investigator should permit publication during such a review period.
- Publication restrictions are in place
Restriction type: OTHER