Bilateral Nasal Polyposis
Conditions
Brief summary
The study will evaluate the effect of ACT-774312 on the nasal polyps and will assess the safety and tolerability of ACT-774312 in the patients with bilateral nasal polyposis
Detailed description
The clinical trial has 3 periods: Screening and run-in period (4 Weeks). This period starts with the screening visit, and ends on Day 1, just before the first study treatment administration. At Visit 1, all participants will enter a run-in period of 4 weeks on mometasone furoate nasal spray of 2 actuations (50 μg per actuation) in each nostril twice daily (total daily dose of 400 μg), unless they were intolerant to twice daily intranasal corticosteroids, in which case they could use a lower dose regimen, i.e., 200 μg once daily. Treatment period (ACT-774312 or placebo for 12 weeks). This period will start on Day 1 with the first administration of study treatment and consists of 4 visits: Week 2, Week 4, Week 8, and Week 12. Provided that the nasal polyp score (NPS) does not change during the run-in period, participants will be randomized to ACT-774312 (400 mg twice daily) or placebo (twice daily) for 12 weeks. During the double-blind randomized treatment all participants will continue with mometasone furoate nasal spray background therapy. Post-treatment period (4 Weeks). This period will start after the Week 12 Visit and end at Week 16 (End-of-Study).
Interventions
DRUGACT-774312
ACT-774312 will be available as hard gelatin capsules containing 200 mg of ACT-774312
DRUGPlacebo
Matching placebo hard gelatin capsules
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent in the local language prior to any study mandated procedure. * A minimum bilateral nasal polyp score (NPS) of 5 out of a maximum of 8 for both nostrils (with at least a score of 2 for each nostril) despite completion of a prior intranasal corticosteroids (INCS) treatment for at least 8 weeks before screening, with at least the 6 last weeks on INCS spray. * Presence of at least 2 of the following symptoms at screening: * nasal blockade/obstruction * nasal discharge (anterior/posterior nasal drip) * reduction or loss of smell. * Male and female participants aged between 18 and 70 years (inclusive) at screening. * Systolic blood pressure 90 to 160 mmHg, diastolic blood pressure 50 to 100 mmHg, pulse rate 45 to 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. Women of childbearing potential must consistently and correctly use (from at least first dosing, during the entire study, and for at least 30 days after last study treatment intake) 1 highly effective method of contraception with a failure rate of less than 1% per year, be sexually abstinent, or have a vasectomized partner. Hormonal contraceptive must have been initiated at least 1 month before first study treatment administration.
Exclusion criteria
* CYP2C9 poor metabolizer. * Participant with severe renal function impairment (≤ 29 mL/min/1.73 m2) which is defined by estimated glomerular filtration rate at screening using the Modification of Diet in Renal Disease (MDRD) formula. * Participant with Sino-Nasal Outcome Test (SNOT-22) less than 20. * Participant who has required oral corticosteroids (OCS) within the 2 months before screening or is scheduled to receive OCS during the study period for another condition. * Participant who has required INCS drops within the 6 weeks before screening. * Participant who was injected with long-lasting activity corticosteroids within the 3 months before screening or is scheduled to receive these during the study period for another condition. * Participant who has undergone any nasal surgery within 6 months before screening. * Participant with conditions/concomitant diseases making them non-evaluable for the primary efficacy endpoint such as: * Antrochoanal polyps * Nasal septal deviation that occludes at least one nostril * Acute sinusitis, nasal infection or upper respiratory infection at screening or in the 2 weeks before screening * Ongoing rhinitis medicamentosa * Churg-Strauss syndrome, Young's syndrome, Kartagener's syndrome or dyskinetic ciliary syndromes, Cystic fibrosis * Signs or a CT scan suggestive of Allergic fungal rhinosinusitis. * Participants with co-morbid asthma are excluded if: * Forced expiratory volume in one second (FEV1) ≤ 60% of predicted normal OR * An exacerbation requiring systemic (oral and/or parenteral) steroid treatment or hospitalization (\>24 h) for treatment of asthma has occurred within 3 months prior screening OR * They are on a dose higher than 1000 μg fluticasone or the equivalent of inhaled corticosteroids (ICS). * Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. * Participants with active autoimmune disease (e.g., Hashimoto's thyroiditis, Graves' disease, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, psoriasis vulgaris, rheumatoid arthritis). * Participant considered as vulnerable (e.g., sponsor or site employee, investigator subordinate, participant incapable of giving consent, participant committed to an institution by way of official or judicial order). * Participant with liver injury related criteria: * Underlying hepatobiliary disease OR * Alanine aminotransferase greater than 3 x upper limit of normal, OR * or Bilirubin greater than 2 x upper limit of normal. * Participant with unstable NPS during the run-in period, i.e. altered score at Day 1 when compared to the screening NPS (assessed locally by the investigator).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Nasal Polyp Score as Measured by Nasal Endoscopy (Assessed Centrally) | Pre-dose (Baseline on Day 1) and Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in the Volume of Air in the Left Maxillary Sinus | Pre-dose (Baseline on Day 1) and Week 12 | 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. |
| Change From Baseline to Week 12 in the Volume of Air in the Right Maxillary Sinus | Pre-dose (Baseline on Day 1) and Week 12 | 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. |
| Change From Baseline to Week 12 in the Left Maxillary Sinus Mucosal Volume | Pre-dose (Baseline on Day 1) and Week 12 | 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. |
| Change From Baseline to Week 12 in the Right Maxillary Sinus Mucosal Volume | Pre-dose (Baseline on Day 1) and Week 12 | 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. |
| Change From Baseline to Week 12 in Sinus Opacifications as Assessed by Computed Tomography Scan Using the Modified Lund Mackay Score (Assessed Centrally) | Pre-dose (Baseline on Day 1) and Week 12 | 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. |
| Change From Baseline in the Visual Analog Scale Symptoms Score | Baseline, Week 2, Week 4, Week 8, Week 12 and Week 16 (End-of-Study) | 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. |
| Physician Global Assessment of Change in Disease Severity | Week 2, Week 4, Week 8, Week 12, and Week 16 (End-of-Study) | 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). |
| Change From Baseline in the Sino-Nasal Outcome Test | Baseline, Week 2, Week 4, Week 8, Week 12, and Week 16 (End-of-Study) | 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. |
| Patient Global Impression of Change in Disease Severity | Week 2, Week 4, Week 8, Week 12, and Week 16 (End-of-Study) | 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). |
| Change From Baseline to Week 12 in the University of Pennsylvania Smell Identification Test | Pre-dose (Baseline on Day 1) and Week 12 | 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. |
Countries
Belgium, Germany
Participant flow
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 participants.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| 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. | 3 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment Period | Adverse Event | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | ACT-774312 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 3 Participants | 9 Participants |
| Age, Continuous | 50.3 years STANDARD_DEVIATION 10.9 | 54.7 years STANDARD_DEVIATION 5.5 | 51.6 years STANDARD_DEVIATION 9.5 |
| Body Mass Index (BMI) | 28.2 kilogram(s)/square meter STANDARD_DEVIATION 5.25 | 26.0 kilogram(s)/square meter STANDARD_DEVIATION 2.81 | 27.5 kilogram(s)/square meter STANDARD_DEVIATION 4.61 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 9 Participants |
| Region of Enrollment Belgium | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Germany | 5 participants | 2 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 3 |
| other Total, other adverse events | 5 / 7 | 3 / 3 |
| serious Total, serious adverse events | 0 / 7 | 0 / 3 |
Outcome results
Primary
Change From Baseline to Week 12 in Nasal Polyp Score as Measured by Nasal Endoscopy (Assessed Centrally)
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.
Time frame: Pre-dose (Baseline on Day 1) and Week 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ACT-774312 | 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 |
| Placebo | Change From Baseline to Week 12 in Nasal Polyp Score as Measured by Nasal Endoscopy (Assessed Centrally) | -0.99 score on a scale | Standard Error 0.253 |
p-value: =0.06295% CI: [-0.06, 1.59]Mixed model for repeated measurements
Secondary
Change From Baseline in the Sino-Nasal Outcome Test
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACT-774312 | Change From Baseline in the Sino-Nasal Outcome Test | Baseline | 61.4 score on a scale | Standard Deviation 9.2 |
| ACT-774312 | 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 |
| ACT-774312 | Change From Baseline in the Sino-Nasal Outcome Test | Change from baseline at Week 4 | -21.4 score on a scale | Standard Deviation 11 |
| ACT-774312 | 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 |
| ACT-774312 | 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 |
| ACT-774312 | 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 |
| Placebo | Change From Baseline in the Sino-Nasal Outcome Test | Change from baseline at Week 12 | -21.5 score on a scale | Standard Deviation 16.3 |
| Placebo | Change From Baseline in the Sino-Nasal Outcome Test | Baseline | 59.5 score on a scale | Standard Deviation 19.1 |
| Placebo | Change From Baseline in the Sino-Nasal Outcome Test | Change from baseline at Week 8 | -29.0 score on a scale | Standard Deviation 18.4 |
| Placebo | Change From Baseline in the Sino-Nasal Outcome Test | Change from baseline at Week 2 | -22.5 score on a scale | Standard Deviation 27.6 |
| Placebo | Change From Baseline in the Sino-Nasal Outcome Test | Change from baseline at Week 16 (End-of-Study) | -24.0 score on a scale | Standard Deviation 22.6 |
| Placebo | Change From Baseline in the Sino-Nasal Outcome Test | Change from baseline at Week 4 | -21.5 score on a scale | Standard Deviation 16.3 |
Secondary
Change From Baseline in the Visual Analog Scale Symptoms Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACT-774312 | 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 |
| ACT-774312 | 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 |
| ACT-774312 | 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 |
| ACT-774312 | 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 |
| ACT-774312 | Change From Baseline in the Visual Analog Scale Symptoms Score | Baseline | 304.0 score on a scale | Standard Deviation 75 |
| ACT-774312 | 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 |
| Placebo | Change From Baseline in the Visual Analog Scale Symptoms Score | Baseline | 323.5 score on a scale | Standard Deviation 95.5 |
| Placebo | Change From Baseline in the Visual Analog Scale Symptoms Score | Change from baseline at Week 4 | -58.0 score on a scale | Standard Deviation 18.4 |
| Placebo | Change From Baseline in the Visual Analog Scale Symptoms Score | Change from baseline at Week 16 (End-of-Study) | -57.0 score on a scale | Standard Deviation 104.7 |
| Placebo | Change From Baseline in the Visual Analog Scale Symptoms Score | Change from baseline at Week 8 | -88.5 score on a scale | Standard Deviation 61.5 |
| Placebo | Change From Baseline in the Visual Analog Scale Symptoms Score | Change from baseline at Week 2 | -77.5 score on a scale | Standard Deviation 136.5 |
| Placebo | Change From Baseline in the Visual Analog Scale Symptoms Score | Change from baseline at Week 12 | -156.0 score on a scale | Standard Deviation 123.7 |
Secondary
Change From Baseline to Week 12 in Sinus Opacifications as Assessed by Computed Tomography Scan Using the Modified Lund Mackay Score (Assessed Centrally)
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.
Time frame: Pre-dose (Baseline on Day 1) and Week 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ACT-774312 | 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 |
| Placebo | Change From Baseline to Week 12 in Sinus Opacifications as Assessed by Computed Tomography Scan Using the Modified Lund Mackay Score (Assessed Centrally) | 4.84 score on a scale | Standard Error 1.96 |
p-value: =0.16195% CI: [-10.41, 2.45]ANCOVA
Secondary
Change From Baseline to Week 12 in the Left Maxillary Sinus Mucosal Volume
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.
Time frame: Pre-dose (Baseline on Day 1) and Week 12
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACT-774312 | Change From Baseline to Week 12 in the Left Maxillary Sinus Mucosal Volume | -1.72 milliliter(s) | Standard Deviation 1.72 |
| Placebo | Change From Baseline to Week 12 in the Left Maxillary Sinus Mucosal Volume | -1.08 milliliter(s) | Standard Deviation 2.48 |
Secondary
Change From Baseline to Week 12 in the Right Maxillary Sinus Mucosal Volume
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.
Time frame: Pre-dose (Baseline on Day 1) and Week 12
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACT-774312 | Change From Baseline to Week 12 in the Right Maxillary Sinus Mucosal Volume | 0.94 milliliter(s) | Standard Deviation 4.36 |
| Placebo | Change From Baseline to Week 12 in the Right Maxillary Sinus Mucosal Volume | -1.78 milliliter(s) | Standard Deviation 1.34 |
Secondary
Change From Baseline to Week 12 in the University of Pennsylvania Smell Identification Test
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.
Time frame: Pre-dose (Baseline on Day 1) and Week 12
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACT-774312 | Change From Baseline to Week 12 in the University of Pennsylvania Smell Identification Test | 1.0 score on a scale | Standard Deviation 8.4 |
| Placebo | Change From Baseline to Week 12 in the University of Pennsylvania Smell Identification Test | -0.5 score on a scale | Standard Deviation 0.7 |
Secondary
Change From Baseline to Week 12 in the Volume of Air in the Left Maxillary Sinus
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.
Time frame: Pre-dose (Baseline on Day 1) and Week 12
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACT-774312 | Change From Baseline to Week 12 in the Volume of Air in the Left Maxillary Sinus | 1.17 milliliter(s) | Standard Deviation 1.72 |
| Placebo | Change From Baseline to Week 12 in the Volume of Air in the Left Maxillary Sinus | -1.08 milliliter(s) | Standard Deviation 2.48 |
Secondary
Change From Baseline to Week 12 in the Volume of Air in the Right Maxillary Sinus
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.
Time frame: Pre-dose (Baseline on Day 1) and Week 12
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACT-774312 | Change From Baseline to Week 12 in the Volume of Air in the Right Maxillary Sinus | -0.94 milliliter(s) | Standard Deviation 4.36 |
| Placebo | Change From Baseline to Week 12 in the Volume of Air in the Right Maxillary Sinus | 1.77 milliliter(s) | Standard Deviation 1.34 |
Secondary
Patient Global Impression of Change in Disease Severity
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACT-774312 | Patient Global Impression of Change in Disease Severity | Week 16 (End-of-Study) | 3.4 score on a scale | Standard Deviation 0.9 |
| ACT-774312 | Patient Global Impression of Change in Disease Severity | Week 4 | 3.0 score on a scale | Standard Deviation 0.7 |
| ACT-774312 | Patient Global Impression of Change in Disease Severity | Week 2 | 3.2 score on a scale | Standard Deviation 0.4 |
| ACT-774312 | Patient Global Impression of Change in Disease Severity | Week 8 | 3.4 score on a scale | Standard Deviation 1.5 |
| ACT-774312 | Patient Global Impression of Change in Disease Severity | Week 12 | 3.4 score on a scale | Standard Deviation 0.5 |
| Placebo | Patient Global Impression of Change in Disease Severity | Week 8 | 2.0 score on a scale | Standard Deviation 0 |
| Placebo | Patient Global Impression of Change in Disease Severity | Week 12 | 2.0 score on a scale | Standard Deviation 0 |
| Placebo | Patient Global Impression of Change in Disease Severity | Week 16 (End-of-Study) | 2.5 score on a scale | Standard Deviation 0.7 |
| Placebo | Patient Global Impression of Change in Disease Severity | Week 2 | 2.5 score on a scale | Standard Deviation 2.1 |
| Placebo | Patient Global Impression of Change in Disease Severity | Week 4 | 2.5 score on a scale | Standard Deviation 2.1 |
Secondary
Physician Global Assessment of Change in Disease Severity
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACT-774312 | Physician Global Assessment of Change in Disease Severity | Week 4 | 3.0 score on a scale | Standard Deviation 0.7 |
| ACT-774312 | Physician Global Assessment of Change in Disease Severity | Week 12 | 3.4 score on a scale | Standard Deviation 0.5 |
| ACT-774312 | Physician Global Assessment of Change in Disease Severity | Week 8 | 3.6 score on a scale | Standard Deviation 1.3 |
| ACT-774312 | Physician Global Assessment of Change in Disease Severity | Week 16 (End-of-Study) | 3.6 score on a scale | Standard Deviation 0.5 |
| ACT-774312 | Physician Global Assessment of Change in Disease Severity | Week 2 | 3.4 score on a scale | Standard Deviation 0.5 |
| Placebo | Physician Global Assessment of Change in Disease Severity | Week 16 (End-of-Study) | 4.0 score on a scale | Standard Deviation 1.4 |
| Placebo | Physician Global Assessment of Change in Disease Severity | Week 2 | 3.0 score on a scale | Standard Deviation 1.4 |
| Placebo | Physician Global Assessment of Change in Disease Severity | Week 4 | 3.0 score on a scale | Standard Deviation 1.4 |
| Placebo | Physician Global Assessment of Change in Disease Severity | Week 8 | 2.5 score on a scale | Standard Deviation 0.7 |
| Placebo | Physician Global Assessment of Change in Disease Severity | Week 12 | 4.0 score on a scale | Standard Deviation 1.4 |