A Study to Evaluate the Effect of ACT-774312 in Subjects With Bilateral Nasal Polyposis

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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).