A Study to Evaluate the Effect of ACT-774312 in Subjects With Bilateral Nasal Polyposis
Condition: Bilateral Nasal Polyposis
MeSH terms: Colorectal Neoplasms; Nasopharyngeal Neoplasms; Nasal Polyps
Intervention: ACT-774312; Placebo
Intervention description: ACT-774312 will be available as hard gelatin capsules containing 200 mg of ACT-774312; Matching placebo hard gelatin capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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).