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

• Status: Completed
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Idorsia Pharmaceuticals Ltd.
• Treatments: Mometasone Furoate

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 subjects 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 predose 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 < 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 subject.

• Subject with severe renal function impairment (≤ 29 mL/min/1.73 m2) which is defined by eGFR estimated at screening using the Modification of Diet in Renal Disease (MDRD) formula.

• Subject with Sino-Nasal Outcome Test (SNOT-22) <20.

• Subject 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.

• Subject who has required INCS drops within the 6 weeks before screening.

• Subject 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.

• Subject who has undergone any nasal surgery within 6 months before screening.

• Subjects with conditions/concomitant diseases making them nonevaluable 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.

• Subjects 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.

• Subject 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).

• Subject considered as vulnerable (e.g., sponsor or site employee, investigator subordinate, subject incapable of giving consent, subject committed to an institution by way of official or judicial order).

• Subject with liver injury related criteria:

• Underlying hepatobiliary disease OR

• ALT>3 ULN OR

• or Bilirubin>2 ULN.