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

NCT03688555 | Completed Phase 2 Results

• 2 other identifiers: ID-084A2012018-000851-42
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 2

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

Conditions

Bilateral Nasal Polyposis

Outcome Measures

Primary Outcomes (1)

• 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.

  Pre-dose (Baseline on Day 1) and Week 12

Secondary Outcomes (10)

• 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

• 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

• 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

• Change From Baseline to Week 12 in the Left Maxillary Sinus Mucosal Volume

  Pre-dose (Baseline on Day 1) and Week 12

• Change From Baseline to Week 12 in the Right Maxillary Sinus Mucosal Volume

  Pre-dose (Baseline on Day 1) and Week 12

Study Arms (2)

ACT-774312

EXPERIMENTAL

Participants will receive ACT-774312 (400 mg twice daily) in the morning and evening with or without food for 12 weeks together with mometasone furoate nasal spray.

Drug: ACT-774312

Placebo

PLACEBO COMPARATOR

Participants will receive placebo twice daily in the morning and evening with or without food for 12 weeks together with mometasone furoate nasal spray.

Drug: Placebo

Interventions

ACT-774312 DRUG

ACT-774312 will be available as hard gelatin capsules containing 200 mg of ACT-774312

ACT-774312

Placebo DRUG

Matching placebo hard gelatin capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (2)

University Hospital Ghent

Ghent, 9000, Belgium

Location

Charité Research Organisation GmbH

Berlin, 10117, Germany

Location

MeSH Terms

Interventions

ACT-774312

Limitations and Caveats

The study was initially planned as a single-center study. The protocol had to be updated accordingly for approvals for the second site in Germany. The p-values need to be cautiously interpreted due to the small study population size. Recruitment was put on hold on during the COVID-19 pandemic from 30 March to 28 May 2020 in Germany and from 31 March 2020 to 11 June 2020 in Belgium. Recruitment was subsequently restarted.

Results Point of Contact

• Title: Clinical Trials Disclosure Desk
• Organization: Idorsia Pharmaceuticals Ltd

clinical-trials-disclosure@idorsia.com

+41 588 441977

Study Officials

• Clinical Trials

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 28, 2018
• Study Start: October 19, 2018
• Primary Completion: November 24, 2020
• Study Completion: December 1, 2020
• Last Updated: April 11, 2022
• Results First Posted: February 1, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); DE (1)