A Study to Assess the Efficacy and Safety of Study Drug INS1007 Administered Once Daily in Patients with Non-Cystic Fibrosis

• Register: EUCTR
• Last refreshed on: 16 November 2020
• Main ID: EUCTR2017-002533-32-IT
• Date of registration: 05/11/2020
• Prospective Registration: No
• Primary sponsor: INSMED INCORPORATED
• Public title: A Study to Assess the Efficacy and Safety of Study Drug INS1007 Administered Once Daily in Patients with Non-Cystic Fibrosis
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Study to Assess the Efficacy, Safety and Tolerability, and Pharmacokinetics of INS1007 Administered Once Daily for 24 Weeks in Subjects with Non-Cystic Fibrosis Bronchiectasis - The Willow Study - N/A
• Date of first enrolment: 23/01/2018
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002533-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Bulgaria, Denmark, Germany, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Singapore, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Clinical trial contact
• Affiliation: Insmed Incorporated

• Name: Clinical trial contact
• Affiliation: Insmed Incorporated

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects who have given their signed, informed consent, are male or female between 18 and 85 years of age (inclusive) with a body mass index > 18.5 at Screening (Visit 1) and have a clinical history consistent with NCFBE will be eligible for enrollment in the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 96
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 144

Exclusion criteria:
Subjects who have a primary diagnosis of chronic obstructive pulmonary disease or asthma, have bronchiectasis due to cystic fibrosis, hypogammaglobulinemia, common variable immunodeficiency, or a1-antitrypsin deficiency, are current smokers as defined per Centers for Disease Control and Prevention criteria, or currently being treated for a nontuberculous mycobacterial lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis will not be eligible for enrollment in the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Non-Cystic Fibrosis Bronchiectasis
MedDRA version: 20.0 Level: SOC Classification code 10038738 Term: Respiratory, thoracic and mediastinal disorders System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 21.0 Level: PT Classification code 10006445 Term: Bronchiectasis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: INS1007
Product Code: [N/A]
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: INS1007
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: INS1007
Product Code: [N/A]
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: INS1007
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The time to the first pulmonary exacerbation over the 24-week treatment period.

Main Objective: To evaluate the effect of INS1007 compared with placebo on time to first pulmonary exacerbation over the 24-week treatment period.
To assess the safety and tolerability of INS1007 relative to placebo based on adverse events (AEs), vital signs and electrocardiogram (ECG) measurements, physical exams and clinical laboratory evaluations.

Secondary Objective: 1. To evaluate the effect of INS1007 compared with placebo on quality of life (QOL), as assessed by the Quality of Life Questionnaire-Bronchiectasis (QOL-B), Respiratory Symptoms Domain score, over the 24-week treatment period.
2. To evaluate the effect of INS1007 compared with placebo on lung function, as measured by forced expiratory volume in 1 second (FEV1), over the 24-week treatment period.
3. To evaluate the effect of INS1007 compared with placebo on the concentration of active neutrophil elastase (NE) in sputum, as measured by the difference between the pre-treatment concentration (defined as the average of the values at Screening and Day 1) and on-treatment concentration (defined as the average of the values at weeks 12 and 24).
4. To evaluate the effect of INS1007 compared with placebo on the rate of pulmonary exacerbations over the 24-week treatment period.

Primary end point(s): The primary endpoint is the time to the first pulmonary exacerbation over the 24-week treatment period.
Pulmonary exacerbation definition - A pulmonary exacerbation in this study is defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics.
1. Increased cough;
2. Increased sputum volume or change in sputum consistency;
3. Increased sputum purulence;
4. Increased breathlessness and/or decreased exercise tolerance;
5. Fatigue and/or malaise;
6. Hemoptysis.
Subjects on chronic macrolide therapy whose only change in therapy is dose or frequency adjustment will not meet the definition of exacerbation.

Secondary Outcome(s)

Secondary end point(s): 1. Change from Baseline in QOL-B Respiratory Symptoms Domain score over the 24-week treatment period.
2. Change from Screening in post-bronchodilator FEV1 over the 24-week treatment period.
3. Change in concentration of active NE in sputum from pre-treatment (defined as the average of Screening and Day 1 concentrations) to ontreatment (defined as the average of Week 12 and Week 24 concentrations).
4. Rate of pulmonary exacerbations (number of events per person-time) over the 24-week treatment period.

Timepoint(s) of evaluation of this end point: Over the 24-week treatment period.

Secondary ID(s)

NCT03218917

INS1007-201

2017-002533-32-GB

Source(s) of Monetary Support

Insmed Incorporated

Ethics review

Status: Approved
Approval date: 09/01/2018
Contact: