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Trial record 1 of 1 for:    03218917
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Assessment of INS1007 in Subjects With Non-Cystic Fibrosis Bronchiectasis

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ClinicalTrials.gov Identifier: NCT03218917
Recruitment Status : Completed
First Posted : July 17, 2017
Last Update Posted : December 14, 2020
Sponsor:
Information provided by (Responsible Party):
Insmed Incorporated

Tracking Information
First Submitted Date  ICMJE July 11, 2017
First Posted Date  ICMJE July 17, 2017
Last Update Posted Date December 14, 2020
Actual Study Start Date  ICMJE December 1, 2017
Actual Primary Completion Date December 12, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2017)
Time to first pulmonary exacerbation [ Time Frame: 24-week treatment period ]
Exacerbation is defined by signs and symptoms plus intervention with systemic antibiotics.
Original Primary Outcome Measures  ICMJE
 (submitted: July 12, 2017)
Time to first pulmonary exacerbation [ Time Frame: 24-week treatment period ]
Time to first pulmonary exacerbation (defined as 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics: increased cough; increased sputum volume or change in sputum consistency; increased sputum purulence; increased breathlessness and/or decreased exercise tolerance; fatigue and/or malaise; hemoptysis. Subjects on chronic macrolide therapy whose only change in therapy is dose or frequency adjustment will not meet the definition of exacerbation.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2017)
  • Rate of pulmonary exacerbations [ Time Frame: 24-week treatment period ]
    Number of events per person-time over 24-weeks.
  • Change from Baseline in the Respiratory Symptoms Domain Score of the Quality of Life (QOL) Bronchiectasis questionnaire [ Time Frame: 24-week treatment period ]
    Change from Baseline symptom score at 24-weeks.
  • Change from Screening in post-bronchodilator forced expiratory volume in 1 second (FEV1) [ Time Frame: 24-week treatment period ]
    Change from Screening in FEV1 at 24-weeks.
  • Change in concentration of active neutrophil elastase (NE) in sputum from pre-treatment to on treatment [ Time Frame: 24-week treatment period ]
    Change in concentration of active NE in sputum from pretreatment defined as as the average of Screening and Day 1 concentrations) to on-treatment (defined as the average of Week 12 and Week 24 concentrations).
Original Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2017)
  • Change from Baseline in Quality of Life (QOL)-B respiratory symptoms [ Time Frame: 24-week treatment period ]
    Change from in the QOL-B respiratory symptom score from Baseline to end of study drug administration at 24-weeks
  • Change from Screening in post-bronchodilator forced expiratory volume in 1 second (FEV1) to the end of the 24 week treatment period [ Time Frame: 24-week treatment period ]
    Change in FEV1 from Screening to the end of the 24-week treatment period
  • Change from Baseline in active neutrophil elastase (NE) sputum concentrations [ Time Frame: 24-week treatment period ]
    Change in concentration of active NE in sputum from Baseline (defined as as the average of Screening and Day 1 concentrations) to the end of the study drug administration at Week 24 (defined as the average of Week 12 and Week 24 concentrations)
  • Rate of pulmonary exacerbations measured as the number of events per person over the duration of study treatment (24 weeks) [ Time Frame: 24-week treatment period ]
    Number of events of pulmonary exacerbations per person-time over the duration of study drug administration (24-week treatment period)
Current Other Pre-specified Outcome Measures
 (submitted: August 15, 2017)
  • Change from Baseline in QOL-B scores (excluding Respiratory Symptoms Domain) [ Time Frame: 24-week treatment period ]
    Change from Baseline in score of QOL-B domains (excluding respiratory symptoms domain) at 24-weeks.
  • Change from Baseline in Leicester Cough Questionnaire (LCQ) score [ Time Frame: 24-week treatment period ]
    Change from Baseline in LCQ score at 24-weeks.
  • Change from Baseline in St. George's Respiratory Questionnaire (SGRQ) score [ Time Frame: 24-week treatment period ]
    Change from Baseline in SGRQ total score at 24- weeks.
  • Change from Screening of forced vital capacity (FVC) [ Time Frame: At Week 12 and Week 24 ]
    Change from Screening of FVC at Weeks 12 and 24.
  • Change from Screening of peak expiratory flow rate (PEFR) [ Time Frame: At Week 12 and Week 24 ]
    Change from Screening of PEFR at Weeks 12 and 24.
  • Change from Screening of forced exploratory flow 25% to 75% (FEF25-75) [ Time Frame: At Week 12 and Week 24 ]
    Change from Screening in FEF25-75 at Weeks 12 and 24.
Original Other Pre-specified Outcome Measures
 (submitted: July 12, 2017)
  • Change in QOL-B domains [ Time Frame: 24-week treatment period ]
    Change from Baseline in score of QOL-B domains (excluding respiratory symptoms domain) over the 24-week treatment period
  • Change in Leicester Cough Questionnaire (LCQ) score [ Time Frame: 24-week treatment period ]
    Change from Baseline in LCQ score over the 24-week treatment period
  • Change in St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: 24-week treatment period ]
    Change from Baseline in SGRQ total score over the 24-week treatment period
  • Change in concentration of active neutrophil elastase (NE) in sputum from pre-treatment (Baseline) to pre-specified treatment and post-treatment time points [ Time Frame: 24-week treatment period and Week 28 ]
    Change in concentration of active NE in sputum from Baseline (pre-treatment) to Weeks 2, 4, and 28 (4-weeks after the end of study treatment)
  • Change in concentration of active neutrophil elastase (NE) in blood from pre-treatment (Baseline) to pre-specified treatment and post-treatment time points [ Time Frame: 24-week treatment period and Week 28 ]
    Change in concentration of active NE in reagent-stimulated blood from Baseline (pre-treatment) to Weeks 2, 4, 12, 24, and 28 (4-weeks after the end of study treatment)
  • Change in sputum color from Baseline to pre-specified treatment and post-treatment time points [ Time Frame: 24-week treatment period and Week 28 ]
    Change from Baseline in sputum color (assessed by Sputum color chart) at Weeks 2, 4, 12, 24, and 28 (4-weeks after the end of study treatment)
  • Change in inflammatory and tissue degradation biomarker levels from Baseline to pre-specified treatment and post-treatment time points [ Time Frame: 24-week treatment period and Week 28 ]
    Change from Baseline in inflammatory and tissue degradation biomarker levels in blood at Weeks 2, 4, 12, 24, and 28 (4 weeks after the end of study treatment) The biomarkers that may be explored consist of absolute neutrophil count, proteinase 3, and cathepsin G.
  • Change from Baseline in desmosine concentrations in urine at pre-specified treatment and post-treatment time points [ Time Frame: 24-week treatment period and Week 28 ]
    Change from Baseline in tissue degradation biomarker level of desmosine in urine at Weeks 2, 4, 12, 24, and 28 (4 weeks after the end of study treatment)
  • Change from Screening in forced vital capacity (FVC) to pre-specified treatment time points [ Time Frame: 24-week treatment period ]
    Change from Screening in FVC at Weeks 12 and 24
  • Change in peak expiratory flow rate (PEFR) to pre-specified treatment time points [ Time Frame: 24-week treatment period ]
    Change from Screening of PEFR at Weeks 12 and 24.
  • Change from Screening in forced expiratory flow between 25 and 75% of forced vital capacity (FEF25-75) to pre-specified treatment time points [ Time Frame: 24-week treatment period ]
    Change from Screening in FEF25-75 at Weeks 12 and 24.
  • Duration of exacerbations per subject per day during the 24-week treatment period. [ Time Frame: 24-week treatment period ]
    Total duration (in days) exacerbations, per subject, over the 24-week treatment period
  • Frequency of use of rescue medications [ Time Frame: 24-week treatment period ]
    Frequency of use of rescue medications over the 24-week treatment period (rescue medications include short-acting beta agonists (SABA), short-acting muscarinic antagonists (SAMA), newly prescribed long-acting beta-agonists (LABA), long-acting muscarinic antagonists (LAMA), and oxygen).
  • Number of hospitalizations [ Time Frame: 24-week treatment period ]
    Number of subjects hospitalized due to pulmonary exacerbations by the end of the 24-week treatment period
  • Incidence of Treatment-Emergent Adverse Events (TEAEs) including results from electrocardiograms, clinical laboratories, vital signs, physical exam, and pulmonary function [ Time Frame: 24-week treatment period ]
    Safety endpoints will include: adverse events, 12-lead electrocardiogram measurements, clinical laboratory testing results, vital sign measurements, physical examination results, and pulmonary function test (PFT) assessed throughout the study treatment period. Adverse events of special interest will be hyperkeratosis, periodontitis/gingivitis and other infections
  • Pharmacokinetic substudy - maximum plasma concentration (Cmax) [ Time Frame: Study Visits 2, 3, 6, 9, and 10 ]
    INS1007 Cmax , as estimated using non-compartmental analysis methods will be assessed in a substudy of a maximum of 36 subjects at pre-specified time points during the study treatment period
  • Pharmacokinetic substudy - time to maximum plasma concentration (Tmax) [ Time Frame: Study Visits 2, 3, 6, 9, and 10 ]
    INS1007 Tmax , as estimated using non-compartmental analysis methods will be assessed in a substudy of a maximum of 36 subjects at pre-specified time points during the study treatment period
  • Pharmacokinetic substudy - average plasma concentration at steady state (Css) [ Time Frame: Study Visits 2, 3, 6, 9, and 10 ]
    INS1007 Css , as estimated using non-compartmental analysis methods will be assessed in a substudy of a maximum of 36 subjects at pre-specified time points during the study treatment period
  • Pharmacokinetic substudy - maximum plasma concentration at steady state (Cmaxss) [ Time Frame: Study Visits 2, 3, 6, 9, and 10 ]
    INS1007 Cmaxss , as estimated using non-compartmental analysis methods will be assessed in a substudy of a maximum of 36 subjects at pre-specified time points during the study treatment period
  • Pharmacokinetic substudy - Time to maximum plasma concentration at steady state (Tmaxss) [ Time Frame: Study Visits 2, 3, 6, 9, and 10 ]
    INS1007 Tmaxss , as estimated using non-compartmental analysis methods will be assessed in a substudy of a maximum of 36 subjects at pre-specified time points during the study treatment period
  • Pharmacokinetic substudy - minimum plasma concentration (Cmin) [ Time Frame: Study Visits 2, 3, 6, 9, and 10 ]
    INS1007 Cmin , as estimated using non-compartmental analysis methods will be assessed in a substudy of a maximum of 36 subjects at pre-specified time points during the study treatment period
  • Pharmacokinetic substudy - minimum plasma concentration at steady state (Cminss) [ Time Frame: Study Visits 2, 3, 6, 9, and 10 ]
    INS1007 Cminss , as estimated using non-compartmental analysis methods will be assessed in a substudy of a maximum of 36 subjects at pre-specified time points during the study treatment period
  • Pharmacokinetic substudy - area under the plasma concentration curve from 0 to 8 hours (AUC0-8) [ Time Frame: Study Visits 2, 3, 6, 9, and 10 ]
    INS1007 AUC0-8 , as estimated using non-compartmental analysis methods will be assessed in a substudy of a maximum of 36 subjects at pre-specified time points during the study treatment period
 
Descriptive Information
Brief Title  ICMJE Assessment of INS1007 in Subjects With Non-Cystic Fibrosis Bronchiectasis
Official Title  ICMJE Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Study to Assess the Efficacy, Safety & Tolerability, and PK of INS1007 Administered Once Daily for 24 Weeks in Subjects With Non-CF Bronchiectasis - The Willow Study
Brief Summary The purpose of the study is to evaluate if INS1007 can reduce pulmonary exacerbations over a 24-week treatment period in patients with non-cystic fibrosis bronchiectasis.
Detailed Description Phase 2 randomized, double-blind, placebo-controlled, parallel-group, multicenter, multi-national study to assess the efficacy, safety and tolerability, and pharmacokinetics (PK) of INS1007 administered once daily for 24 weeks in subjects with non-cystic fibrosis bronchiectasis (NCFBE).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non-Cystic Fibrosis Bronchiectasis
Intervention  ICMJE
  • Drug: INS1007 10 mg oral tablet
    Administered once per day for 24 weeks
  • Drug: INS1007 25 mg oral tablet
    Administered once per day for 24 weeks
  • Drug: Placebo Oral Tablet
    Administered once per day for 24 weeks
Study Arms  ICMJE
  • Experimental: INS1007 10 mg Oral Tablet
    Once per day for 24 weeks.
    Intervention: Drug: INS1007 10 mg oral tablet
  • Experimental: INS1007 25 mg Oral Tablet
    Once per day for 24 weeks.
    Intervention: Drug: INS1007 25 mg oral tablet
  • Placebo Comparator: Placebo Oral Tablet
    Once per day for 24 weeks.
    Intervention: Drug: Placebo Oral Tablet
Publications * Chalmers JD, Haworth CS, Metersky ML, Loebinger MR, Blasi F, Sibila O, O'Donnell AE, Sullivan EJ, Mange KC, Fernandez C, Zou J, Daley CL; WILLOW Investigators. Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. N Engl J Med. 2020 Nov 26;383(22):2127-2137. doi: 10.1056/NEJMoa2021713. Epub 2020 Sep 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 17, 2019)
256
Original Estimated Enrollment  ICMJE
 (submitted: July 12, 2017)
240
Actual Study Completion Date  ICMJE December 12, 2019
Actual Primary Completion Date December 12, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Clinical history consistent with NCFBE (cough, chronic sputum production and/or recurrent respiratory infections)
  2. Are current sputum producers with a history of chronic expectoration and able to provide a sputum sample during Screening
  3. Have at least 2 documented pulmonary exacerbations in the past 12 months before Screening

Exclusion Criteria:

  1. Have a primary diagnosis of chronic obstructive pulmonary disease (COPD) or asthma
  2. Have bronchiectasis due to cystic fibrosis (CF), hypogammaglobulinemia, common variable immunodeficiency, or alpha1-antitrypsin deficiency
  3. Are current smokers
  4. Are currently being treated for a nontuberculous mycobacterial lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis
  5. Have any acute infections, (including respiratory infections)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Bulgaria,   Denmark,   Germany,   Italy,   Korea, Republic of,   Netherlands,   New Zealand,   Poland,   Singapore,   Spain,   United Kingdom,   United States
Removed Location Countries Sweden
 
Administrative Information
NCT Number  ICMJE NCT03218917
Other Study ID Numbers  ICMJE INS1007-201
2017-002533-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Insmed Incorporated
Study Sponsor  ICMJE Insmed Incorporated
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Carlos Fernandez, MD Insmed Incorporated
PRS Account Insmed Incorporated
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP