A Study to Assess the Effectiveness, Safety, and Tolerability of Brensocatib in Participants with Non-Cystic Fibrosis Bronchiectasis (ASPEN)

Overview

About this study

The purpose of this study is to evaluate the effect of brensocatib at 10 mg and 25 mg compared with placebo on the rate of pulmonary exacerbations (PEs) over the 52-week treatment period.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Provide their signed study informed consent to participate.
  • Male or female ≥ 18 years and ≤ 85 years of age (inclusive) at screening.
  • BMI ≥ 18.5 at screening.
  • Clinical history consistent with NCFBE (cough, chronic sputum production and/or recurrent respiratory infections) that is confirmed by chest CT demonstrating bronchiectasis affecting one or more lobes (confirmation may be based on prior chest CT):
    • For each subject, the most recent chest CT scan (but not older than 5 years before the Screening date) will be selected for transfer to the central reading facility for confirmation of the diagnosis of NCFBE;
    • If the CT scan cannot be read by the reviewers due to quality issues, a new high-resolution CT scan will be performed;
    • In case a chest CT scan in the last 5 years is not available, a new high-resolution chest CT scan must be obtained for confirmation of the diagnosis of NCFBE by the central reading facility.
  • Postbronchodilator FEV1 at the Screening Visit ≥ 30% of predicted normal value, calculated using National Health and Nutrition Examination Survey reference equations and must have an absolute value ≥ 750 mL.
  • Current sputum producer with a history of chronic expectoration of at least 3 months in the past 12 months, and able to provide sputum sample during screening (Visit 1). If a subject is unable to produce sputum spontaneously during screening, the subject will be considered a screen failure. The subject should not undergo a sputum induction procedure during screening to meet inclusion criterion.
  • Mucopurulent or purulent sputum color assessed at the Screening Visit by color chart developed by MP Murray (Murray et al., 2009).
  • At least 2 pulmonary exacerbations defined by need for antibiotic prescription by a physician for the signs and symptoms of respiratory infections in the past 12 months before the Screening Visit.
  • Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, or using highly effective contraception (i.e., methods that can achieve a failure rate < 1% per year when used consistently and correctly) from Day 1 to at least 90 days after the last dose. Such methods include true abstinence (refraining from heterosexual intercourse during the study); combined (estrogen and progestogen-containing) or progestogen-only hormonal contraception associated with inhibition of ovulation and supplemented with a double barrier (preferably male condom); intrauterine devices; intrauterine hormone-releasing systems; or vasectomized partner. The Investigator or designee should explain the acceptable methods of birth control to the subject, and instruct the subject to follow the direction. For WOCBP ≤ 45 years of age, testing of FSH level should be performed; a threshold of > 40 mIU/mL should be met to be considered infertile.
    • Note: Abstinence is only considered to be a highly effective method of contraception when this is the preferred and usual lifestyle of a subject. Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
  • Male subjects with female partners of childbearing potential must be using effective contraception from Day 1 to at least 90 days after the last dose. Acceptable methods include true abstinence (refraining from intercourse during the study), combined (estrogen and progestogen-containing) or progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormonereleasing systems.
  • Male subjects with pregnant or non-pregnant WOCBP partners must use condoms to avoid potential exposure to the embryo/fetus.

Exclusion Criteria:

  • A primary diagnosis of COPD or asthma as judged by the Investigator. Patients with comorbid COPD and/or asthma can be enrolled if bronchiectasis is their primary diagnosis.
  • Subjects receiving supplemental oxygen > 12 hours per day.
  • Bronchiectasis due to cystic fibrosis.
  • Current smokers as defined per CDC: an adult who has smoked 100 cigarettes in his or her lifetime and who currently smokes cigarettes.
  • No evidence of bronchiectasis according to the BE-CT scoring system.
  • Known or suspected immunodeficiency disorder, including history of invasive opportunistic infections (e.g., TB, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency, or prolonged infections suggesting an immunecompromised status, as judged by the Investigator.
  • Known history of HIV infection.
  • Established diagnosis of hepatitis B viral infection at the time of screening, or positive for HBsAg at the time of screening.
  • Subjects who have gained immunity for hepatitis B virus infection after vaccination (subjects who are HBsAg-negative, HBsAb-positive, and HBcAb-negative are eligible for the study). Subjects with positive HBcAb are eligible for the study only if hepatitis B virus DNA level is undetectable.
  • Established diagnosis of HCV infection at the time of Screening. Subjects positive for hepatitis C antibody are eligible for the study only if HCV RNA is negative.
  • Currently being treated for NTM lung infection, allergic bronchopulmonary aspergillosis, or TB.
  • Active and current symptomatic infection by COVID-19.
  • Unable to perform technically acceptable spirometry that meet the ATS/ERS acceptability criteria with at least 3 acceptable flow-volume curves, at least 2 of which meet the ATS/ERS repeatability criteria for FEV1 during Screening.
  • Inability to follow the procedures of the study (eg, due to language problems or psychological disorders).
  • Receiving medications or therapy that are prohibited as concomitant medications:
    • Started oral or inhaled antibiotics as chronic treatment for NCFBE for 2 × ULN);
    • Bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%);
    • Known hepatic or biliary abnormalities, not including Gilbert's syndrome or asymptomatic gallstones.
  • History of malignancy in the past 5 years, except completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin.
  • Previously participated in a clinical trial of brensocatib.
  • An absolute neutrophil count < 1,000/mm^3 at the Screening Visit.
  • 3. Received any live attenuated vaccine within 4 weeks prior to the first administration of brensocatib. If a live vaccine has been administered the subject should wait 4 weeks prior to Screening. During the study, subjects may not receive any live attenuated vaccine.
  • Significant hemoptysis (≥ 300 mL or requiring blood transfusion) within 6 weeks prior to the Screening Visit or during the Screening Period.
  • Have diagnosed periodontal disease and are either:
    • Under active management by a dentist for this condition; or
    • Are expected to have periodontal disease-related procedures within the study period.
  • Suffering an exacerbation 4 weeks before Screening or during the Screening Period. In this case, subjects will be considered a screen failure. Subjects are eligible for rescreen only after recovery and 4 weeks after last dose of antibiotic treatment.
  • Have compliance issues with completion of electronic diary entries (< 75%) during the Screening Period AND in the opinion of the Investigator, compliance is unlikely to improve during the study.
  • Participated in any other interventional clinical studies within 3 months before Screening Visit.
  • Clinical diagnosis of Papillon-Lefèvre Syndrome.
  • Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the subject's participation in the study. Examples include but are not limited to short life expectancy, uncontrolled diabetes, cardiovascular conditions (e.g., NYHA Class III or IV cardiac failure), severe renal conditions (e.g., severe nephrotic syndrome), hepatobiliary conditions (e.g., Child-Pugh class B or C), neurological conditions (e.g., demyelinating diseases), active major autoimmune diseases (e.g., lupus, inflammatory bowel disease, rheumatoid arthritis, etc.), other severe endocrinologic, gastrointestinal, metabolic, pulmonary, or lymphatic diseases. The specific justification for subjects excluded under this criterion will be noted in study documents (chart notes, CRF, etc.).
  • Any clinically significant abnormal laboratory values at Screening or diseases or disorders (eg, survivors of severe COVID-19 disease including ARDS, cardiovascular, pulmonary, gastrointestinal, liver, kidney, neurological, musculoskeletal, endocrine, metabolic, psychiatric, physical impairment, or a lung transplantation) that, in the opinion of the Investigator, may put the subject at risk by participating in the study, or interfere with the subject's treatment, assessment, or influence the results of the study, or have compliance issues with the study or have a planned or anticipated major surgical procedure during the study.
  • History of alcohol or drug abuse within 6 months prior to the Screening Visit.
  • Any other medical or psychological condition including relevant laboratory abnormalities at screening that, in the opinion of the Investigator, suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study subject as a result of his/her participation in this clinical trial, may make subject’s participation unreliable, or may interfere with study assessments. The specific justification for subjects excluded under this criterion will be noted in study documents.
  • Is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study.
  • Known history of hypersensitivity to brensocatib or any of its excipients.

Eligibility last updated 9/21/21.  Questions regarding updates should be directed to the study team contact.

 

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Timothy Aksamit, M.D.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Kayla MacDonald

(507) 538-0595

MacDonald.Kayla@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20510854

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