Clinical trial NCT05090904: A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Brensocatib Tablets in Adults With Cystic Fibrosis
Official title: A Phase 2a, Single-Blind, Placebo-Controlled, Parallel-Group Study to Assess Safety, Tolerability, and Pharmacokinetics of Brensocatib Tablets in Adults With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Brensocatib
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2021-10-25
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of the study is to evaluate the pharmacokinetics of brensocatib in participants with cystic fibrosis following once daily oral administration of study drug and to evaluate the safety of brensocatib compared to placebo in participants with cystic fibrosis (CF) over the 4-week treatment period.


Eligibility criteria: Inclusion Criteria:

* Participants must be ≥18 years of age at the time of signing the informed consent.
* Male or female participants with a confirmed diagnosis of CF related lung disease:

  1. Percent predicted forced expiratory volume in 1 second (ppFEV1) between 40% to 90% (inclusive) at Screening Visit and at Baseline.
  2. Stable CF treatment for at least 30 days before screening and willing to remain on a stable regimen throughout the treatment period.
* Has a body mass index ≥18 kg/m\^2.
* Male and female participants must use contraceptives that are consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

  1. Male participants, who are not sterile, with female partners of childbearing potential must be using effective contraception from Day 1 to at least 90 days after the last dose.
  2. Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, or using highly effective contraception methods (i.e., methods that alone or in combination achieve \<1% unintended pregnancy rates per year when used consistently and correctly) from Day 1 to at least 90 days after the last dose.
* Female participants of childbearing potential must have a negative serum pregnancy test at Screening.
* Male participants with pregnant or nonpregnant women of childbearing potential partners must use a condom.

Exclusion Criteria:

* Severe or unstable CF, per Investigator's judgement.
* Currently being treated for allergic bronchopulmonary aspergillosis or nontuberculous mycobacteria or tuberculosis.
* Active and current infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
* 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.
* Established diagnosis of hepatitis B viral infection or positive for hepatitis B surface antigen (HBsAg) at Screening.
* Established diagnosis of hepatitis C virus (HCV) infection at Screening. Participants positive for hepatitis C antibody are eligible only if HCV RNA is negative.
* History of human immunodeficiency virus (HIV) infection.
* Acute upper or lower respiratory tract infection, pulmonary exacerbation, or changes in therapy (including intravenous and oral antibiotics) for pulmonary disease within 4 weeks prior to Day 1 (administration of the first dose of study drug). Participants meeting this criterion could be rescreened 4 weeks after resolution of symptoms.
* History of prolonged QT/QTc interval with QTcF \>480 millisecond (msec) at Screening.
* History of solid organ or hematological transplantation.
* Have diagnosed periodontal disease and are either:

  1. Currently treated by a dentist for this condition or
  2. Expected to have periodontal disease-related procedures within the study period.
* Received any live attenuated vaccine within 4 weeks prior Screening.
* Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 90 days prior to Screening.
* Known history of hypersensitivity to brensocatib or any of its excipients.
* Use of any immunomodulatory agents within 4 weeks before the Screening Visit is prohibited during the study through end of study (including, but not limited to: bortezomib, ixazomib, thalidomide, cyclophosphamide, mycophenolate, Janus kinase inhibitors, interferon gamma (IFN-γ\], and azathioprine).
* Continuous use of high-dose non-steroidal anti-inflammatory drugs (NSAIDs) is prohibited during the study through end of study.
* History of alcohol, medication, or illicit drug abuse.
* Current smoker, as defined by Centers for Disease Control and Prevention: An adult who has smoked 100 cigarettes in his or her lifetime and who currently smokes cigarettes.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Brensocatib
timeFrame: Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose
measure: Time to Maximum Plasma Concentration (tmax) of Brensocatib
timeFrame: Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose
measure: Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-dose (AUC0-24) of Brensocatib
timeFrame: Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 hours postdose
measure: Elimination Half-life (t1/2) of Brensocatib
timeFrame: Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose
measure: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
timeFrame: Day 1 to Day 56
Secondary outcomes:
measure: Dose-normalized Maximum Plasma Concentration (Cmax) of Brensocatib
timeFrame: Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose
measure: Dose-normalized Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-dose (AUC0-24) of Brensocatib
timeFrame: Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 hours postdose
measure: Dose-normalized Area Under the Concentration-time Curve from Time 0 to the Time of Last Measurable Concentration (AUClast) of Brensocatib
timeFrame: Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: USA001
state: Florida
city: Augusta
country: United States
facility: USA016
state: Georgia
city: Glenview
country: United States
facility: USA025
state: Illinois
city: Boston
country: United States
facility: USA011
state: Massachusetts
city: Ann Arbor
country: United States
facility: USA023
state: Michigan
city: Saint Louis
country: United States
facility: USA002
state: Missouri
city: New York
country: United States
facility: USA022
state: New York
city: Cleveland
country: United States
facility: USA008
state: Ohio
city: Cleveland
country: United States
facility: USA006
state: Ohio
city: Portland
country: United States
facility: USA018
state: Oregon
city: Charleston
country: United States
facility: USA009
state: South Carolina
city: Nashville
country: United States
facility: USA017
state: Tennessee
city: Dallas
country: United States
facility: USA004
state: Texas
city: Tyler
country: United States
facility: USA003
state: Texas
Study officials:
References: