A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Brensocatib Tablets in Adults With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05090904
• Other study ID #: INS1007-211
• Status: Completed
• Phase: Phase 2
• Start date: November 30, 2021
• Est. completion date: November 1, 2022

Study information

• Verified date: October 2023
• Source: Insmed Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: November 1, 2022
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-?], 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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Brensocatib
Oral tablet
• Placebo
Oral tablet

Locations

Country	Name	City	State
United States	USA023	Ann Arbor	Michigan
United States	USA016	Augusta	Georgia
United States	USA011	Boston	Massachusetts
United States	USA009	Charleston	South Carolina
United States	USA006	Cleveland	Ohio
United States	USA008	Cleveland	Ohio
United States	USA004	Dallas	Texas
United States	USA001	Gainesville	Florida
United States	USA025	Glenview	Illinois
United States	USA017	Nashville	Tennessee
United States	USA022	New York	New York
United States	USA018	Portland	Oregon
United States	USA002	Saint Louis	Missouri
United States	USA003	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Insmed Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax) of Brensocatib		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
Primary	Time to Maximum Plasma Concentration (tmax) of Brensocatib		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
Primary	Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-dose (AUC0-24) of Brensocatib		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
Primary	Elimination Half-life (t1/2) of Brensocatib		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
Primary	Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)		Day 1 to Day 56
Secondary	Dose-normalized Maximum Plasma Concentration (Cmax) of Brensocatib		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
Secondary	Dose-normalized Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-dose (AUC0-24) of Brensocatib		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
Secondary	Dose-normalized Area Under the Concentration-time Curve from Time 0 to the Time of Last Measurable Concentration (AUClast) of Brensocatib		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