Study of N91115 in Patients With Cystic Fibrosis Homozygous F508del-CFTR Mutation
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Interventional
Phase: Phase 1

Summary: 
      This Phase 1b study in F508del-CFTR homozygous CF patients is being conducted to assess the
      safety of N91115 as the sole cystic fibrosis transmembrane conductance regulator (CFTR)
      modulator at doses near the expected therapeutic exposure level in preparation for Phase 2
      studies of N91115 added to the CFTR modulator combination lumacaftor/ivacaftor when launched.
    

Detailed description: 
      Study procedures, frequency and timing are provided in the attached study schema. Adverse
      events and concomitant medication will be monitored throughout the study from informed
      consent signing until end of study participation. A Data Monitoring Committee (DMC) will also
      review unblinded safety data on a monthly basis throughout the study. Limitations on
      bronchodilators for pulmonary assessments prior to study drug dosing are described below
      except in emergent situations.

        -  Short acting β-agonists and anticholinergics will be held for at least 4 hours

        -  Long acting β-agonists dosed twice daily will be held for at least 12 hours

        -  Long acting β-agonists dosed once daily and long acting anticholinergics will be held
           for at least 24 hours

      Screening (Day -28 to Day -3):

      Patients will sign the informed consent and undergo procedures to determine eligibility
      including pregnancy testing, demographic information, medical history, and genotype by
      historical confirmation or blood sample confirmation (as applicable), height and weight,
      12-Lead electrocardiogram (ECG), 48-hour Holter monitoring, chemistry, hematology, full
      physical examination, sweat chloride, smoking and alcohol history, spirometry, sputum
      microbiology, urinalysis and vital signs.

      Day 1 Predose (Day -2 to -1) Patients will return to the clinic to reconfirm eligibility and
      assess any changes in medical history and pregnancy status. An abbreviated physical
      examination focusing on cardiovascular, pulmonary and gastrointestinal systems plus an
      assessment of weight will be conducted. The following will be obtained: 12-lead ECG,
      abbreviated physical exam, blood for DNA (optional), blood for leukocyte messenger
      ribonucleic acid (mRNA), blood inflammatory biomarkers, cystic fibrosis questionnaire-revised
      (CFQ-R), O2 Sat, patient global impression of change (PGIC), safety labs, serum
      pharmacokinetics (PK), spirometry, sputum microbiology, sweat chloride (SC) (if more than 2
      weeks since the screening value was obtained), and vital signs. Sites may choose to perform
      any of these assessments on Day -2, Day -1 or Day 1 predose except for serum PK that starts
      Day 1 predose and vital signs that are done Day 1 predose.

      Dosing and Food Intake:

      Patients will take their dose of study drug every 12 hours at approximately the same time
      each morning and night. There are no restrictions related to food intake.

      Dosing Days 1 and 2:

      On Day 1, patients will be observed for at least 4 hours following the first dose of study
      drug. Patients return to the clinical site on Day 2 for a predose PK sample that is 24 hours
      after their first dose. Patients will be observed for at least 2 hours after the second dose
      on Day 2.

      Days 3-28:

      Patients self-administer study drug at approximately the same time each morning and evening
      with the exception that the morning doses on clinic Days 7, 14, 21 and 28, which will be
      administered and witnessed in the clinic.

      Day 7 (Dosing in Clinic):

      On Day 7, patients will return to the clinic to monitor any changes in health status and for
      an abbreviated physical exam, 12-Lead ECG, O2 Sat, safety labs, PK, spirometry, study drug
      compliance, SC and vital signs.

      Day 14 (Dosing in Clinic):

      On Day 14, patients will return to the clinic to monitor any changes in health status and for
      an abbreviated physical exam, urine pregnancy, 12-lead ECG, blood inflammatory biomarkers,
      CFQ-R, O2 Sat, safety labs, PK, spirometry, study drug compliance, SC and vital signs.

      Day 21 (Dosing in Clinic):

      On Day 21, patients will return to the clinic to monitor any changes in health status and for
      an abbreviated physical exam, 12-Lead ECG, O2 Sat, safety labs, PK, spirometry, study drug
      compliance, SC and vital signs.

      Day 28 (Dosing in Clinic):

      On Day 28 patients will return to the clinic to monitor any changes in health status and for
      an abbreviated physical exam, 12-Lead ECG, blood for DNA (optional), blood for leukocyte
      mRNA, blood inflammatory biomarkers, CFQ-R, urine pregnancy, O2 Sat, PGIC, safety labs, PK,
      spirometry, sputum microbiology, study drug compliance, SC, weight, and vital signs.

      Day 42 (Final study day 2 weeks after last dose):

      On Day 42 (± 2 days) study follow-up assessments include: abbreviated physical exam, blood
      inflammatory biomarkers, O2 Sat, PGIC, spirometry, SC, weight, and vital signs.
    

Intervention name(s): N91115
Intervention type(s): Drug
Intervention description(s): S Nitrosoglutathione Reductase Inhibitor
Other intervention name(s): Cavosonstat
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: N91115; Cavosonstat