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Study of N91115 in Patients With Cystic Fibrosis Homozygous F508del-CFTR Mutation (SNO4)

3. november 2016 opdateret af: Nivalis Therapeutics, Inc.

A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Parallel, Group Study of N91115 to Evaluate Safety and Pharmacokinetics in Patients With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

51

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Alabama
      • Birmingham, Alabama, Forenede Stater, 35294
        • University of Alabama @ Birmingham
    • California
      • Palo Alto, California, Forenede Stater, 94304
        • Stanford University
    • Colorado
      • Aurora, Colorado, Forenede Stater, 80045
        • Children's CO
      • Denver, Colorado, Forenede Stater, 80206
        • National Jewish Health
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60611
        • Northwestern University
    • Indiana
      • Indianapolis, Indiana, Forenede Stater, 46202
        • Indiana University
    • Iowa
      • Iowa City, Iowa, Forenede Stater, 52242
        • University of Iowa Children's Hospital
    • Maryland
      • Baltimore, Maryland, Forenede Stater, 21287
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02115
        • Boston Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, Forenede Stater, 55455
        • University of Minnesota
    • Missouri
      • St. Louis, Missouri, Forenede Stater, 63110
        • Washington University
    • New York
      • New York, New York, Forenede Stater, 10032
        • Columbia University
      • New York, New York, Forenede Stater, 10032
        • The New York Presbyterian Hospital, Columbia University Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, Forenede Stater, 27599
        • University of North Carolina
    • Ohio
      • Cincinnati, Ohio, Forenede Stater, 45229
        • Cincinnati Children's Hospital
      • Cleveland, Ohio, Forenede Stater, 44106
        • Rainbow Babies and Children's Hospital - Case Medical Center
      • Columbus, Ohio, Forenede Stater, 43205
        • Nationwide Children's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19104
        • Children's Hospital of Philadelphia
    • Washington
      • Seattle, Washington, Forenede Stater, 98105
        • Seattle Children's Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 80 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  1. Male or female, age ≥ 18 years with confirmed diagnosis of CF, homozygous for the F508del-CFTR mutation based on historical results generated by Ambry Genetics within the past two years or if unavailable, confirmed by testing done within the past 28 days
  2. Sweat chloride ≥ 60 (milliequivalents) mEq/L, by quantitative pilocarpine iontophoresis test (QPIT) at screening
  3. Weight ≥ 40 kg at screening
  4. Forced expiratory volume (FEV1) ≥ 40% of predicted normal for age, gender, and height (Hankinson standards) pre- or post-bronchodilator value, at screening
  5. Oxygen saturation by pulse oximetry ≥ 90% breathing ambient air, at screening
  6. Hematology, clinical chemistry and urinalysis results with no clinically significant abnormalities that would interfere with the study assessments at screening

Exclusion Criteria:

  1. Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment or hospitalization within 2 weeks of Study Day 1
  2. Any change in chronic therapies for CF lung disease (e.g., Ibuprofen, Pulmozyme®, hypertonic saline, Azithromycin, Tobi®, Cayston®) within 4 weeks of Study Day 1
  3. Blood hemoglobin < 10 g/dL at screening
  4. Serum albumin < 2.5 g/dL at screening
  5. Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN) in 3 or more of the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT), g-glutamyl transferase (GGT), alkaline phosphatase (ALP), or total bilirubin at screening
  6. History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year of screening
  7. History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias
  8. History, including the screening assessment, of prolonged cardiac QT interval and/or QTcF (QT with Fridericia's correction) interval (> 450 msec)
  9. History of solid organ or hematological transplantation
  10. History of alcohol abuse or drug abuse (including cannabis, cocaine, and opioids) in the year prior to screening
  11. Use of continuous (24 hr/day) or nocturnal supplemental oxygen

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Group 1 - 50 mg
Every 12 hour oral dosing of N91115 for 28 days
Medicin: N91115
S Nitrosoglutathione Reductase Inhibitor
Andre navne:
  • Cavosonstat
Eksperimentel: Group 2 - 100 mg
Every 12 hour oral dosing of N91115 for 28 days
Medicin: N91115
S Nitrosoglutathione Reductase Inhibitor
Andre navne:
  • Cavosonstat
Eksperimentel: Group 3 - 200 mg
Every 12 hour oral dosing of N91115 for 28 days
Medicin: N91115
S Nitrosoglutathione Reductase Inhibitor
Andre navne:
  • Cavosonstat
Placebo komparator: Group 4 - Placebo
Every 12 hour oral dosing of placebo comparator for 28 days
Medicin: N91115
S Nitrosoglutathione Reductase Inhibitor
Andre navne:
  • Cavosonstat

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Safety assessments based on clinical evaluations, laboratory assessments, and adverse events.
Tidsramme: 28 Days
28 Days

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
Tidsramme: 28 Days
Area under the curve(AUC) assessments
28 Days
Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
Tidsramme: 28 Days
Maximum plasma concentration (Cmax) determinations
28 Days
Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
Tidsramme: 28 Days
Ratio of parent:glucuronide metabolite
28 Days

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Nivalis Therapeutics, Inc.

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. februar 2015

Primær færdiggørelse (Faktiske)

1. juli 2015

Studieafslutning (Faktiske)

1. juli 2015

Datoer for studieregistrering

Først indsendt

14. oktober 2014

Først indsendt, der opfyldte QC-kriterier

23. oktober 2014

Først opslået (Skøn)

27. oktober 2014

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

6. november 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

3. november 2016

Sidst verificeret

1. november 2016

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • N91115-1CF-03

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Cystisk fibrose

Kliniske forsøg med N91115

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Ethiopia

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner