Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (SNO-2)

This study is currently recruiting participants.
Verified January 2014 by N30 Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
N30 Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01746784
First received: December 6, 2012
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of N6022, and to obtain descriptive information on the effect of N6022 on biomarkers of CFTR function and inflammation in adult cystic fibrosis subjects who are homozygous for the F508del-CFTR mutation.


Condition Intervention Phase
Cystic Fibrosis
Drug: N6022
Drug: Normal saline
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of N6022 to Evaluate Safety and Pharmacokinetics in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (SNO1)

Resource links provided by NLM:


Further study details as provided by N30 Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: Over 7 treatment days and 7 days of follow-up ] [ Designated as safety issue: No ]
    Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.


Secondary Outcome Measures:
  • Change in percent predicted forced expiratory volume in 1 second (FEV1) [ Time Frame: Change from baseline at 7 days ] [ Designated as safety issue: No ]
  • Change in biomarkers of CFTR function [ Time Frame: Change from baseline at 7 days ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change in inflammatory biomarkers [ Time Frame: Change from baseline at 7 days ] [ Designated as safety issue: No ]
    Measured in plasma, induced sputum and stool.

  • Changes in cystic fibrosis respiratory symptom diary version 2 (CFRSD V2) [ Time Frame: Change from baseline at 7 days ] [ Designated as safety issue: No ]
  • Patient global impression of change (PGIC) [ Time Frame: Change from baseline at 7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 67
Study Start Date: February 2014
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: N6022
Subjects randomized to study drug will receive N6022 by intravenous infusion once per day for 7 days
Drug: N6022
Intravenous solution of N6022 in normal saline administered by infusion pump over 1-8 minutes depending on the dose
Other Name: GSNORi
Placebo Comparator: Normal saline
Subjects randomized to placebo will receive normal saline administered intravenously using the same volume as the active drug group
Drug: Normal saline
Intravenous solution of 0.9% (weight/volume) NaCl administered by infusion pump over 1-8 minutes depending on dose of active drug used in same cohort
Other Name: Placebo

Detailed Description:

This is a double-blind, randomized, placebo-controlled, multicenter, sequential dose-escalation study which will occur in two parts. All selection criteria, assessments and procedures described in this protocol will be applied to both parts. Up to 5 cohorts will be studied with a total of 67 patients at approximately 18 clinical sites in the United States.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Homozygous for F508del-CFTR gene
  • Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis
  • Body weight ≥ 40 kg
  • FEV1 ≥ 40% predicted
  • Oxygen saturation ≥ 90% breathing ambient air
  • Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments
  • Negative pregnancy test for women of child bearing potential
  • Sexually active subjects of child bearing potential willing to follow contraception requirements

Exclusion Criteria:

  • Previous enrollment in another cohort for this study.
  • Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment within 4 weeks of Study Day 1.
  • Any change in chronic therapies for CF lung disease within 4 weeks of Study Day 1.
  • Blood hemoglobin <10 g/dL at screening.
  • Serum albumin <2.5 g/dL at screening.
  • Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN) in three or more of the following: AST, ALT, GGT, ALP, total bilirubin at screening.
  • History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year at screening.
  • History, including the screening assessment, of ventricular tachycardia or ventricular arrhythmias.
  • History, including the screening assessment, of prolonged QT and/or QTcF interval (> 450 msec).
  • History of solid organ or hematological transplantation.
  • Intranasal medication changes within 14 days prior to Study Day 1
  • Required Use of continuous (24 hr/d) or nocturnal supplemental oxygen.
  • Concomitant use of any inhibitors or inducers of CYP3A4.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01746784

Contacts
Contact: Steven Shoemaker, MD 720-945-7700 ext 7719 Steven.Shoemaker@N30pharma.com

Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
Contact: Ginger Reeves, RRT    205-638-5970    greeves@peds.uab.edu   
Contact: Heather Hathorne, RRT    205-638-9568    hhathorne@peds.uab.edu   
Principal Investigator: George Solomon, MD         
United States, Alaska
Providence Alaska Medical Center Recruiting
Anchorage, Alaska, United States, 99508
Contact: Vicki Roberts, RN    907-212-3299    Vicki.Roberts@providence.org   
Contact: Kate Nelson, RN    907-212-5615    Kate.Nelson@providence.org   
Principal Investigator: Dion Roberts, MD         
United States, California
Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Colleen Dunn, RN    650-736-0388    cedunn@stanford.edu   
Contact: Zoe Davies       zdavies@stanford.edu   
Principal Investigator: Richard Moss, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Churee Pardee, RN    720-777-6162    churee.pardee@childrenscolorado.org   
Contact: Carol Kopecky, RN    720-777-5416    carol.kopecky@childrenscolorado.org   
Principal Investigator: Edith Zemanick, MD         
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Contact: Marion Jones, RN BSN    303-398-1265    jonesm@njhealth.org   
Contact: Connie St. Clair, RN BSN MS    303-270-2517    stclairc@njhealth.org   
Principal Investigator: Jennifer Taylor-Cousar, MD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Raquel Garcia-Cano, RN    312-695-0415    raquel.garcia-cano@northwestern.edu   
Contact: Clare Marlin    312-695-2269    clare-murphy@northwestern.edu   
Principal Investigator: Manu Jain, MD         
United States, Iowa
University of Iowa Children's Hospital Recruiting
Iowa City, Iowa, United States, 52242
Contact: Mary Teresi, PharmD    319-384-7546    mary-teresi@uiowa.edu   
Contact: Angela Majeskie    319-384-4669    angela-majeskie@uiowa.edu   
Principal Investigator: Richard Ahrens, MD         
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Karen Callahan, RN    410-955-1167    kcallah1@jhmi.edu   
Principal Investigator: Pamela Zeitlin, MD, PhD         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jonathan Greenberg    617-355-6665    Jonathan.Greenberg@childrens.harvard.edu   
Contact: Robert Fowler    617-355-1834    Robert.fowler@childrens.harvard.edu   
Principal Investigator: Alicia Casey, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Patricia Grover    612-626-7425    Grove026@umn.edu   
Contact: Denise Stacklie    612-626-9491    stack046@umn.edu   
Principal Investigator: Joanne Billings, MD         
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Patty Burks, RN CCRA    314-454-5175    Burks_p@kids.wustl.edu   
Contact: Denise Rodgers    314-286-1176    rodgers@kids.wustl.edu   
Principal Investigator: Daniel Rosenbluth, MD         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Nadia Bendahmane-Shive, RC    919-966-9198    nadia_bendahmane@med.unc.edu   
Contact: Claudia Salazar, RC    (919) 966-9198    Claudia_salazar@med.unc.edu   
Principal Investigator: Scott Donaldson, MD         
United States, Ohio
Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Beth Decker, RN    513-803-4325    Beth.decker@cchmc.org   
Contact: Delana Terrill, RRT    513-636-9780    Delana.terril@cchmc.org   
Principal Investigator: John P Clancy, MD         
Rainbow Babies and Children's Hospital - Case Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Bobbi Ksenich, RN CCRC    216-844-5733    Roberta.Ksenich@UHHospitals.org   
Contact: Dave Weaver    216-983-0469    David.Weaver@uhhospitals.org   
Principal Investigator: James Chmiel, MD         
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Terri Johnson, RN BSN    614-722-4766    Terri.Johnson@nationwidechildrens.org   
Contact: Patty Olson, RC    614-722-4766    patti.olson@nationwidechildrens.org   
Principal Investigator: Karen McCoy, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Erin Donnelly, RN    267-426-9626    Donnellye4@email.chop.edu   
Contact: Christina Kubrak    267-426-5135    Kubrak@email.chop.edu   
Principal Investigator: Ron Rubenstein, MD         
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Adrienne DeRicco, RN    412-692-8069    Adrienne.dericco@chp.edu   
Contact: Elizabeth Hartigan    412-692-7060    Elizabeth.hartigan@chp.edu   
Principal Investigator: Joseph Pilewski, MD         
Sponsors and Collaborators
N30 Pharmaceuticals, Inc.
Investigators
Principal Investigator: Scott Donaldson, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
No publications provided

Responsible Party: N30 Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01746784     History of Changes
Other Study ID Numbers: N6022-1CF1-04
Study First Received: December 6, 2012
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by N30 Pharmaceuticals, Inc.:
Cystic Fibrosis
F508del-CFTR
N6022
S-Nitrosoglutathione

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 15, 2014