Clearing Lungs With Epithelial Sodium Channel (ENaC) Inhibition in Cystic Fibrosis (CF) (CLEAN-CF)

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of P-1037 Solution for Inhalation in Patients With Cystic Fibrosis (CF)

The goal of the study is to evaluate the safety and tolerability of P-1037 and to determine whether the combination of P-1037 with hypertonic saline or P-1037 alone has a greater effect on lung function in patients with CF than placebo (0.17% saline).

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: P-1037; Drug: Hypertonic Saline; Drug: Saline

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
  • Florida
    • Gainesville, Florida, United States, 32610
      • Univ of Florida Dept of Medicine
    • Miami, Florida, United States, 33136
      • University of Miami Adult CF Center
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group, PA
    • Tampa, Florida, United States, 33606
      • New Lung Associates
  • Illinois
    • Glenview, Illinois, United States, 60025
      • Chicago Cystic Fibrosis Institute
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Harper University Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgets-Robert Wood Johnson Medical School
    • Somerville, New Jersey, United States, 08876
      • Pediatric Pulmonology/Cystic Fibrosis
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • New Hyde Park, New York, United States, 11042
      • Long Island Jewish Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • University of North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Clinical Research of Charlotte
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Santiago Reyes
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Anderson Pharmaceutical Research
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78723
      • Austin Children's Chest Associates
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • San Antonio, Texas, United States, 78212
      • Alamo Clinical Research Associates
    • Tyler, Texas, United States, 75708
      • Univ of Texas Health Science Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Childrens
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin UW Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, 12 years of age or older.
• Diagnosis of cystic fibrosis as determined by the 1997 CF Consensus criteria (NIH Consensus Statement, 1997)
• Non-smoker
• FEV1 at Screening Visit 1 between 40% and 90%
• Stable regimen of CF medications and chest physiotherapy for the 28 days prior to Screening. Must be willing to discontinue use of hypertonic saline for the duration of the study.
• Clinically stable for at least 2 weeks
• All females of child-bearing potential must have a negative serum pregnancy test and if sexually active must agree to practice a highly effective form of contraception throughout the study and for 28 days after the last dose of study medication.

Exclusion Criteria:

• History of any organ transplantation or any significant disease or disorder
• Use of diuretics (including amiloride) or renin-angiotensin antihypertensive drugs or trimethoprim in the 28 days prior to Screening
• History of significant intolerance to inhaled hypertonic saline, as determined by the Investigator
• Known hypersensitivity to the study drug or amiloride

• Any clinically significant laboratory abnormalities at Screening Visit 1 as judged by the investigator, or any of the following:

  • Potassium ≥ 5 milliequivalent per Liter (mEq/L)
  • Abnormal renal function
  • Abnormal liver function, defined as ≥ 3 x upper limit of normal (ULN)
  • Hemoglobin level < 10.0 g/dL
• Female who is pregnant or lactating
• History of sputum or throat swab culture yielding Burkholderia species or Mycobacterium abscessus within 2 years of screening
• Has previously participated in an investigational trial involving administration of any investigational compound or use of an investigational device with 28 days prior to Screening
• Currently being treated with any ivacaftor containing regimen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: P-1037 in Hypertonic Saline (HS); P-1037 Solution for Inhalation, 85 μg twice daily (BID) (28.3 μg/mL) in hypertonic saline (4.2% saline) BID	Drug: P-1037; P-1037 is a novel ENaC inhibitor; Drug: Hypertonic Saline; 4.2% saline solution
Experimental: P-1037 in Saline; P-1037 Solution for Inhalation, 85 μg BID (28.3 μg/mL) in 0.17% saline BID	Drug: P-1037; P-1037 is a novel ENaC inhibitor; Drug: Saline; 0.17% saline solution
Placebo Comparator: Saline; Placebo (0.17% saline) BID	Drug: Saline; 0.17% saline solution
Sham Comparator: Hypertonic Saline; Hypertonic saline (4.2% saline) BID	Drug: Hypertonic Saline; 4.2% saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (number of adverse events of P-1037 in treatment groups)	number of adverse events of P-1037 in treatment groups	Day 15
Safety [change in forced expiratory volume in one second (FEV1) from predosing to 1 hour post dosing]	change in FEV1 from predosing to 1 hour post dosing with P-1037 in 4.2 % hypertonic saline and P-1037 in 0.17% saline	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in FEV1	change in FEV1, from baseline (immediately before first dose) to same time of day on Day 15	Day 15
Effect of P-1037 on other forced vital capacity (FVC) measures (change in FVC from baseline (immediately before first dose) to same time of day on Day 15)	change in FVC from baseline (immediately before first dose) to same time of day on Day 15	Day 15
Effect of P-1037 on Cystic Fibrosis Questionnaire - Revised (CFQ-R)	CFQ-R on Day 15	Day 15
Determine whether co-administration of hypertonic saline (HS) enhances the effect of P-1037 on FEV1 (FEV1 on Day 15)	FEV1 on Day 15	Day 15
Effect of P-1037 on (forced expiratory flow at 25%-75% of vital capacity (FEF25-75%)	FEF25-75% from baseline (immediately before first dose) to same time of day on Day 15	Day 15

Collaborators and Investigators

• Sponsor: Parion Sciences
• Collaborators: Vertex Pharmaceuticals Incorporated
• Investigators: Study Chair: Karl Donn, Parion Sciences

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: January 13, 2015
• First Submitted That Met QC Criteria: January 21, 2015
• First Posted (Estimate): January 22, 2015

Study Record Updates

• Last Update Posted (Actual): July 26, 2021
• Last Update Submitted That Met QC Criteria: July 22, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: PS-G201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided