A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease

This was a multicenter, randomized, double-blind, placebo-controlled study of patients with severe, though stable, cystic fibrosis (CF) whose routine treatment included Pulmozyme. Patients were randomized to either continue Pulmozyme or have therapy withdrawn for 2 weeks (placebo group). Patients must have had stable CF symptoms without any change in therapy for 2 weeks prior to enrollment in order to participate.

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: placebo; Drug: Dornase alfa

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • California
    • Los Angeles, California, United States, 90027
      • Childrens Hospital of LA
    • Los Angeles, California, United States, 90033
      • USC Adult CF Center
    • Orange, California, United States, 92868
      • CHOC
    • Sacramento, California, United States, 95819
      • Capital Allergy Resp Dis Ctr
    • Ventura, California, United States, 93003
      • Ventura County Medical Ctr
  • Colorado
    • Denver, Colorado, United States, 80206
      • Nat'l Jewish Med/Research Ctr
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Pulm & Critical Care Assoc
    • Miami, Florida, United States, 33136
      • Univ of Miami
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Grou
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Brown Univ School of Medicine
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Univ of Kentucky Med Ctr
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5212
      • Univ of Michigan Hlth System
    • Detroit, Michigan, United States, 48201
      • Wayne State University
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Hospital
    • Kalamazoo, Michigan, United States, 49008
      • Michigan State University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Univ of Minnesota Dept of Derm
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Pulmonary & Critical Care Med
  • Nevada
    • Las Vegas, Nevada, United States, 89107
      • Children's Lung Specialist
  • New Jersey
    • Long Branch, New Jersey, United States, 07740
      • Monmouth Medical Center
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital
    • New Brunswick, New Jersey, United States, 08901
      • St. Peters Univ Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • University of New Mexico
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • New Hyde Park, New York, United States, 11040
      • Long Island Jew Adult CF Ctr
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical Univ
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Pediatric Clinical
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies & Child Hosp
    • Toledo, Ohio, United States, 43606
      • Toledo Childrens Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Santiago Reyes MD-Private Prac
    • Tulsa, Oklahoma, United States, 74145
      • CF Solutions, Inc
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical Univ of South Carolina
    • Columbia, South Carolina, United States, 29203
      • Pediatric Pulmonary Assoc
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78212
      • Alamo Clinical Research Assoc
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • W Virginia Univ Health Sci Ctr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed Informed Consent Form and, if applicable, Assent Form
• Age ≥ 14 years old at screening
• Proven diagnosis of CF
• Ability to perform acceptable and reproducible spirometry maneuvers at screening
• FVC ≤ 45% predicted for race, height, age, and sex at screening
• Chronic use of Pulmozyme for at least 3 months in the last year and daily or twice daily use during the 14 days prior to screening
• Stable regimen of chest physiotherapy (CPT) for at least 14 days prior to screening
• Ability to complete the 6-minute walk test at screening
• Ability to complete the 6-minute walk test and spirometry at Visit 2
• If on routine tobramycin solution for inhalation (i.e., TOBI®) or other cycled antibiotic therapy, intention to either start or stop therapy at the time of Visit 2 (based on routine therapy cycle; no other planned change in this antibiotic regimen for 28 days before or 28 days after Visit 2)
• Clinically stable with no change in medications during the 14 days prior to screening

Exclusion Criteria:

• Use of an investigational drug or device within 28 days prior to screening
• Previous episode of acute respiratory failure requiring assisted ventilation within 2 years prior to screening
• Previous lung transplant
• Any cardiac disease that would contraindicate performing the 6-minute walk test
• Pregnancy or nursing
• Known hypersensitivity or other contraindication to the use of Pulmozyme
• Previous completion or premature discontinuation of study drug or withdrawal from this study
• More than one prior screening failure for this study at any time or any prior screening failure for this study within the last 28 days

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; 2.5 mg inhalation dose twice daily for 14±2 days
Experimental: Dornase alfa	Drug: Dornase alfa; 2.5 mg inhalation dose twice daily for 14±2 days; Other Names: Pulmozyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Distance Walked in the 6-minute Walk Test	Change in distance walked was defined as (distance walked in 6 minutes at baseline [Day 0]) - (distance walked in 6 minutes at Day 14) in meters.	From baseline to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pulmonary Function as Measured by FEV1 and FVC	FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) were recorded at Day 0 (baseline) and Day 14. Change in FEV1 and FVC from baseline to Day 14 was reported as a percentage of values predicted for age, height, and race.	From baseline to Day 14

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Michelle Freemer, M.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: February 11, 2007
• First Submitted That Met QC Criteria: February 11, 2007
• First Posted (Estimate): February 13, 2007

Study Record Updates

• Last Update Posted (Actual): May 16, 2017
• Last Update Submitted That Met QC Criteria: May 12, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: CF; Pulmozyme; Lung disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Lung Diseases; Cystic Fibrosis
• Other Study ID Numbers: Z3877g