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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00434278
• Collaborator: (none)
• Enrollment: 27
• Locations: 40
• Arms: 2
• Duration (Months): 20.1
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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 Patients were randomized to either continue Pulmozyme or have therapy withdrawn for 2 weeks (placebo group).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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Dornase alfa; Drug: placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Distance Walked in the 6-minute Walk Test [From baseline to Day 14]

   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.

Secondary Outcome Measures

1. Change in Pulmonary Function as Measured by FEV1 and FVC [From baseline to Day 14]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Genentech, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT00434278
• Other Study ID Numbers: Z3877g
• First Posted: Feb 13, 2007
• Last Update Posted: May 16, 2017
• Last Verified: May 1, 2017

• Keywords provided by Genentech, Inc.: Lung disease; CF; Pulmozyme
• Additional relevant MeSH terms: Cystic Fibrosis; Lung Diseases; Fibrosis

Study Results

Participant Flow

Arm/Group Title	Placebo	Dornase Alfa
Arm/Group Description	2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)	2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)
Period Title: Overall Study
STARTED	14	13
COMPLETED	12	13
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Placebo	Dornase Alfa	Total
Arm/Group Description	2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)	2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)	Total of all reporting groups
Overall Participants	14	13	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.6 (7.0)	29.8 (10.0)	27.1 (8.8)
Sex: Female, Male (Count of Participants)
Female	4 28.6%	3 23.1%	7 25.9%
Male	10 71.4%	10 76.9%	20 74.1%

Outcome Measures

1. Primary Outcome

Title	Change in Distance Walked in the 6-minute Walk Test
Description	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.
Time Frame	From baseline to Day 14

Outcome Measure Data

Analysis Population Description

Randomized patients. For placebo arm: 2 placebo patients who were randomized did not complete the study and therefore had no values to calculate change from baseline computation.

Arm/Group Title	Placebo	Dornase Alfa
Arm/Group Description	2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)	2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)
Measure Participants	12	13
Mean (Standard Deviation) [Meters]	25.2 (79.8)	26.9 (60.0)

2. Secondary Outcome

Title	Change in Pulmonary Function as Measured by FEV1 and FVC
Description	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.
Time Frame	From baseline to Day 14

Outcome Measure Data

Analysis Population Description

Randomized patients. Patients not included in this analysis did not meet ATS reproducibility criteria. Two patients in the placebo arm whose screening visit values did not meet ATS reproducibility criteria were randomized in error and completed the study.

Arm/Group Title	Placebo	Dornase Alfa
Arm/Group Description	2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)	2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)
Measure Participants	11	12
FEV1	-0.5 (4.1)	0.2 (2.8)
FVC	-1.2 (4.5)	1.0 (4.8)

Adverse Events

Adverse Event Reporting Description	Randomized (same as safety-evaluable) patients. Note: The incidence of each AE/SAE is reported as the number of participants experiencing the event, not the number of occurrences for each AE/SAE.
Arm/Group Title	Placebo		Dornase Alfa
Arm/Group Description	2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)		2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3)
All Cause Mortality
	Placebo		Dornase Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Dornase Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)		2/13 (15.4%)
Congenital, familial and genetic disorders
Cystic Fibrosis	1/14 (7.1%)		1/13 (7.7%)
Cystic Fibrosis Lung	1/14 (7.1%)		0/13 (0%)
Gastrointestinal disorders
Distal Intestinal Obstruction Syndrome	0/14 (0%)		1/13 (7.7%)
Other (Not Including Serious) Adverse Events
	Placebo		Dornase Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)		4/13 (30.8%)
Congenital, familial and genetic disorders
Cystic Fibrosis	0/14 (0%)		1/13 (7.7%)
General disorders
Fatigue	0/14 (0%)		1/13 (7.7%)
Chest Discomfort	1/14 (7.1%)		0/13 (0%)
Non-Cardiac Chest Pain	1/14 (7.1%)		0/13 (0%)
Metabolism and nutrition disorders
Decreased Appetite	0/14 (0%)		1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Muscle Spasms	1/14 (7.1%)		0/13 (0%)
Nervous system disorders
Headache	1/14 (7.1%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/14 (7.1%)		0/13 (0%)
Cough	1/14 (7.1%)		0/13 (0%)
Haemoptysis	1/14 (7.1%)		0/13 (0%)
Productive Cough	0/14 (0%)		1/13 (7.7%)
Rhinitis Allergic	0/14 (0%)		1/13 (7.7%)
Respiratory Tract Congestion	0/14 (0%)		1/13 (7.7%)

Limitations/Caveats

Because the study was terminated (for administrative reasons and infeasibility of enrollment), no conclusions can be made about the effect of Pulmozyme on exercise tolerance in this population.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.