Trial Outcomes & Findings for Scleroderma Lung Disease (NCT NCT00004563)

NCT ID: NCT00004563

Last Updated: 2015-03-27

Results Overview

The primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 158 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2015-03-27

Participant Flow

Participant milestones

Measure	Cylophosphamide Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram. Cyclophosphamide: Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.	Placebo Matching gel caps at a dose of 25 mg Placebo: Matching gelcaps 25 mgs
Overall Study STARTED	79	79
Overall Study COMPLETED	54	55
Overall Study NOT COMPLETED	25	24

Reasons for withdrawal

Measure	Cylophosphamide Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram. Cyclophosphamide: Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.	Placebo Matching gel caps at a dose of 25 mg Placebo: Matching gelcaps 25 mgs
Overall Study Withdrawal by Subject	20	16
Overall Study Lack of Efficacy	3	5
Overall Study Death	2	3

Baseline Characteristics

Scleroderma Lung Disease

Baseline characteristics by cohort

Measure	Cylophosphamide n=79 Participants Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram. Cyclophosphamide: Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.	Placebo n=79 Participants Matching gel caps at a dose of 25 mg Placebo: Matching gelcaps 25 mgs	Total n=158 Participants Total of all reporting groups
Age, Continuous	48.2 Years STANDARD_DEVIATION 1.4 • n=5 Participants	47.5 Years STANDARD_DEVIATION 1.4 • n=7 Participants	47.9 Years STANDARD_DEVIATION 1 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	51 Participants n=7 Participants	111 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	28 Participants n=7 Participants	47 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: The Number of Participants Analyzed is not consistent with the Participant Flow for the following reason: a number of the patients who withdrew, had treatment failure, or died had completed at least the six-month visit--for these patients, a generalized estimating-equation regression model was fitted, and data missing at 12 months were imputed.

The primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC.

Outcome measures

Measure	Cylophosphamide n=73 Participants Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram. Cyclophosphamide: Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.	Placebo n=72 Participants Matching gel caps at a dose of 25 mg Placebo: Matching gelcaps 25 mgs
Forced Vital Capacity	66.6 % of predicted Standard Error 1.7	65.6 % of predicted Standard Error 1.6

SECONDARY outcome

Timeframe: 12 months

Population: The Number of Participants Analyzed is not consistent with the Participant Flow for the following reason: a number of the patients who withdrew, had treatment failure, or died had completed at least the six-month visit--for these patients, a generalized estimating-equation regression model was fitted, and data missing at 12 months were imputed.

expressed as a percentage of the predicted value

Outcome measures

Measure	Cylophosphamide n=73 Participants Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram. Cyclophosphamide: Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.	Placebo n=72 Participants Matching gel caps at a dose of 25 mg Placebo: Matching gelcaps 25 mgs
Total Lung Capacity	70.5 % of predicted Standard Error 1.8	64.7 % of predicted Standard Error 1.9

SECONDARY outcome

Timeframe: 12 months

Population: The Number of Participants Analyzed is not consistent with the Participant Flow for the following reason: a number of the patients who withdrew, had treatment failure, or died had completed at least the six-month visit--for these patients, a generalized estimating-equation regression model was fitted, and data missing at 12 months were imputed.

diffusing capacity of the lungs for carbon monoxide

Outcome measures

Measure	Cylophosphamide n=73 Participants Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram. Cyclophosphamide: Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.	Placebo n=72 Participants Matching gel caps at a dose of 25 mg Placebo: Matching gelcaps 25 mgs
DLCO	42.8 % of predicted Standard Error 1.7	44.3 % of predicted Standard Error 2.1

Adverse Events

Cylophosphamide

Serious events: 5 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cylophosphamide n=79 participants at risk Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram. Cyclophosphamide: Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.	Placebo n=79 participants at risk Matching gel caps at a dose of 25 mg Placebo: Matching gelcaps 25 mgs
Blood and lymphatic system disorders Leukopenia with pneumonia	1.3% 1/79 • Number of events 1 • 12 months	0.00% 0/79 • 12 months
Blood and lymphatic system disorders Leukopenia with gastroenteritis	1.3% 1/79 • Number of events 1 • 12 months	0.00% 0/79 • 12 months
General disorders Death	2.5% 2/79 • Number of events 2 • 12 months	3.8% 3/79 • Number of events 3 • 12 months
Renal and urinary disorders Pneumonia and Laryngospasm	3.8% 3/79 • Number of events 3 • 12 months	0.00% 0/79 • 12 months
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/79 • 12 months	2.5% 2/79 • Number of events 2 • 12 months

Other adverse events

Measure	Cylophosphamide n=79 participants at risk Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram. Cyclophosphamide: Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.	Placebo n=79 participants at risk Matching gel caps at a dose of 25 mg Placebo: Matching gelcaps 25 mgs
Blood and lymphatic system disorders Neutropenia	8.9% 7/79 • Number of events 7 • 12 months	0.00% 0/79 • 12 months
Respiratory, thoracic and mediastinal disorders Pneumonia	6.3% 5/79 • Number of events 5 • 12 months	1.3% 1/79 • Number of events 1 • 12 months
Renal and urinary disorders Hematuria	11.4% 9/79 • Number of events 9 • 12 months	3.8% 3/79 • Number of events 3 • 12 months
Blood and lymphatic system disorders Leukopenia	24.1% 19/79 • Number of events 19 • 12 months	0.00% 0/79 • 12 months

Additional Information

Maureen Mayes, MD

University of Texas Health Science Center at Houston

Phone: +1 (713) 500-6900

Email: Maureen.D.Mayes@uth.tmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place