Trial Outcomes & Findings for Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II) (NCT NCT00883129)

Last Updated: 2017-02-10

Results Overview

The primary outcome is the course over time from baseline to 24 months for the FVC %-predicted. The FVC %-predicted represents the adjusted volume of air (adjusted as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity) that can be forcibly exhaled from the lungs after taking the deepest breath possible. The FVC %-predicted is reduced in patients with interstitial lung disease and is used as a measure of lung involvement and disease severity.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

142 participants

Primary outcome timeframe

Measured at study Baseline and Months 3, 6, 12, 15, 18, 21, and 24

Results posted on

2017-02-10

Participant Flow

Recruitment was carried out between September 28, 2009, and January 14, 2013, at 14 University Medical Centers within the United States.

Participant milestones

Participant milestones
Measure	Mycophenolate Arm Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Overall Study STARTED	69	73
Overall Study COMPLETED	49	37
Overall Study NOT COMPLETED	20	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Mycophenolate Arm Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Overall Study Adverse Event	7	15
Overall Study Withdrawal by Subject	8	9
Overall Study Non-compliance	3	6
Overall Study Lost to Follow-up	1	2
Overall Study Death	1	2
Overall Study Defined Treatment Failure	0	2

Baseline Characteristics

Only participants with available data included

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mycophenolate Arm n=69 Participants Participants will receive oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants will receive oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.	Total n=142 Participants Total of all reporting groups
SF-36 Physical component	36.0 Score STANDARD_DEVIATION 10.0 • n=69 Participants	35.6 Score STANDARD_DEVIATION 9.8 • n=73 Participants	35.8 Score STANDARD_DEVIATION 9.9 • n=142 Participants
Age, Continuous	52.6 years STANDARD_DEVIATION 9.7 • n=69 Participants	52.0 years STANDARD_DEVIATION 9.8 • n=73 Participants	52.3 years STANDARD_DEVIATION 9.7 • n=142 Participants
Sex: Female, Male Female	48 Participants n=69 Participants	57 Participants n=73 Participants	105 Participants n=142 Participants
Sex: Female, Male Male	21 Participants n=69 Participants	16 Participants n=73 Participants	37 Participants n=142 Participants
Duration of scleroderma	2.6 years STANDARD_DEVIATION 1.7 • n=67 Participants • Only participants with available data included	2.5 years STANDARD_DEVIATION 1.8 • n=72 Participants • Only participants with available data included	2.6 years STANDARD_DEVIATION 1.8 • n=139 Participants • Only participants with available data included
Limited cutaneous scleroderma	26 Participants n=69 Participants	33 Participants n=73 Participants	59 Participants n=142 Participants
Diffuse cutaneous scleroderma	43 Participants n=69 Participants	40 Participants n=73 Participants	83 Participants n=142 Participants
modified-Rodnan Skin Score	15.3 Score STANDARD_DEVIATION 10.4 • n=69 Participants	14.0 Score STANDARD_DEVIATION 10.6 • n=73 Participants	14.7 Score STANDARD_DEVIATION 10.5 • n=142 Participants
FVC %-predicted	66.5 Percent of predicted normal value STANDARD_DEVIATION 9.1 • n=69 Participants	66.5 Percent of predicted normal value STANDARD_DEVIATION 8.3 • n=73 Participants	66.5 Percent of predicted normal value STANDARD_DEVIATION 9.9 • n=142 Participants
FEV1/FVC %-predicted	81.0 Percent of predicted normal value STANDARD_DEVIATION 5.5 • n=69 Participants	83.3 Percent of predicted normal value STANDARD_DEVIATION 5.6 • n=73 Participants	82.6 Percent of predicted normal value STANDARD_DEVIATION 5.6 • n=142 Participants
Total Lung Capacity	66.3 Percent of predicted normal value STANDARD_DEVIATION 10.0 • n=69 Participants	65.5 Percent of predicted normal value STANDARD_DEVIATION 12.0 • n=73 Participants	65.8 Percent of predicted normal value STANDARD_DEVIATION 11.1 • n=142 Participants
Single-Breath Diffusing Capacity	60.9 Percent of predicted normal value STANDARD_DEVIATION 11.8 • n=69 Participants	61.0 Percent of predicted normal value STANDARD_DEVIATION 13.7 • n=73 Participants	60.9 Percent of predicted normal value STANDARD_DEVIATION 12.8 • n=142 Participants
Mahler Dyspnea Index, mean focal score	7.3 Score STANDARD_DEVIATION 2.1 • n=65 Participants • Only participants with available data included	7.1 Score STANDARD_DEVIATION 2.3 • n=68 Participants • Only participants with available data included	7.2 Score STANDARD_DEVIATION 2.2 • n=133 Participants • Only participants with available data included
SF-36 Mental component	49.1 Score STANDARD_DEVIATION 7.9 • n=69 Participants	49.8 Score STANDARD_DEVIATION 10.0 • n=73 Participants	49.4 Score STANDARD_DEVIATION 9.0 • n=142 Participants
HAQ disability index	0.7 Score STANDARD_DEVIATION 0.6 • n=69 Participants	0.7 Score STANDARD_DEVIATION 0.7 • n=73 Participants	0.7 Score STANDARD_DEVIATION 0.7 • n=142 Participants
Quantitative extent of lung fibrosis on HRCT, for whole lung	8.3 Score STANDARD_DEVIATION 6.9 • n=66 Participants • Only participants with available data included	8.9 Score STANDARD_DEVIATION 7.0 • n=71 Participants • Only participants with available data included	8.6 Score STANDARD_DEVIATION 6.9 • n=137 Participants • Only participants with available data included
Quantitative extent of lung fibrosis on HRCT, for lobe of maximum involvement	23.0 Score STANDARD_DEVIATION 20.2 • n=66 Participants • Only participants with available data included	22.6 Score STANDARD_DEVIATION 19.3 • n=71 Participants • Only participants with available data included	22.8 Score STANDARD_DEVIATION 19.6 • n=137 Participants • Only participants with available data included
Quantitative extent of total insterstitial lung disease on HRCT, for whole lung	27.2 Score STANDARD_DEVIATION 13.2 • n=66 Participants • Only participants with available data included	31.6 Score STANDARD_DEVIATION 14.4 • n=71 Participants • Only participants with available data included	29.5 Score STANDARD_DEVIATION 14.0 • n=137 Participants • Only participants with available data included
Quantitative extent of total insterstitial lung disease on HRCT, for lobe of maximum involvement	50.0 Score STANDARD_DEVIATION 20.9 • n=66 Participants • Only participants with available data included	52.3 Score STANDARD_DEVIATION 19.9 • n=71 Participants • Only participants with available data included	51.2 Score STANDARD_DEVIATION 20.3 • n=137 Participants • Only participants with available data included
ANA(+)	61 Participants n=63 Participants • Only participants with available data included	66 Participants n=71 Participants • Only participants with available data included	127 Participants n=134 Participants • Only participants with available data included
Topoisomerase-1(+)	29 Participants n=63 Participants • Only participants with available data included	32 Participants n=71 Participants • Only participants with available data included	61 Participants n=134 Participants • Only participants with available data included
RNA Polymerase(+)	9 Participants n=63 Participants • Only participants with available data included	9 Participants n=71 Participants • Only participants with available data included	18 Participants n=134 Participants • Only participants with available data included
Centromere(+)	1 Participants n=63 Participants • Only participants with available data included	2 Participants n=71 Participants • Only participants with available data included	3 Participants n=134 Participants • Only participants with available data included

PRIMARY outcome

Timeframe: Measured at study Baseline and Months 3, 6, 12, 15, 18, 21, and 24

Population: Randomized participants with an acceptable baseline HRCT study (a pre-specified covariate) and at least one outcome measure

Outcome measures

Outcome measures
Measure	Mycophenolate Arm n=69 Participants Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Baseline	66.52 FVC %-pred Interval 64.55 to 68.49	66.52 FVC %-pred Interval 64.22 to 68.82
Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 3	66.22 FVC %-pred Interval 64.08 to 69.42	67.03 FVC %-pred Interval 64.64 to 69.42
Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 6	68.02 FVC %-pred Interval 65.55 to 70.49	67.86 FVC %-pred Interval 65.27 to 70.45
Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 9	68.11 FVC %-pred Interval 65.55 to 70.67	69.42 FVC %-pred Interval 66.34 to 72.5
Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 12	68.43 FVC %-pred Interval 65.48 to 71.38	69.86 FVC %-pred Interval 66.82 to 72.9
Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 15	69.84 FVC %-pred Interval 67.14 to 72.54	71.94 FVC %-pred Interval 68.4 to 75.48
Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 18	70.57 FVC %-pred Interval 67.57 to 73.57	72.57 FVC %-pred Interval 69.53 to 75.61
Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 21	70.87 FVC %-pred Interval 67.91 to 73.83	72.55 FVC %-pred Interval 69.18 to 75.92
Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 24	69.65 FVC %-pred Interval 66.53 to 72.77	70.15 FVC %-pred Interval 66.88 to 73.42

SECONDARY outcome

Timeframe: Measured at study entry and Months 6, 12, 18, and 24

Population: Randomized participants with an acceptable baseline HRCT study (a pre-specified covariate) and at least one outcome measure

The TLC represents the total volume of air within the lung after taking the deepest breath possible and the TLC %-predicted represents the TLC expressed as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity. The TLC %-predicted is reduced in patients with interstitial lung disease and is used as a measure of disease severity.

Outcome measures

Outcome measures
Measure	Mycophenolate Arm n=69 Participants Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Total Lung Capacity (TLC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 24	68.24 TLC %-pred Interval 64.99 to 71.49	66.97 TLC %-pred Interval 63.42 to 70.52
Total Lung Capacity (TLC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Baseline	66.16 TLC %-pred Interval 63.74 to 68.58	65.49 TLC %-pred Interval 62.72 to 68.26
Total Lung Capacity (TLC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 6	67.84 TLC %-pred Interval 65.35 to 70.33	67.39 TLC %-pred Interval 64.3 to 70.48
Total Lung Capacity (TLC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 12	67.31 TLC %-pred Interval 64.45 to 70.17	68.25 TLC %-pred Interval 64.93 to 71.57
Total Lung Capacity (TLC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 18	68.50 TLC %-pred Interval 65.45 to 71.55	69.63 TLC %-pred Interval 65.65 to 73.61

SECONDARY outcome

Timeframe: Measured at study entry and Months 3, 6, 12, 15, 18, 21, and 24

Population: Randomized participants with an acceptable baseline HRCT study (a pre-specified covariate) and at least one outcome measure

The DLCO is a pulmonary function test that measures the capacity for the lung to carry out gas exchange between the inhaled breath and the pulmonary capillary blood vessels and the DLCO %-predicted represents the DLCO expressed as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity. The DLCO %-predicted is reduced in patients with interstitial lung disease and is used as a measure of disease severity.

Outcome measures

Outcome measures
Measure	Mycophenolate Arm n=69 Participants Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Baseline	53.99 DLCO %-pred Interval 51.35 to 56.63	54.05 DLCO %-pred Interval 50.8 to 57.3
Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 3	53.38 DLCO %-pred Interval 50.48 to 56.28	51.92 DLCO %-pred Interval 48.34 to 55.5
Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 6	54.86 DLCO %-pred Interval 51.27 to 58.45	50.87 DLCO %-pred Interval 46.84 to 56.28
Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 9	54.13 DLCO %-pred Interval 50.5 to 57.76	51.55 DLCO %-pred Interval 47.09 to 56.01
Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 12	55.32 DLCO %-pred Interval 51.31 to 59.33	53.12 DLCO %-pred Interval 48.38 to 57.86
Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 15	57.77 DLCO %-pred Interval 54.2 to 61.34	53.62 DLCO %-pred Interval 48.29 to 58.95
Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 18	56.62 DLCO %-pred Interval 52.84 to 60.4	55.9 DLCO %-pred Interval 50.82 to 60.98
Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 21	55.47 DLCO %-pred Interval 51.39 to 59.55	54.26 DLCO %-pred Interval 49.29 to 59.23
Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value Month 24	55.31 DLCO %-pred Interval 51.64 to 58.98	52.90 DLCO %-pred Interval 48.71 to 57.09

SECONDARY outcome

Timeframe: Measured at baseline and Month 24

Population: Analysis was carried out in the subset of subjects that had measurable HRCT scans at both study entry and 24 months

Imaging of the whole lung (WL) is performed using a volumetric high resolution computerized tomography (HRCT) scan, which is then analyzed using a computer algorithm to determine the percentage of overall pixels exhibiting features characteristic for quantitative lung fibrosis (QLF). Higher percentages for QLF-WL therefore represent greater involvement by lung fibrosis.

Outcome measures

Outcome measures
Measure	Mycophenolate Arm n=69 Participants Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Fibrosis Score, as Measured by Thoracic High Resolution Computerized Tomography (HRCT) Baseline	8.25 % of lung exhibiting QLF Interval 6.58 to 9.92	8.91 % of lung exhibiting QLF Interval 7.26 to 10.56
Fibrosis Score, as Measured by Thoracic High Resolution Computerized Tomography (HRCT) Month 24	7.99 % of lung exhibiting QLF Interval 6.14 to 9.84	8.48 % of lung exhibiting QLF Interval 6.33 to 10.63

SECONDARY outcome

Timeframe: Measured at Months 6, 12, 18, and 24

Population: Randomized participants with an acceptable baseline HRCT study (a pre-specified covariate) and at least one outcome measure

Change in breathlessness was assessed using the Transitional Dyspnea Index, which compares current symptoms to those at baseline. Total score ranges from - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea.

Outcome measures

Outcome measures
Measure	Mycophenolate Arm n=69 Participants Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Transitional Dyspnea Index Score Month 6	0.74 Transitional Dyspnea Index Score Interval -0.07 to 1.55	0.31 Transitional Dyspnea Index Score Interval -0.43 to 1.05
Transitional Dyspnea Index Score Month 12	1.17 Transitional Dyspnea Index Score Interval 0.23 to 2.11	1.23 Transitional Dyspnea Index Score Interval 0.14 to 2.32
Transitional Dyspnea Index Score Month 18	0.91 Transitional Dyspnea Index Score Interval -0.01 to 1.83	1.78 Transitional Dyspnea Index Score Interval 0.47 to 3.09
Transitional Dyspnea Index Score Month 24	1.86 Transitional Dyspnea Index Score Interval 0.62 to 3.1	2.09 Transitional Dyspnea Index Score Interval 0.8 to 3.38

SECONDARY outcome

Timeframe: Measured at study entry and Months 3, 6, 9, 12, 15, 18, 21, and 24

Population: The analysis population contains all of those with data available at the defined time point.

The HAQ-DI asks questions related to 8 activity domains (dressing, arising, eating, walking, hygiene, reach, grip, and common daily activities) with the patient's capacity to carry out each activity scored from 0 to 3. Scores across all domains are averaged and a higher score represents greater disability.

Outcome measures

Outcome measures
Measure	Mycophenolate Arm n=69 Participants Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI) Baseline	0.71 HAQ-DI Total Score Standard Deviation 0.62	0.74 HAQ-DI Total Score Standard Deviation 0.73
Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI) Month 3	0.83 HAQ-DI Total Score Standard Deviation 0.72	0.64 HAQ-DI Total Score Standard Deviation 0.67
Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI) Month 6	0.75 HAQ-DI Total Score Standard Deviation 0.71	0.58 HAQ-DI Total Score Standard Deviation 0.65
Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI) Month 9	0.66 HAQ-DI Total Score Standard Deviation 0.66	0.65 HAQ-DI Total Score Standard Deviation 0.62
Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI) Month 12	0.64 HAQ-DI Total Score Standard Deviation 0.67	0.56 HAQ-DI Total Score Standard Deviation 0.60
Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI) Month 15	0.58 HAQ-DI Total Score Standard Deviation 0.62	0.62 HAQ-DI Total Score Standard Deviation 0.63
Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI) Month 18	0.55 HAQ-DI Total Score Standard Deviation 0.55	0.55 HAQ-DI Total Score Standard Deviation 0.66
Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI) Month 21	0.65 HAQ-DI Total Score Standard Deviation 0.65	0.48 HAQ-DI Total Score Standard Deviation 0.53
Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI) Month 24	0.62 HAQ-DI Total Score Standard Deviation 0.69	0.57 HAQ-DI Total Score Standard Deviation 0.68

SECONDARY outcome

Timeframe: Measured at baseline and Months 3, 6, 9, 12, 15, 18, 21, and 24

Population: Randomized participants with an acceptable baseline HRCT study (a pre-specified covariate) and at least one outcome measure

Skin thickness is quantified using the modified Rodnan measurement method (mRSS), with a scale that ranges from 0 (no skin involvement) to a maximum of 51. The reported skin score is determined by a clinical assessment of skin thickness, which is performed by a trained reader, and represents the sum of individual assessments that are made in each of 17 body areas. Each area is given a score in the range of 0-3 (0 = normal; 1= mild thickness; 2 = moderate; 3 = severe thickness). A higher score represents more severe skin involvement.

Outcome measures

Outcome measures
Measure	Mycophenolate Arm n=69 Participants Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS) Baseline	15.32 mRSS score Interval 12.85 to 17.79	14.04 mRSS score Interval 11.58 to 16.5
Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS) Month 3	16.03 mRSS score Interval 13.44 to 18.62	12.85 mRSS score Interval 10.17 to 15.53
Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS) Month 6	14.37 mRSS score Interval 11.75 to 16.99	11.95 mRSS score Interval 9.27 to 14.63
Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS) Month 9	14.33 mRSS score Interval 11.62 to 17.04	10.61 mRSS score Interval 8.27 to 12.95
Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS) Month 12	12.45 mRSS score Interval 10.05 to 14.85	9.47 mRSS score Interval 7.35 to 11.59
Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS) Month 15	12.43 mRSS score Interval 10.08 to 14.78	9.80 mRSS score Interval 7.66 to 11.94
Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS) Month 18	11.98 mRSS score Interval 9.48 to 14.48	9.87 mRSS score Interval 7.6 to 12.14
Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS) Month 21	11.22 mRSS score Interval 8.74 to 13.7	8.50 mRSS score Interval 6.19 to 10.81
Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS) Month 24	11.40 mRSS score Interval 8.91 to 13.89	7.87 mRSS score Interval 5.85 to 9.89

SECONDARY outcome

Timeframe: Measured throughout the 2-year study

Outcome measures

Outcome measures
Measure	Mycophenolate Arm n=69 Participants Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death Leukopenia (<2.5x10^3 WBC/microliter)	4 Participants	30 Participants
Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death Neutropenia (<1.0x10^3 neutrophils/microliter)	3 Participants	7 Participants
Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death Anemia (Hgb <10 g/dl)	8 Participants	13 Participants
Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death Thrombocytopenia (<100x10^3 platelets/microliter)	0 Participants	4 Participants
Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death Hematuria (>10 RBC/high power field)	3 Participants	2 Participants
Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death Pneumonia	5 Participants	4 Participants
Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death SAE-Total	27 Participants	22 Participants
Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death SAE-related to treatment	3 Participants	7 Participants
Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death Deaths	5 Participants	11 Participants

SECONDARY outcome

Timeframe: Continuous assessment from randomization to 24 months

The number of participants who remained in the study at the listed time points are reported

Outcome measures

Outcome measures
Measure	Mycophenolate Arm n=69 Participants Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 Participants Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure. Baseline	69 Participants	73 Participants
Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure. Month 3	66 Participants	64 Participants
Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure. Month 6	58 Participants	56 Participants
Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure. Month 9	55 Participants	51 Participants
Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure. Month 12	52 Participants	46 Participants
Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure. Month 15	52 Participants	44 Participants
Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure. Month 18	49 Participants	42 Participants
Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure. Month 21	49 Participants	39 Participants
Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure. Month 24	49 Participants	38 Participants

Adverse Events

Mycophenolate Arm

Serious events: 27 serious events

Other events: 68 other events

Deaths: 0 deaths

Cyclophosphamide Arm

Serious events: 22 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mycophenolate Arm n=69 participants at risk Participants treated with oral mycophenolate mofetil for 2 years. Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated	Cyclophosphamide Arm n=73 participants at risk Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year. Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer	2.9% 2/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	1.4% 1/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Renal and urinary disorders Renal and Bladder	1.4% 1/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	1.4% 1/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Nervous system disorders Syncope and Seizure	2.9% 2/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	0.00% 0/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Blood and lymphatic system disorders Hematologic	1.4% 1/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	2.7% 2/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Gastrointestinal disorders Gastrointestinal	2.9% 2/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	5.5% 4/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Musculoskeletal and connective tissue disorders Musculoskeletal	5.8% 4/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	4.1% 3/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Infections and infestations Respiratory Infection	2.9% 2/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	9.6% 7/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Respiratory, thoracic and mediastinal disorders Respiratory Events	10.1% 7/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	6.8% 5/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Cardiac disorders Cardiac	11.6% 8/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	11.0% 8/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
General disorders Weakness	0.00% 0/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	1.4% 1/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Injury, poisoning and procedural complications Medication Reaction	1.4% 1/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	0.00% 0/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Injury, poisoning and procedural complications Injury	1.4% 1/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	0.00% 0/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Surgical and medical procedures Elective Surgery	2.9% 2/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	0.00% 0/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments
Infections and infestations Abscess	1.4% 1/69 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments	0.00% 0/73 • Randomization to withdrawal from taking study drug or completion of the 24 month treatment protocol. An organ system designation was developed for the study and applied in a systematic manner to all adverse event assessments

Other adverse events

Additional Information

Donald P. Tashkin, M.D.

David Geffen School of Medicine at UCLA

Phone: 310-825-5316

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place