Investigation in Myositis-associated Pneumonitis of Prednisolone And Concomitant Tacrolimus

• Status: Completed
• Trial end date: 2011-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the study is to evaluate the efficacy and safety of the combination treatment of tacrolimus and corticosteroid in polymyositis/dermatomyositis patients with interstitial pneumonitis with comparison against corticosteroid-treated historical controls.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tokyo Medical and Dental University
• Collaborators: Astellas Pharma Inc; Japan Medical Association
• Treatments: Tacrolimus

Criteria

Inclusion Criteria:

Experimental treatment group

1. Diagnosis of definite or probable polymyositis or dermatomyositis by criteria of Bohan et al, or of clinically-amyopathic dermatomyositis by the definition proposed by Sontheimer et al

2. High-resolution CT findings consistent with interstitial pneumonitis, confirmed by a radiologist. If consolidation is the only abnormal findings, the patient must have pathologically documented evidence of interstitial pneumonitis of other histological type than cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia (the patient could have more than one histological type including cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia)

3. Meet two or more of the following criteria (must include 1) 1. Serum KL-6 above the upper normal limit 2. Presence of dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index 3. PaO2 of less than 80 mmHg while breathing ambient air at rest, not accompanied by abnormal increase of PaCO2 4. Vital capacity < 80% predicted, or diffusing capacity for carbon monoxide < 65% predicted 5. Meet at least one of the following condition over the 12-week period (84 days) prior to the initiation of the study drug

• Decrease in either % forced vital capacity or % diffusing capacity for carbon monoxide of 10% or more

• Worsening of interstitial pneumonitis findings by chest CT, confirmed by a radiologist

4. 16 to 74 years of age

Historical control group

1. Diagnosis of definite or probable polymyositis or dermatomyositis by criteria of Bohan et al, or of clinically-amyopathic dermatomyositis by the definition proposed by Sontheimer et al

2. High-resolution CT findings consistent with interstitial pneumonitis, confirmed by a radiologist. If consolidation is the only abnormal findings, the patient must have pathologically documented evidence of interstitial pneumonitis of other histological type than cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia (the patient could have more than one histological type including cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia)

3. Meet two or more of the following criteria (must include 1) 1. Serum KL-6 above the upper normal limit 2. Presence of dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index 3. PaO2 of less than 80 mmHg while breathing ambient air at rest, not accompanied by abnormal increase of PaCO2 4. Vital capacity < 80% predicted, or diffusing capacity for carbon monoxide < 65% predicted 5. Meet at least one of the following condition over the 12-week period (84 days) prior to the initiation of the study drug

• Decrease in either % forced vital capacity or % diffusing capacity for carbon monoxide of 10% or more

• Worsening of interstitial pneumonitis findings by chest CT, confirmed by a radiologist

4. Use of corticosteroids at doses equivalent to between 0.6 to 1.0mg/kg/day of prednisolone for 14 days or longer to treat interstitial pneumonitis on or after the day when the inclusion criteria (3) was met (up to two courses of pulse IV corticosteroid therapy within the first 28 days are allowed)

5. 16 to 74 years of age

Exclusion Criteria:

Experimental treatment group

1. Use of corticosteroids at doses equivalent to or higher than prednisolone 0.6mg/kg/day within 4 weeks (28 days) prior to the initiation of the study drug

2. Use of immunosuppressive agents other than corticosteroids within 12 weeks (84 days) prior to the initiation of the study drug

3. Could not exclude the following conditions on clinical ground: drug-induced pneumonitis, occupational lung disease, hypersensitivity pneumonitis, radiation-induced lung injury

4. Presence of end-stage interstitial pneumonitis as identified on the basis of a vital capacity < 45% predicted, diffusing capacity for carbon monoxide < 30% predicted, or lung CT with predominantly honeycombing appearance

5. Presence of pancreatitis

6. Presence of diabetes mellitus with the exception of glucocorticoid-induced one that is well-controlled (HbA1c < 6.5%)

7. Serum creatinine of 1.5 mg/dL or above

8. Presence of liver dysfunction (AST(GOT) or ALT (GPT) greater than 2.5 times the upper limit of normal) with the exception of the one that is considered to be due to myositis and is accompanied by the elevation of muscle enzymes above the upper limit of normal

9. Serum potassium above the upper limit of normal

10. Presence of ischemic heart disease, arrhythmia requiring treatment, congestive heart failure, or pulmonary hypertension requiring treatment

11. Presence or history of malignancy with the exception of those without relapse off treatment for 5 years or longer

12. Presence of serious active infection

13. Presence of active hepatitis B, hepatitis C, or HIV infection

14. History of severe drug hypersensitivity reaction

15. Patients who are pregnant or breast-feeding, or patients who intend to or whose spouses intend to conceive during the course of the study, including the follow-up period

16. Participation in another clinical trial or post-marketing clinical study within 26 weeks (182 days) prior to screening

17. Other medical condition which, in the investigator's judgment, may be associated with increased risk to the subject or may interfere with study assessments or outcomes

Historical control group

1. Use of immunosuppressive agents other than corticosteroids within 12 weeks (84 days) prior to or 2 weeks (14 days) after the corticosteroid treatment as defined by the inclusion criteria (4) is initiated

2. Could not exclude the following conditions on clinical ground: drug-induced pneumonitis, occupational lung disease, hypersensitivity pneumonitis, radiation-induced lung injury

3. Presence of end-stage interstitial pneumonitis as identified on the basis of a vital capacity < 45% predicted, diffusing capacity for carbon monoxide < 30% predicted, or lung CT with predominantly honeycombing appearance

4. Presence of pancreatitis

5. Presence of diabetes mellitus with the exception of glucocorticoid-induced one that is well-controlled (HbA1c < 6.5%)

6. Serum creatinine of 1.5 mg/dL or above

7. Presence of liver dysfunction (AST(GOT) or ALT (GPT) greater than 2.5 times the upper limit of normal) with the exception of the one that is considered to be due to myositis and is accompanied by the elevation of muscle enzymes above the upper limit of normal

8. Serum potassium above the upper limit of normal

9. Presence of ischemic heart disease, arrhythmia requiring treatment, congestive heart failure, or pulmonary hypertension requiring treatment

10. Presence or history of malignancy with the exception of those without relapse off treatment for 5 years or longer

11. Presence of serious active infection including active hepatitis B, hepatitis C, or HIV infection

12. Other medical condition which, in the investigator's judgment, may be associated with increased risk to the subject or may interfere with study assessments or outcomes