Investigation in Myositis-associated Pneumonitis of Prednisolone And Concomitant Tacrolimus

NCT00504348 | Completed Phase 2 Results

• 1 other identifier: IICT-FK506-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Interstitial Pneumonitis; Polymyositis; Dermatomyositis

Keywords

Interstitial pneumonitis; Polymyositis; Dermatomyositis; Tacrolimus; Corticosteroids

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival (OS) was calculated from the day on which the protocol treatment was started until death due to any cause. Participants still alive were censored at the date they were last known to be alive.

  52 weeks

Secondary Outcomes (1)

• Progression-free Survival

  52 weeks

Study Arms (1)

Prospective investigation group

EXPERIMENTAL

Tacrolimus treatment is to be initiated at the starting dose of 0.075mg/kg/day, adjusted to maintain its whole blood trough levels between 5 and 10 ng/mL for 52 weeks. All patients are to receive glucocorticoids with the starting doses equivalent to between 0.6 and 1.0 mg/kg/day of prednisolone which are to be continued for the first 28 days after which be subsequently tapered according to a predefined guideline. Up to two courses of pulse intravenous glucocorticoid therapy are allowed during that period.

Drug: Tacrolimus

Interventions

Tacrolimus DRUG

Start at the standard starting dose of 0.075mg/kg/day divided into two doses, then adjust doses based on clinical response and tolerability, but maintain whole blood trough levels between 5 to 10 ng/mL and total daily doses equal to or below 0.3mg/kg.

Also known as: Prograf

Prospective investigation group

Eligibility Criteria

• Age: 16 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Experimental treatment group
• 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
• 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)
• 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
• to 74 years of age
• Historical control group
• 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
• 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)
• 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
• to 74 years of age

You may not qualify if:

• Experimental treatment group
• 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
• Use of immunosuppressive agents other than corticosteroids within 12 weeks (84 days) prior to the initiation of the study drug
• Could not exclude the following conditions on clinical ground: drug-induced pneumonitis, occupational lung disease, hypersensitivity pneumonitis, radiation-induced lung injury
• 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
• Presence of pancreatitis
• Presence of diabetes mellitus with the exception of glucocorticoid-induced one that is well-controlled (HbA1c \< 6.5%)
• Serum creatinine of 1.5 mg/dL or above
• 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
• Serum potassium above the upper limit of normal
• Presence of ischemic heart disease, arrhythmia requiring treatment, congestive heart failure, or pulmonary hypertension requiring treatment
• Presence or history of malignancy with the exception of those without relapse off treatment for 5 years or longer
• Presence of serious active infection
• Presence of active hepatitis B, hepatitis C, or HIV infection
• History of severe drug hypersensitivity reaction

Sponsors & Collaborators

• Tokyo Medical and Dental University: lead
• Japan Medical Association: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (11)

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Tsukuba University Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Osaka Minami Medical Center

Kawachi-Nagano, Osaka, 586-8521, Japan

Location

Juntendo University Hospital

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

Tokyo Medical and Dental University Hospital

Bunkyo-ku, Tokyo, 113-8519, Japan

Location

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, 113-8655, Japan

Location

Keio University Hospital

Shinjuku-ku, Tokyo, 160-8582, Japan

Location

International Medical Center of Japan

Shinjuku-ku, Tokyo, 162-8655, Japan

Location

Chiba University Hospital

Chiba, 260-8677, Japan

Location

Nagasaki University Hospital of Medicine and Dentistry

Nagasaki, 852-8501, Japan

Location

Tokushima University Hospital

Tokushima, 770-8503, Japan

Location

Related Publications (1)

• Takada K, Katada Y, Ito S, Hayashi T, Kishi J, Itoh K, Yamashita H, Hirakata M, Kawahata K, Kawakami A, Watanabe N, Atsumi T, Takasaki Y, Miyasaka N. Impact of adding tacrolimus to initial treatment of interstitial pneumonitis in polymyositis/dermatomyositis: a single-arm clinical trial. Rheumatology (Oxford). 2020 May 1;59(5):1084-1093. doi: 10.1093/rheumatology/kez394.

  PMID: 31539061 RESULT

MeSH Terms

Conditions

Lung Diseases, Interstitial; Polymyositis; Dermatomyositis

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Conclusion is not based on meaningful statistical comparison, will not apply to asymptomatic or subclinical IP, or to the exacerbation of IP, or will not separately provide the efficacy of the treatment in the anti-MDA-5 positive subgroup.

Results Point of Contact

• Title: Kazuki Takada, M.D.
• Organization: Tokyo Medical and Dental University

takada.rheu@tmd.ac.jp

81-3-3813-6111

Study Officials

• Nobuyuki Miyasaka, MD, PhD

  Tokyo Medical and Dental University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Institute of Education

Study Record Dates

• First Submitted: July 19, 2007
• First Posted: July 20, 2007
• Study Start: July 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: March 24, 2020
• Results First Posted: March 24, 2020

Record last verified: 2020-03

Locations

JP (11)