Combined Treatment of Methotrexate + Glucocorticoids Versus Glucocorticoids Alone in Patients With PM and DM

NCT00651040 | Completed Phase 3 Results

• 1 other identifier: 3401
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Therapeutical trial in patients with idiopathic polymyositis (PM) and dermatomyositis (DM) is proposed. The study will investigate the safety and efficacy of combined methotrexate (MTX) + glucocorticoids (GC) treatment compared with GC alone. This will be a randomised, open-label, assessor-blind, international multicenter trial, performed in several European centres interested in research on inflammatory myopathies (IIM). A total number of 50 patients with PM/DM will be randomised into two groups (1: MTX+ GC and 2: GC only). Patients will be equally distributed between the two groups providing 25 patients per treatment arm. The randomisation will be based on random numbers generated by a computer program. After being enrolled in the study, the patients will receive 12 months of therapy followed by a 12-month follow-up period. The primary endpoint is the total dose of GC ( in mg/kg weight), which will be administered for 12 months between baseline and the end of treatment. There are several of secondary objectives, which will be pursued during and after the trial. Disease activity and damage will be prospectively assessed by tools for myositis disease activity (MYOACT and MITAX) and for myositis damage (MYODAM and MDI), global assessment of activity and damage by patients and by physician, muscle endurance, muscle strength by manual muscle testing, enzyme levels, GC related side effects, functional ability measured by HAQ, quality of life by SF-36, and number of patients with treatment failures. The other aims will also include (i) search for reliable prognostic parameters in the further prognosis of patients with PM/DM and (ii) studies on the pathogenic aspects of IIM. The investigations of serum, lymphocytes, muscle tissue and MRI will be organized. DNA and RNA will be stored for future genetic studies. Patients with definite or probable PM or DM diagnosed according to diagnostic criteria will be enrolled. They will have disease activity that according to physician's own judgement requires high dose immunosuppressive treatment (based on clinical assessment of weakness, elevation of muscle enzymes and, if available, on magnetic resonance imaging findings). Patients should be previously untreated with the exception of GC treatment up to 8 weeks. Patients with other than primary idiopathic PM or DM, such as drug-induced myositis, myositis in association with other connective tissue disease, inclusion body myositis, malignancy related myositis, and juvenile DM will be excluded. All patients will start with prednisone 1 mg/kg/day and the dose will be tapered if patients meet definition of improvement, which has been proposed by IMACS group. MTX will be administered orally, once weekly, with a starting dose 10 mg. This will be increased gradually to 25 mg/week if tolerated by week 5. Patients will be first assessed after 2 weeks and than monthly for a period of 48 weeks. There will be a follow-up after a further 1 year in order to find out the impact of the early treatment on the long-term disease outcome. All efficacy analyses will be performed using intention-to-treat population (ITT). In addition, the primary and secondary variables will be analysed using the per-protocol population, which will contain all patients in the ITT population, who also reached Week 48 without any major protocol violations. The safety population, which will contain any patient who received at least one dose of study drug, will be used for all safety analyses.

Conditions

Polymyositis; Dermatomyositis

Keywords

Polymyositis; Dermatomyositis; Glucocorticoids; Methotrexate

Outcome Measures

Primary Outcomes (1)

• The Primary Endpoint is the Total Dose of Glucocorticoids Administered Between Baseline and the End of Treatment.

  The primary endpoint which has benn measured was the total dose of glucocorticoids administered between baseline and the end of treatment.

  1 year

Secondary Outcomes (1)

• Assessment of Disease Activity and Damage,Muscle Strength and Endurance, Enzyme Levels, Glucocorticoid Side-effects, Dose, HAQ,SF-36, Treatment Failures

  1 year

Study Arms (2)

Prednison

ACTIVE COMPARATOR

Prednisone will be administered orally, initially at 1.0 mg/kg/day dosage and then tapered gradually equally in the two arms. ARM 1 has only Prednisone

Drug: Prednisone

Prednison + methotrexate

ACTIVE COMPARATOR

MTX will be administered orally (in case of oral intolerance intramusculary (i.m.)), once weekly for 48 weeks. There will be a clinically oriented dose escalation starting from 10 up to 20-25 mg of MTX. Five to ten mg of folic acid will be given 24 hours after each methotrexate dose.

Drug: Prednisone; Drug: Methotrexate

Interventions

Prednisone DRUG

Prednisone will be administered orally, initially at 1.0 mg/kg/day dosage and then tapered gradually equally in the two arms

Also known as: Prednisolone

Prednison; Prednison + methotrexate

Methotrexate DRUG

MTX will be administered orally (in case of oral intolerance intramusculary (i.m.)), once weekly for 48 weeks. There will be a clinically oriented dose escalation starting from 10 up to 20-25 mg of MTX. Five to ten mg of folic acid will be given 24 hours after each methotrexate dose.

Prednison + methotrexate

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 - 80 years.
• Patients with definite or probable polymyositis or dermatomyositis diagnosed according to diagnostic criteria (9, 10) (Appendix 1)
• Physician's own judgment of the disease activity that requires high dose immunosuppressive treatment (based on clinical assessment of weakness, elevation of muscle enzymes and, if available, on magnetic resonance imaging findings).
• Previously untreated patients with the exception of glucocorticoid treatment up to 8 weeks
• Signed informed consent.

You may not qualify if:

• Treatment with any immunosuppressive drug prior the study start.
• Treatment with glucocorticoids (\> 20 mg of Prednisone or equivalent) more than 8 weeks prior to study start.
• Drug induced myositis.
• Polymyositis and dermatomyositis in association with other connective tissue disease.
• Patients with immunodeficiency syndrome.
• Pregnancy and lactation.
• Fertile women not using adequate contraception during the study, women planning to have children during the study course or 12 months after the end of the study.
• Malignancy.
• Juvenile dermatomyositis.
• Uncontrolled, clinically significant hematological, cardiovascular, pulmonary, endocrine, metabolic, gastrointestinal, hepatic or renal disease, which according to physician's consideration would interfere with high dose glucocorticoid and immunosuppressive treatment or would prevent to follow the treatment protocol.
• Severe infection.
• History of drug or alcohol abuse within the previous 6 months.
• Patients known to be HIV positive.
• Known hypersensitivity to methotrexate.

Sponsors & Collaborators

• Institute of Rheumatology, Prague: lead
• Karolinska Institutet: collaborator

Study Sites (1)

Revmatologicky ustav

Prague, 12850, Czechia

Location

MeSH Terms

Conditions

Polymyositis; Dermatomyositis

Interventions

Prednisone; Prednisolone; Methotrexate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Rheumatology Institute Prague
• Organization: Rheumatology Institute Prague

vencovsky@revma.cz

+420234075111

Study Officials

• Jiri Vencovsky, prof. MD.

  Institute of Rheumatology, Prague

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2008
• First Posted: April 2, 2008
• Study Start: May 1, 2008
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: May 12, 2016
• Results First Posted: May 12, 2016

Record last verified: 2016-04

Locations

CZ (1)