Five-year Actively Controlled Clinical Trial in New Onset Juvenile Dermatomyositis

NCT00323960 | Completed Phase 3 Results

• 3 other identifiers: IGG-PRINTO-002AIFAMyositis Association
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 5-year project, involving 185 partners from 46 countries ((110 in 21 European Union (EU) States and 75 in 25 extra-EU States)), with a randomised clinical trials (RCT) in juvenile dermatomyositis (JDM): 5-year phase III single-blind, RCT in children with newly diagnosed JDM: prednisone (PDN) versus PDN plus methotrexate (MTX) versus PDN plus Cyclosporine A. The trial is aimed to find out the treatment regimen associated with the lowest occurrence of flare and the lowest drug related toxicity

Conditions

Juvenile Dermatomyositis

Keywords

Juvenile dermatomyositis; randomised actively controlled clinical trial; prednisone; cyclosporine; methotrexate; effectiveness

Outcome Measures

Primary Outcomes (2)

• Responder Status Defined as 20% Improvement in at Least 3 Core Set Variables With no More Than 1 of the Remaining Variables, (Muscle Strength Excluded), Worsened by > 30%.

  The PRINTO Juvenile Dermatomyositis (JDM) core set variables are: 1. muscle strength by the mean of the Childhood Myositis Assessment Scale (CMAS); 2. physician's global assessment of disease activity on a 10 cm Visual Analogue Scale (VAS); 3. global disease activity assessment by the mean of the Disease Activity Index (DAS); 4. parent's/patient's global assessment of overall well-being on a 10 cm VAS; 5. functional ability assessment by the mean of the Childhood Health Assessment Questionnaire (CHAQ) 6. health-related quality of life assessment.

  6 months

• Time to Clinical Remission

  Clinical remission is defined as the status of inactive disease for at least 6 continuous months defined as normal muscle strength (CMAS equal to 52) and physician global assessment of disease activity equal to 0.

  60 months

Secondary Outcomes (2)

• Time to Major Therapeutic Changes

  60 months

• Time to Prednisone, or Equivalent, Discontinuation

  60 months

Study Arms (3)

Methylprednisolone pulse (MPDN)+PDN+CSA

ACTIVE COMPARATOR

MPDN= methylprednisolone pulse PDN= prednisone or equivalent CSA= cyclosporine A

Drug: 3 MPDN pulse + PDN + CSA

MPDN+PDN+MTX

ACTIVE COMPARATOR

MPDN= methylprednisolone pulse PDN= prednisone or equivalent MTX= methotrexate

Drug: 3 MPDN pulse + PDN + MTX

MPDN+PDN

ACTIVE COMPARATOR

MPDN= methylprednisolone PDN= prednisone or equivalent

Drug: 3 MPDN pulse + PDN

Interventions

3 MPDN pulse + PDN DRUG

3 methylprednisolone pulses followed (30 mg/kg/pulse max 1 gram) followed by prednisone 2 mg/Kg/day to be tapered to 0.2 mg/kg/day in 6 months and then discontinued in 2 years.

MPDN+PDN

3 MPDN pulse + PDN + CSA DRUG

3 methylprednisolone pulses followed (30 mg/kg/pulse max 1 gram) followed by prednisone 2 mg/Kg/day to be tapered to 0.2 mg/kg/day in 6 months and then discontinued in 2 years; Cyclosporine 5 mg/Kg/day in 2 oral doses

Methylprednisolone pulse (MPDN)+PDN+CSA

3 MPDN pulse + PDN + MTX DRUG

3 methylprednisolone pulses followed (30 mg/kg/pulse max 1 gram) followed by prednisone 2 mg/Kg/day to be tapered to 0.2 mg/kg/day in 6 months and then discontinued in 2 years; Methotrexate 15-20 mg/m2 once per week. Patients treated with MTX will receive concomitant folic or folinic acid according to the attending physician decision.

MPDN+PDN+MTX

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Newly diagnosed and untreated children (only treatment with 1 NSAID is allowed and/or prednisone \>1 mg/kg/day for no more than 1 month from diagnosis) with probable or definite diagnosis of JDM according to published (12;13). If a muscle biopsy will be performed (optional) it will be read by the pathologists of the participating centres (light and immunofluorescence). Slides of paraffin-embedded sections from all patients will be re-viewed by a blinded myopathologist at PRINTO.
• Age at enrolment ≤ 18 years.
• Female of child-bearing potential must have a negative pregnancy test at the beginning of the trial, and then every 3 months. If sexually active, they must agree to use adequate contraception, throughout study participation, and must have no intention of conceiving during the course of the study. Post-pubertal males must have no plans to father a child during the study and agree to use adequate birth control methods if sexually active.
• Ability to comply with the entire study procedures, ability to communicate meaningfully with the investigational staff, competence to give written informed consent; to be applied to the parents and/or patients, as appropriate
• Duly executed, written, informed consent obtained from the parents/patient.

You may not qualify if:

• Neutrophil count \<1,500/mm3 and/or platelet count \<50,000/mm3
• Demonstration of cutaneous or gastrointestinal ulceration of JDM related pulmonary disease or cardiomyopathy at the time of diagnosis.
• History of poor compliance.
• Evidence of current use of alcohol or illicit drugs abuse.
• Live vaccines not allowed during the entire duration of the trial.
• Dropout Criteria. Patients will be considered "treatment failures", and dropped from the trial but included in efficacy analysis, if any of the following will occur during the active period of the trial.
• Non compliance with study medication administration
• Enrolment in other therapeutic trials.

Sponsors & Collaborators

• Istituto Giannina Gaslini: lead
• Pediatric Rheumatology International Trials Organization: collaborator

Study Sites (1)

Istituto Giannina Gaslini

Genoa, 16147, Italy

Location

Related Publications (7)

• Miller LC, Sisson BA, Tucker LB, DeNardo BA, Schaller JG. Methotrexate treatment of recalcitrant childhood dermatomyositis. Arthritis Rheum. 1992 Oct;35(10):1143-9. doi: 10.1002/art.1780351006.

  PMID: 1418005 BACKGROUND

• Al-Mayouf S, Al-Mazyed A, Bahabri S. Efficacy of early treatment of severe juvenile dermatomyositis with intravenous methylprednisolone and methotrexate. Clin Rheumatol. 2000;19(2):138-41. doi: 10.1007/s100670050032.

  PMID: 10791626 BACKGROUND

• Heckmatt J, Hasson N, Saunders C, Thompson N, Peters AM, Cambridge G, Rose M, Hyde SA, Dubowitz V. Cyclosporin in juvenile dermatomyositis. Lancet. 1989 May 13;1(8646):1063-6. doi: 10.1016/s0140-6736(89)92456-2.

  PMID: 2566009 BACKGROUND

• Pistoia V, Buoncompagni A, Scribanis R, Fasce L, Alpigiani G, Cordone G, Ferrarini M, Borrone C, Cottafava F. Cyclosporin A in the treatment of juvenile chronic arthritis and childhood polymyositis-dermatomyositis. Results of a preliminary study. Clin Exp Rheumatol. 1993 Mar-Apr;11(2):203-8.

  PMID: 8508564 BACKGROUND

• Ruperto N, Pistorio A, Ravelli A, Angioloni S, Martini A; Paediatric Rheumatology International Trials Organisation (PRINTO). The PRINTO juvenile dermatomyositis trial - Authors' reply. Lancet. 2016 Jun 25;387(10038):2601. doi: 10.1016/S0140-6736(16)30671-7. No abstract available.

  PMID: 27353819 DERIVED

• Dale A, Milosevic I, Goldacre B; COMPare project team. The PRINTO juvenile dermatomyositis trial. Lancet. 2016 Jun 25;387(10038):2600-2601. doi: 10.1016/S0140-6736(16)30845-5. No abstract available.

  PMID: 27353816 DERIVED

• Ruperto N, Pistorio A, Oliveira S, Zulian F, Cuttica R, Ravelli A, Fischbach M, Magnusson B, Sterba G, Avcin T, Brochard K, Corona F, Dressler F, Gerloni V, Apaz MT, Bracaglia C, Cespedes-Cruz A, Cimaz R, Couillault G, Joos R, Quartier P, Russo R, Tardieu M, Wulffraat N, Bica B, Dolezalova P, Ferriani V, Flato B, Bernard-Medina AG, Herlin T, Trachana M, Meini A, Allain-Launay E, Pilkington C, Vargova V, Wouters C, Angioloni S, Martini A; Paediatric Rheumatology International Trials Organisation (PRINTO). Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial. Lancet. 2016 Feb 13;387(10019):671-678. doi: 10.1016/S0140-6736(15)01021-1. Epub 2015 Nov 30.

  PMID: 26645190 DERIVED

Related Links

• Web site of the international network who is conducting the trial
• Web site for families in 50 different languages with information about the pediatric rheumatic diseases

MeSH Terms

Conditions

Dermatomyositis

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Nicolino Ruperto
• Organization: IRCCS Istituto Giannina Gaslini

nicolaruperto@gaslini.org

+39-010-382854

Study Officials

• Nicolino Ruperto, MD, MPH

  Istituto Giannina Gaslini _ PRINTO Senior Scientist

  PRINCIPAL INVESTIGATOR

• Alberto Martini, MD, Prof.

  Istituto Giannina Gaslini_PRINTO Chairman

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist of PRINTO

Study Record Dates

• First Submitted: May 9, 2006
• First Posted: May 10, 2006
• Study Start: May 31, 2006
• Primary Completion: May 12, 2011
• Study Completion: November 29, 2015
• Last Updated: March 28, 2023
• Results First Posted: March 16, 2021

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Data will be available upon request
• Access Criteria: Request to the Paediatric Rheumatology International Trials Organisation (PRINTO) international coordinating centre: PRINTO@gaslini.org

Locations

IT (1)