Condition category
Skin and Connective Tissue Diseases
Date applied
23/10/2006
Date assigned
21/12/2006
Last edited
01/10/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Patrick Dupuy

ORCID ID

Contact details

ORFAGEN
CRDPF - LANGLADE
3 avenue Hubert Curien - BP 13562
Toulouse Cedex 1
31 035
France

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

L00133 IV 301 (ORF)

Study information

Scientific title

Acronym

Study hypothesis

Primary objective:
To assess the efficacy of the L0133 product as adjunctive treatment to conventional glucocorticosteroids (GS) and immunosuppressors (IS) in dermatomyositis (DM) and polymyositis (PM) patients with insufficient improvement of muscle strength.

Secondary objective:
To assess the overall safety profile of the intravenous immunoglobulin (IVIg) product in DM and PM patients.

As of 18/01/2008 this record was updated. Changes are written under the relevant sections under the above update date. Please also note that the anticipated end date of this trial has been extended; the initial anticipated end date of this trial was 21/03/2008.

As of 14/08/2009 this record was again updated; all updates can be found under the relevant field with the above update date. At this time, the anticipated end date was also updated; the previous anticipated end date of this trial was 31/08/2009.

As of 09/12/2010 this record was again updated; all updates can be found under the relevant field with the above update date. At this time, the anticipated end date was also updated; the previous anticipated end date of this trial was 31/07/2010.

Please note that as of 01/10/2012, the anticipated end date of this trial was updated from 31/12/2012 to 06/09/2011. This was the final completion date of the study.

Ethics approval

Positive opinions from the Ethics Committees in:
1. Austria: approved on 25/01/2007
2. France: approved on 06/03/2006
3. Germany: approved on 18/07/2006
4. Italy: Ancona site approved on 20/07/2006

Added 14/08/2009:
5. Italy: Pisa site approved on 18/09/2008

Added 09/12/2010:
6. Hungary: approved on 21/01/2010
7. Czech Republic: approved on 16/12/2009
8. Mexico: approved on 22/01/2010

Study design

Run-in period: observational study; period I: randomised, double-blind, placebo-controlled, two-parallel groups design; period II: open-labelled, non comparative, one-arm design

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Dermatomyositis (DM) and polymyositis (PM)

Intervention

The study will comprise three periods:
1. Run-in period: observational period, in which patients under conventional therapies (GS, IS) will be followed. Only patients with an insufficient improvement on muscle strength will be allowed to enter Period I.
2. Period I: randomised, double-blind, placebo-controlled, two-parallel groups design (stratification between DM and PM patients).
3. Period II: open-labelled, non comparative, one-arm design.

1. L0133 product: 2 g/Kg (40 ml/Kg) IV per month, delivered in two consecutive days (1 g/Kg daily or 20 ml/Kg daily) during period I and period II
2. Placebo: 40 ml/Kg IV per month, delivered in two consecutive days (20 mL/Kg daily) during period I only

Intervention type

Drug

Phase

Not Applicable

Drug names

Prednisone, methotrexate, intravenous immunoglobulin product (L0133)

Primary outcome measures

1. Muscle strength intensity, as defined by the BMRC.
2. Treatment response will be defined as an improvement from baseline of BMRC score at the end of Period I.

Secondary outcome measures

1. Time course evaluation of muscle strength using BMRC index (run-in period, Period I and Period II).
2. Physical function recorded by the patients, as measured by the Health Assessment Questionnaire (HAQ) scale.
3. Visual Analogue Scale (VAS) global disease activity made by the Investigators and the patients
4. Serum activity of muscle enzymes - Measurement outcome as defined by International Myositis Assessment and Clinical Studies Group (IMACS).
5. Cutaneous signs severity, according to the modified three-point scale from Göttfried
6. Other organ involvement (cardiac, pharyngeal, gastro-intestinal, joint, pulmonary, others) assessed by the Investigators, using clinical and paraclinical examinations.
7. Consumption of prednisone during the run-in period, Period I and Period II.
8. Consumption of IS during period II.
9. Routine blood laboratory tests (haematology, chemistry).
10. Adverse events.

Overall trial start date

21/09/2006

Overall trial end date

06/09/2011

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 14/08/2009:
1. Male or female patients of at least 18 years of age
2. Patients fulfilling the diagnostic criteria (definite or probable) of the European Neuromuscular Committee (ENMC) for idiopathic DM and PM
3.1. Patients with an active DM or PM disease who received conventional therapies for at least 14 weeks: oral prednisone 1 mg/kg per day for at least 4 weeks, with or without immunosuppressors (IS), followed by IS at stable dose and prednisone for at least 10 weeks, or
3.2. Patients with a contra-indication or a major side-effect to prednisone or methotrexate/other IS, or
3.3. Patients under biotherapy with a documented deterioration of their British Medical Research Council (BMRC) score, or
3.4. DM patients under biotherapy having a documented deterioration of their cutaneous signs, or
3.5. Patients under biotherapy with an onset of visceral involvement
4. Patients with no significant improvement of muscle strength under conventional therapy
5. Patients with BMRC index between 24 and 72 at baseline

Previous inclusion criteria as of 18/01/2008:
1. Male or female patients of at least 18 years of age
2. Patients fulfilling the diagnostic criteria (definite or probable) of the European Neuromuscular Committee (ENMC) for idiopathic DM and PM
3. Patients with an active DM or PM disease who received conventional therapies for at least 14 weeks: oral prednisone 1 mg/Kg per day, immunosuppressors at stable dosage
4. Patients with no significant improvement of muscle strength under conventional therapy, i.e. with an improvement of their muscle British Medical Research Council (BMRC) index of less than 18 points at baseline compared to the beginning of the run-in period
5. Patients with BMRC index between 32 and 64 at baseline

Initial inclusion criteria:
1. Male or female patients of at least 18 years of age
2. Patients fulfilling the diagnostic criteria (definite or probable) of the European Neuromuscular Committee (ENMC) for idiopathic DM and PM
3. Patients with an active DM or PM disease who received conventional therapies for at least 18 weeks: oral prednisone 1 mg/Kg per day, Methotrexate 15 mg per week
4. Patients with no significant improvement of muscle strength under conventional therapy, i.e. with an improvement of their muscle British Medical Research Council (BMRC) index of less than 18 points at baseline compared to the beginning of the run-in period
5. Patients with BMRC index between 32 and 64 at baseline

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

44 patients

Participant exclusion criteria

Current exclusion criteria as of 14/08/2009:
1. Pregnant women, nursing mothers and women of childbearing potential with no reliable contraception
2. Patients who do not fulfil the ENMC diagnostic criteria (definite or probable) of idiopathic DM and PM
3. Patients with a diagnosis of paraneoplasic DM or PM
4. Juvenile DM and PM (age less than 18 years)
5. DM patients with no muscle involvement
6. Patients with life expectancy of less than three months
7. Patients whose muscle strength is responsive to conventional therapy, i.e. with an improvement of at least 18 points of their BMRC index at baseline compared to the beginning of the run-in period if BMRC below 40,5 at first run-in period assessment, 12 points if BMRC between 40.5 and 56 included at first run-in period assessment and 8 points if BMRC over 56 at first run-in period assessment
8. Patients with an BMRC index of less than 24 or more than 72
9. Patients having received a bolus of methylprednisone within three weeks prior to study entry
10. Patients with a known allergy to one of the ingredients of the IVIg test product
11. Patients with decompensated cardiac insufficiency or any other inter-current condition that may alter the study conduct
12. Patients with positive Coomb's test at baseline

Previous exclusion criteria as of 18/01/2008:
1. Pregnant women, nursing mothers and women of childbearing potential with no reliable contraception
2. Patients who do not fulfil the ENMC diagnostic criteria (definite or probable) of idiopathic DM and PM
3. Patients with a diagnosis of paraneoplasic DM or PM
4. Juvenile DM and PM (age less than 18 years)
5. DM patients with no muscle involvement
6. Patients with life expectancy of less than three months
7. Patients with severe forms of DM and PM: pharyngeal, cardiac or pulmonary involvement
8. Patients without conventional treatments as first-line therapy for at least 14 weeks: oral prednisone 1 mg/Kg per day, immunosuppressors at stable dosage
9. Patients whose muscle strength is responsive to conventional therapy, i.e. with an improvement of at least 18 points of their BMRC index at baseline compared to the beginning of the run-in period
10. Patients with a BMRC index of less than 32 or more than 64
11. Patients having received a bolus of methylprednisone within three months prior to study entry
12. Patients with a known allergy to one of the ingredients of the IVIg test product
13. Patients with decompensated cardiac insufficiency or any other inter-current condition that may alter the study conduct
14. Patients with positive Coomb's test at baseline

Initial exclusion criteria:
1. Pregnant women, nursing mothers and women of childbearing potential with no reliable contraception
2. Patients who do not fulfil the ENMC diagnostic criteria (definite or probable) of idiopathic DM and PM
3. Patients with a diagnosis of paraneoplasic DM or PM
4. Juvenile DM and PM (age less than 18 years)
5. DM patients with no muscle involvement
6. Patients with life expectancy of less than three months
7. Patients with severe forms of DM and PM: pharyngeal, cardiac or pulmonary involvement
8. Patients without conventional treatments as first-line therapy: prednisone 1 mg/Kg daily Methotrexate 15 mg per week)
9. Patients whose muscle strength is responsive to conventional therapy, i.e. with an improvement of at least 18 points of their BMRC index at baseline compared to the beginning of the run-in period
10. Patients with a BMRC index of less than 32 or more than 64
11. Patients having received a bolus of methylprednisone within three months prior to study entry
12. Patients with a known allergy to one of the ingredients of the IVIg test product
13. Patients with decompensated cardiac insufficiency or any other inter-current condition that may alter the study conduct
14. Patients with positive Coomb's test at baseline

Recruitment start date

21/09/2006

Recruitment end date

06/09/2011

Locations

Countries of recruitment

Austria, Czech Republic, France, Germany, Hungary, Italy, Mexico

Trial participating centre

ORFAGEN,
Toulouse Cedex 1
31 035
France

Sponsor information

Organisation

Orfagen (France)

Sponsor details

CRDPF - LANGLADE
3
avenue Hubert Curien
BP 13562
Toulouse
31035
France

Sponsor type

Industry

Website

http://www.orfagen.com

Funders

Funder type

Industry

Funder name

Orfagen (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes