Efficacy and safety of a human normal immunoglobulin product for intravenous administration (IVIg) in the treatment of dermatomyositis (DM) and polymyositis (PM): prospective, randomised, double-blind, placebo-controlled study

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-002463-88-DE
• Date of registration: 28/12/2005
• Prospective Registration: Yes
• Primary sponsor: Orfagen
• Public title: Efficacy and safety of a human normal immunoglobulin product for intravenous administration (IVIg) in the treatment of dermatomyositis (DM) and polymyositis (PM): prospective, randomised, double-blind, placebo-controlled study
• Scientific title: Efficacy and safety of a human normal immunoglobulin product for intravenous administration (IVIg) in the treatment of dermatomyositis (DM) and polymyositis (PM): prospective, randomised, double-blind, placebo-controlled study
• Date of first enrolment: 18/07/2006
• Target sample size: 44
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002463-88
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: period I: double blind; period II: open If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Czech Republic, Germany, Hungary, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female patients of at least 18 years of age

- Patients fulfilling the diagnostic criteria (definite or probable) of the European Neuro-Muscular Committee (ENMC) for idiopathic DM and PM.

- Patients with an active DM or PM disease who received conventional therapies for at least 14 weeks: prospective or clearly-documented retrospective administration of oral prednisone 1mg/Kg per day for at least 4 weeks, with or without IS, followed by IS at stable dose (methotrexate MTX 15-50 mg per week, or other IS) and prednisone for at least 10 weeks,

OR
Patients with a contra-indication or a major side-effect to prednisone or methotrexate / other IS,

OR
Patients under bitherapy (prednisone and MTX / other IS) with a documented deterioration of their BMRC score, as follows:·
- Of at least 18 points if BMRC at the beginning of the run-in period over 56·
- Of at least 12 points if BMRC at the beginning of the run-in period between 40.5 and 56 included·
- Of at least 8 points if BMRC at the beginning of the run-in period below 40.5,

OR
DM patients under bitherapy (prednisone and MTX / other IS) having a documented deterioration of their cutaneous signs, as follows:
- Cutaneous signs aggravated (score from 0 or 1 to 2)·
- Cutaneous signs of 2 at two consecutive visits,

OR
Patients under bitherapy (prednisone and MTX / other IS) with an onset of visceral involvement (e.g. pharyngeal, pulmonary, cardiac).

- Patients with no significant improvement of muscle strength under conventional therapy, as follows:
- Less of 8 points if BMRC score over 56 at the beginning of the run-in period
- Less of 12 points if BMRC score between 40.5 and 56 at the beginning of the run-in period
- Less of 18 points if BMRC score below 40.5 at the beginning of the run-in period.

- Patients with BMRC index between 24 and 72 at baseline.

- For French centres, patients affiliated to the French Security System.

- Patients able to follow instructions.

- Written informed consent from the patients.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Pregnant women, nursing mothers and women of childbearing potential with no reliable contraception.
- Patients who do not fulfill the ENMC diagnostic criteria (definite or probable) of idiopathic DM and PM.
- Patients with a diagnosis of paraneoplasic DM or PM.
- Juvenile DM and PM (age less than 18 years).
- DM patients with no muscle involvement.
- Patients with life expectancy of less than 3 months.
- Patients whose muscle strength is responsive to conventional therapy, i.e. with the following BMRC 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 of their BMRC index at baseline compared to the beginning of the run-in period if BMRC between 40.5 and 56 included at first run-in period assessment
· 8 points of their BMRC index at baseline compared to the beginning of the run-in period if BMRC over 56 at first run-in period assessment
- Patients with an BMRC index of less than 24 or more than 72.
- Patients having received a bolus of methylprednisone within 3 weeks prior to study entry.
- Patients with a known allergy to one of the ingredients of the IVIg test product.
- Patients with decompensated cardiac insufficiency or any other intercurrent condition that may alter the study conduct.
- Patients with positive Coomb’s test at baseline.
- Patients who refuse to participate in the study.
- Patients who are not able to follow instructions.
- Patients who are protected by the law (guardianship, trusteeship).
- Patients who have participated in a study within the 3 months prior to study run-in period.
- Patients who refuse to give written informed consent.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Idiopathic DM and PM with insufficiently improved muscle strength under conventional therapy (Glucocorticosteroids associated with immunosuppressors).

Intervention(s)

Trade Name: Ig VENA
Product Name: Ig VENA (10g/200mL)
Product Code: L0133
Pharmaceutical Form: Solution for infusion
Current Sponsor code: L0133
Other descriptive name: Human normal immunoglobulin (IVIg)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: To assess the overall safety profile of the IVIg product in DM and PM patients

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

Primary end point(s): Muscle strength intensity, as defined by the BMRC and modified by Cherin (Cherin et al., 1994), which assigns the grades 0 to 11 to indicate the level of muscle power in 8 muscle groups (neck flexors, trapezius, deltoid, biceps, psoas, maximus and medius gluteus, and quadriceps). BMRC index will be determined by an independent physician/physiotherapist masked to treatment allocation and study visits.
Treatment response will be defined as an improvement from baseline of BMRC score at the end of Period I (84 days or earlier in case of significant deterioration) as follows:
- Patients with baseline BMRC score between 24 and 40 included: at least 18 points improvement, i.e. an average improvement of more than 2 grades / muscle group (i.e. from patients having contraction with moving initiation to patients having at least moving in the plan).
- Patients with baseline BMRC score between 40.5 and 56 included: at least 12 points improvement, i.e. an average improvement of at least 1.5 grades / muscle group (i.e. from patients having moving initiation in the plan, to patients having at least moving against gravity).
- Patients with baseline BMRC score between 56.5 and 72 included: at least 8 points improvement, i.e. an average improvement of at least 1 grade / muscle group (i.e. from patients having an incomplete moving against gravity to patients having at least a moving initiation against resistance).
Patients prematurely switched from Period I to Period II for BMRC index aggravation will be considered as non-responders.

Secondary ID(s)

ISRCTN87782942

L00133 IV 301 (ORF)