E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic DM and PM with insufficiently improved muscle strength under conventional therapy (Glucocorticosteroids associated with immunosuppressors). |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
To assess the overall safety profile of the IVIg product in DM and PM patients |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
period I: double blind; period II: open |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |