E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
idiopathic inflammatory myopathies |
|
E.1.1.1 | Medical condition in easily understood language |
auto-immune inflammation/disease of the muscles |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
aim of exploring efficacy of early intravenous immunoglobulin treatment for patients with idiopathic inflammatory myopathies |
|
E.2.2 | Secondary objectives of the trial |
aim of exploring safety of early intravenous immunoglobulin treatment for patients with idiopathic inflammatory myopathies, and feasibility with respect to a future phase 3 trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult patients (age ≥ 18 years)
• Subacute-onset of disease (disease duration of ≤ 9 months) of muscle symptoms.
• Biopsy proven IIMs (see for diagnostic criteria Hoogendijk et al. 2004, note: ASS is considered a separate entity, but new criteria in which it has been included, has yet to be published). o Dermatomyositis o Non-specific myositis/antisynthetase syndrome o Immune-mediated necrotizing myopathy
• Minimal disability of: o MMT score reduction of 10% or lower and, o 2 other of the core set measures score abnormalities defined as: - Physician Global Activity 2 cm or more - Patient Global Activity 2 cm or more - Health Assessment Questionnaire 0.25 or more - Muscle enzymes more than 1.5 times upper limit of normal - Extra-Muscular Activity 2 cm or more
|
|
E.4 | Principal exclusion criteria |
• IVIg treatment related: o Subjects who have received systemic immunosuppressive/immunomodulatory medication within the last 6 months with the execption of prednisone dosed as follows: daily dose of 20mg or lower used for 2 weeks or less no evident clinical response
o history of thrombotic episodes within the 2 years prior to enrolment o known allergic reactions or other severe reactions to any blood-derived product o known IgA deficiency and anti-IgA serum antibodies o pregnancy (wish).
• Conditions that are likely to interfere with: o compliance (legal incompetent and/or incapacitated patients are excluded) or, o evaluation of efficacy (e.g. due to severe pre-existing disability as result of any other disease than IIM or language barrier).
• Lack of informed consent (IC)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The number of patients with clinical significant improvement, defined as ≥40 points improvement on a continuous, weighted score of 6 core set measures (as developed by the International Myositis Assessment and Clinical Studies group) after 9 weeks of treatment. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
9 weeks after start of IVIg treatment |
|
E.5.2 | Secondary end point(s) |
Efficacy of IVIg (measured 9 weeks after treatment) 1. Time to at least moderate improvement on the CIS 2. Minimal improvement (20-40 points) on each of the 6 IMACS CSMs a. Physician Global Activity b. Patient Global Activity c. Manual Muscle Testing d. Health Assessment Questionnaire e. Muscle enzymes f. Extra-Muscular Activity 3. Moderate improvement or more (≥40 points) on each of the 6 IMACS CSMs a. Physician Global Activity b. Patient Global Activity c. Manual Muscle Testing d. Health Assessment Questionnaire e. Muscle enzymes f. Extra-Muscular Activity 4. The number of deterioration patients needing rescue therapy 5. Significant improvement in Academic Medical Center Linear Disability Scale (ALDS) 6. Significant improvement in Modified Rankin Scale (MRS) 7. Significant improvement of dysphagia (if present) on the Amyotrofic Lateral Sclerosis Severity Scale Swallowing (ALSSS-SW) 8. Significant improvement in dynamometric muscle strength 9. Significant improvement on the Rasch modified MRC Sum Score (Rasch-MRC) 10. Significant improvement on the EuroQol Group Health Questionnaire (EQ-5D-5L) 11. The number of participants with significant decrease of T2 weighted (T2)/short tau inversion recovery (STIR) hyperintensity of muscles and fascia on MRI 12. The number of patients with significant change of size and echo intensity of muscles and fascia on ultrasound (US) 13. The number of patients with change of highly expanded B-cell clones 14. RNA and RBM20 expression before and after IVIg treatment 15. Galectin-9 and CXCL10 levels before and after IVIg treatment
Safety of IVIg (measured during the total duration of the study) The number of serious adverse events (SAEs)
Feasibility of a future trial (assessed at end report) 1. Process a. recruitment rate b. retention rate 2. Resources a. Estimation of total time investment b. Estimation of total financial investment 3. Management: a. Potential human/personnel concerns b. Potential data concerns c. Potential logistics concerns
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
efficacy 9 weeks after start IVIg treatment, safety during total duration of the study, feasibility at end reports |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
feasibility with respect to an eventual future phase 3 trial |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
LVLS, or in case of unacceptable preliminary results, defined as: • 100% deterioriation and/or SAEs rate in the first 4 inclusions (≥4 study subjects) • ≥80% deterioriation and/or SAEs rate in the first 5 inclusions (≥4 study subjects) • ≥60% deterioriation and/or SAEs rate in the first 6 inclusions (≥4 study subjects) • ≥50% deterioriation and/or SAEs rate after the first 7 inclusions (≥4 study subjects)
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |