|- candidate number||25622|
|- NTR Number||NTR6160|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||1-dec-2016|
|- Secondary IDs||ABR: NL 58747 EudraCT: 2016-004766-26|
|- Public Title||IMMEDIATE study|
|- Scientific Title||Intravenous immunoglobulins as early treatment in newly diagnosed idiopathic inflammatory myopathies (IMMEDIATE):
a pilot study|
|- hypothesis||intravenous immunoglobulins will induce a fast and effective response in patients with newly diagnosed idiopathic inflammatory myopathies. Also, the treatment will be generally safe. Furthermore, this pilot study will show feasibility with respect to a future phase 3 study.|
|- Healt Condition(s) or Problem(s) studied||Neuromuscular diseases, Auto-immune diseases|
|- Inclusion criteria||• Adult patients (age ≥ 18 years)|
• Treatment naïve patients
• Subacute-onset of disease (disease duration of ≤ 9 months)
• 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 Polymyositis/overlap myositis/antisynthetase syndrome
o Immune-mediated necrotizing myopathy
|- Exclusion criteria||• IVIg treatment related:|
o Subjects who have received clinical relevant immunosuppressive medication (e.g. plasmapheresis, biologicals, immune therapy etc.) within the last 6 months
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).
• Lack of informed consent (IC)
|- mec approval received||no|
|- multicenter trial||yes|
|- control||Not applicable|
|- Type||Single arm|
|- planned startdate ||16-jan-2017|
|- planned closingdate||16-sep-2017|
|- Target number of participants||20|
|- Interventions||Study subjects will be treated with intravenous immunoglobulin (Privigen®). Initial dose of IVIg is 2 g/kg over 2-4 days, followed by 3 infusions of 1 g/kg on 1-2 days every 3 weeks |
|- Primary outcome||The primary objective is to determine the number of participants with clinical significant improvement at 9 weeks after start of IVIg treatment. |
|- Secondary outcome||Efficacy of IVIg |
1. Time to improvement
2. Significant improvement on each of the 6 Core Set Measures as defined by the International Myositis Assessment & Clinical Studies (IMACS) group.
3. Changes in Amsterdam Linear Disability Scale (ALDS)
4. Changes in Modified Rankin Scale (MRS)
5. Improvement of dysphagia (if present)
6. The number of participants with significant decrease of abnormalities of muscles and fascia on MRI
7. The number of patients with significant change of size and echo density of muscles and fascia on ultrasound
8. Changes in the B-cell repertoire after IVIg treatment
Safety of IVIg
1. The number of detoriating patients needing rescue therapy
2. The number of serious adverse events
Feasibility of a future trial
3. Process: recruitment potential
4. Resources: time and budget estimation
5. Management: exploration of organizational issues
|- Timepoints||primary: after 9 weeks treatment|
- efficacy: after 9 weeks treatment
- safety: during the total duration of the study
- feasibility: end of the study
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES||MD J. Lim|
|- CONTACT for SCIENTIFIC QUERIES||MD PhD A.J. van der Kooi|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Department of Neurology|
(Source(s) of Monetary or Material Support)
|- Brief summary||Rationale: |
Idiopathic inflammatory myopathies, inclusion body myositis excluded, are a group of treatable auto-immune disorders. Due to insufficient efficacy or side-effects of corticosteroids, additional immunosuppressive treatment is often needed. Clinical outcome is often disappointing, with many patients having a polyphasic and chronic clinical course. Relative under treatment in the first period resulting in irreversible damage, is thought to contribute to this. While not yet investigated, there are suggestions that early treatment with intravenous immunoglobulins might induce a fast response. We hypothesize that the use of early IVIg leads to fast improvement in newly diagnosed patients.
Explore efficacy, safety and feasibility (with respect to a future trial) of early treatment with intravenous immunoglobulins for patients with idiopathic inflammatory myopathies.
Investigator initiated, multicenter pilot study with an uncontrolled pre/posttest design.
Twenty newly-diagnosed, treatment-naïve adult patients with idiopathic inflammatory myopathies (except inclusion body myositis).
Patients will be given a starting dose of intravenous immunoglobulins 2 gr/kg in 2-4 days and three maintenance treatments of 1 gr/kg thereafter every three weeks.
Main study parameters/endpoints:
The number of patients with clinical significant improvement, defined as ≥40% 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.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Structured risk analysis shows a moderate risk for patients.
• Side effects: treatment with intravenous immunoglobulins may lead to mild infusion reactions and rarely to serious adverse events such as thrombo-embolic events or hemolysis.
• Possible, temporary undertreatment: the uncertainty regarding efficacy of intravenous immunoglobulins may cause undertreatment in the first 9 week. However, we consider this temporary and adequately manageable with escape medication (consisting of standard corticosteroid therapy).
• Additional study related procedures: follow-up ancillary investigations (MRI, ultrasound, and laboratory investigations) and clinical visits for infusion of intravenous immunoglobulin are considered a minor inconvenience to study participants.
• Beneficial side effect profile compared to standard treatment with corticosteroids.
• Faster and greater total clinical improvement compared to standard treatment with corticosteroids.
|- Main changes (audit trail)|
|- RECORD||1-dec-2016 - 12-feb-2017|