Explore efficacy, safety, and feasibility (of an eventual future phase 3 trial) of intravenous immunoglobulins as treatment for patients with idiopathic inflammatory myopathies.
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The number of patients with clinical significant improvement, defined as *40
points improvement on a continuous, weighted score of 6 core set measures (a
internationally validated and combined outcome measure of the International
Myositis Assessment and Clinical Studies group) after 9 weeks of treatment.
1. Physician Global Activity
2. Patient Global Activity
3. Manual Muscle Testing
4. Health Assessment Questionnaire
5. Muscle enzymes
6. Extra-Muscular Activity
Secondary outcome
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
16. relation between treatment respons and serum IgG
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
Background summary
Idiopathic inflammatory myopathies , IBM 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
or chronic clinical course. Relative under treatment in the first period
resulting in irreversible damage, is thought to contribute to this. While not
yet formally 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,
which may ultimately lead to improved short and long term outcome.
Study objective
Explore efficacy, safety, and feasibility (of an eventual future phase 3 trial)
of intravenous immunoglobulins as treatment for patients with idiopathic
inflammatory myopathies.
Study design
Investigator initiated, multicenter pilot study with an uncontrolled
pre/posttest design.
Intervention
Standaard regimen
- Week 0: IVIg 2g/kg
- Week 3: IVIg 1g/kg
- Week 6: IVIg 1g/kg
- Week 9: IVIg 1g/kg + start standaarbehandeling
Optiona regimen: in case of insufficient respons on evaluation at week 4
- Week 0: IVIg 2g/kg
- Week 3: IVIg 1g/kg
- Week 4: IVIg 1g/kg
- Week 8: IVIg 2g/kg
- Week 9: start standard treatment
Study burden and risks
Structured risk analysis shows a negligable 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. Indeed, extensive experience from comparable patient populations
have shown that IVIg is generally well tolerated. Possible, temporary
undertreatment in the first 9 week in case of IVIg unresponsivity. However, we
consider this as temporary and adequately managable with escape medication
(consisting of standard corticosteroid therapy) and the option to intensify the
maintenance infusion from 1g/kg to 2g/kg. Extra follow-up ancillary
investigations (one MRI, one ultrasound and two times an extra laboratory
sample (70.5 ml per sampling moment, which will be in principle, combined with
a regular laboratory investigation) and clinical visits for infusion of
intravenous immunoglobulin are considered a minor inconvenience to study
participants.
Meibergdreef 9
Amsterdam 1107AZ
NL
Meibergdreef 9
Amsterdam 1107AZ
NL
Listed location countries
Age
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
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 with the exception 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)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004766-26-NL |
| CCMO | NL58747.018.16 |