Intravenous immunoglobulin and prednisone vs. prednisone in newly diagnosed myositis: a double blind randomized clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Amsterdam UMC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Immune System Diseases [C20]

Trial duration

10 Oct 2024 → ongoing

Decision date (initial)

2024-10-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-516057-42-00

EudraCT number

2020-001710-37

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

The main objective of this trial is to examine whether the addition of early administered IVIg to standard therapy with prednisone in patients with newly diagnosed myositis leads to an improved clinical response after 12 weeks, compared with prednisone and placebo.

Secondary objectives 4

1. Secondary objective of this trial is to examine whether the intervention leads to a shorter time to improvement.
2. Secondary objective of this trial is to examine whether the intervention leads to sustained positive effects on health-related quality of life (HR-QoL)
3. Secondary objective of this trial is to examine whether the intervention leads to sustained positive effects on physical activity and fatigue.
4. Secondary objective of this trial is to examine whether the intervention leads to sustained positive effects on muscle MRI and blood biomarkers.

Conditions and MedDRA coding

Idiopathic inflammatory myopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Adult patients (≥ 18 years)
2. IIM diagnosis accordiging to diagnostic criteria: - dermatomyositis, - antisynthetase syndrome, - Immune mediated necrotizing myopathy, - overlap/non-specific myositis, including polymyositis.
3. Disease duration <12 months
4. Minimal disability defined as at least 10% loss on Manual Muscle Testing (MMT) and abnormal scores on two other Core Set Measures (CSMs) of the international Myositis Assessment and Clinical Studies (IMACS) group
5. Signed informed consent

Exclusion criteria 5

1. Severe muscle weakness (i.e. bedridden, not able to walk, severe dysphagia requiring a nasogastric tube, or symptomatic respiratory muscle weakness (respiratory symptoms in combination with a forced vital capacity below 50% of predicted in upright position)) necessitating more intensive treatment than standard glucocorticoids.
2. A known malignancy, which is likely to interfere with outcome assessment.
3. Related to IVIg: o History of thrombotic episodes within 10 years prior to enrolment o Known allergic reactions or other severe reactions to any blood-derived product o Known IgA deficiency and IgA serum antibodies o Pregnancy or trying to conceive o Use of nephrotoxic medication
4. Conditions that are likely to interfere with: o Compliance (legally incompetent and/or incapacitated patients are excluded), or, o Evaluation of efficacy (e.g. due to severe pre-existing disability as a result of any disease other than myositis or due to a language barrier)
5. Immunosuppressive medication or immunomodulatory treatment within the last 3 months (e.g. azathioprine, methotrexate, mycophenolate mofetil, tacrolimus, cyclophosphamide, cyclosporine, IVIg, biologicals, Janus kinase inhibitors, plasmapheresis). Exceptions to abovementioned exclusion criteria: • Patients are eligible for inclusion if there is no clinical evident response (as carefully judged by the treating physician at a screening visit) to prior treatment with: • High dosed glucocorticoids, such as dexamethasone (e.g. 40 mg per day up to 4 days) or intravenous methylprednisolone (e.g. 1000 mg daily for three days), within 1 week prior to screening visit. • Daily dosed prednisone 1 mg/kg, or equivalent, used for up to 2 weeks prior to screening visit. • Treatment with biologicals or other immunosuppressive or immunomodulatory treatment when meeting all of the following criteria: o Stable dose for the last 6 months o The biological or other immunosuppressive or immunomodulatory treatment has been approved for a non-muscular condition (e.g. hematological condition, eczema) o The biological or other immunosuppressive or immunomodulatory treatment is not known to induce inflammatory myopathy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. treatment response at 12 weeks, measured by 'total improvement score'

Secondary endpoints 5

1. Health related quality of life (HR-QoL) is measured by EQ-5D.
2. Physical functioning is measured by accelerometry.
3. Biomarker (imaging): assess the presence of muscle edema as a marker of disease activity by whole body muscle MRI
4. Biomarker (blood): interferon biomakers (CXCL-10, galectin-9 and Siglec-1)
5. IgG blood levels

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Amsterdam UMC

Sponsor organisation

Stichting Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Stichting Amsterdam UMC

Contact name

J. Raaphorst

Public contact point

Organisation

Stichting Amsterdam UMC

Contact name

J. Raaphorst

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications