Add-on Intravenous Immunoglobulins in Early Myositis

NCT05832034 | Active Not Recruiting Phase 2

• 1 other identifier: NL74270.018.20
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

In patients with myositis early immunomodulation by intensive treatment ("hit-early/hit-hard" principle) may induce faster reduction of disease activity and prevent chronic disability. Intravenous immunoglobulin (IVIg) in addition to standard treatment with glucocorticoids may be beneficial for this purpose: add-on IVIg improved symptoms in steroid-resistant myositis, and first-line monotherapy IVIg led to a fast and clinically relevant response in a pilot study in nearly 50% of patients with myositis.

Conditions

Dermatomyositis; Inflammatory Myopathy, Idiopathic; Antisynthetase Syndrome; Immune-Mediated Necrotizing Myopathy; Polymyositis; Myositis

Keywords

Myositis; Inflammatory myopathies; Intravenous immunoglobulins; Early symptomatic; Total Improvement Score

Outcome Measures

Primary Outcomes (1)

• Change in Total Improvement Score (TIS)

  The primary outcome is the Total Improvement Score (TIS) of the myositis response criteria after 12 weeks, measured as the difference of the mean TIS after 12 weeks between intervention and control groups. Total Improvement Score (TIS) is based on 6 validated core set measures (CSMs), which each determine disease activity as defined by the International Myositis Assessment and Clinical Studies (IMACS) group. TIS ranges between 0 and 100 and corresponds to a degree of improvement; higher scores correspond to a greater degree of improvement.

  Week 12

Secondary Outcomes (21)

• Total Improvement Score (IMACS).

  TIS will be assessed at t = 0, and after 4, 8, 12, 26 and 52 weeks

• Moderate improvement proportion

  Examined at week 12

• Time to response (TIS>40 points)

  Will be examined at week 4, 8, 12, 26 and 52 weeks.

• Core set measures (CSM) - physician global activity (PhGA)

  CSMs will be assessed at baseline, week 4, 8, 12, 26 and 52.

• Core set measures (CSM) - patient global activity (PGA)

  CSMs will be assessed at baseline, week 4, 8, 12, 26 and 52.

Study Arms (2)

Add-on IVIg

EXPERIMENTAL

Patients in the intervention arm will be treated with Nanogam® in a dosage of 2 g/kg over 2-5 days, with a maximum of 80 g/day and a total of 180 gram at baseline and after 4 and 8 weeks. Nanogam® contains 100 mg/mL normal human immunoglobulin with a purity of at least 95% IgG and a maximum of 12 microgram/mL IgA, in a solution of water for injections and glucose. The first 30 grams are administered in hospital.

Drug: Immune Globulin Intravenous (Human)

Placebo

PLACEBO COMPARATOR

Patients in the control arm will be treated with placebo infusions, containing sodium chloride 0.9%, at baseline and after 4 and 8 weeks. The first 30 grams are administered at the neurology ward, after 4 and 8 weeks infusions will be administered at home

Drug: Placebo

Interventions

Immune Globulin Intravenous (Human) DRUG

IVIg is 2 g/kg over 2 to 5 days at baseline, followed by 2 g/kg IV in 2 to 5 days after 4 and 8 weeks. The rate of infusion is controlled by means of an infusion pump. The first dosage (30 grams IVIg) will be administered on the neurology ward.

Also known as: Nanogam

Add-on IVIg

Placebo DRUG

Placebo infusions, containing sodium chloride 0.9%, at baseline and after 4 and 8 weeks.

Also known as: Sodium chloride or saline 0.9%

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (≥ 18 years) with IIM, according to diagnostic criteria:
• Dermatomyositis
• Polymyositis
• Anti-synthetase syndrome
• Immune mediated necrotizing myopathy
• Overlap myositis
• Disease duration \< 12 months
• 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 (see 'Primary and secondary outcomes').
• 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 low-dosed prednisone (max 20 mg daily) up to three months prior to screening visit.
• Treatment with biologicals or other immunosuppressive or immunomodulatory treatment when meeting all of the following criteria:
• Stable dose for the last 6 months
• The biological or other immunosuppressive or immunomodulatory treatment has been approved for a non-muscular condition (e.g. hematological condition, eczema)
• The biological or other immunosuppressive or immunomodulatory treatment is not known to induce inflammatory myopathy

You may not qualify if:

• A potentially eligible patient who meets any of the following criteria will be excluded from participation in this study:
• Severe muscle weakness (i.e. bedridden, severe dysphagia requiring a feeding tube, or respiratory muscle weakness (forced vital capacity below 50% of predicted in upright position)) necessitating more intensive treatment than standard glucocorticoids from the start.
• Related to IVIg:
• History of thrombotic episodes within 10 years prior to enrolment
• Known allergic reactions or other severe reactions to any blood-derived product
• Known Immunoglobulin A (IgA) deficiency and IgA serum antibodies
• Pregnancy or trying to conceive
• Use of nephrotoxic medication
• Conditions that are likely to interfere with:
• Compliance (legally incompetent and/or incapacitated patients are excluded), or,
• Evaluation of efficacy (e.g. due to severe pre-existing disability as a result of any other disease than myositis or due to language barrier)
• 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).

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Princess Beatrix Muscle Foundation: collaborator
• Prothya Biosolutions: collaborator

Study Sites (1)

Department of Neurology, Amsterdam UMC, location AMC

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Related Publications (7)

• Oddis CV, Aggarwal R. Treatment in myositis. Nat Rev Rheumatol. 2018 May;14(5):279-289. doi: 10.1038/nrrheum.2018.42. Epub 2018 Mar 29.

  PMID: 29593343 BACKGROUND

• Aggarwal R, Rider LG, Ruperto N, Bayat N, Erman B, Feldman BM, Oddis CV, Amato AA, Chinoy H, Cooper RG, Dastmalchi M, Fiorentino D, Isenberg D, Katz JD, Mammen A, de Visser M, Ytterberg SR, Lundberg IE, Chung L, Danko K, Garcia-De la Torre I, Song YW, Villa L, Rinaldi M, Rockette H, Lachenbruch PA, Miller FW, Vencovsky J; International Myositis Assessment and Clinical Studies Group and the Paediatric Rheumatology International Trials Organisation. 2016 American College of Rheumatology/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis. 2017 May;76(5):792-801. doi: 10.1136/annrheumdis-2017-211400.

  PMID: 28385805 BACKGROUND

• Hoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, Vencovsky J, de Visser M, Hughes RA. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10-12 October 2003, Naarden, The Netherlands. Neuromuscul Disord. 2004 May;14(5):337-45. doi: 10.1016/j.nmd.2004.02.006. No abstract available.

  PMID: 15099594 BACKGROUND

• Dalakas MC, Illa I, Dambrosia JM, Soueidan SA, Stein DP, Otero C, Dinsmore ST, McCrosky S. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med. 1993 Dec 30;329(27):1993-2000. doi: 10.1056/NEJM199312303292704.

  PMID: 8247075 BACKGROUND

• Mecoli CA, Park JK, Alexanderson H, Regardt M, Needham M, de Groot I, Sarver C, Lundberg IE, Shea B, de Visser M, Song YW, Bingham CO 3rd, Christopher-Stine L. Perceptions of Patients, Caregivers, and Healthcare Providers of Idiopathic Inflammatory Myopathies: An International OMERACT Study. J Rheumatol. 2019 Jan;46(1):106-111. doi: 10.3899/jrheum.180353. Epub 2018 Sep 15.

  PMID: 30219767 BACKGROUND

• Malattia C, Damasio MB, Madeo A, Pistorio A, Providenti A, Pederzoli S, Viola S, Buoncompagni A, Mattiuz C, Beltramo A, Consolaro A, Ravelli A, Ruperto N, Picco P, Magnano GM, Martini A. Whole-body MRI in the assessment of disease activity in juvenile dermatomyositis. Ann Rheum Dis. 2014 Jun;73(6):1083-90. doi: 10.1136/annrheumdis-2012-202915. Epub 2013 May 1.

  PMID: 23636654 BACKGROUND

• Lim J, Eftimov F, Verhamme C, Brusse E, Hoogendijk JE, Saris CGJ, Raaphorst J, De Haan RJ, van Schaik IN, Aronica E, de Visser M, van der Kooi AJ. Intravenous immunoglobulins as first-line treatment in idiopathic inflammatory myopathies: a pilot study. Rheumatology (Oxford). 2021 Apr 6;60(4):1784-1792. doi: 10.1093/rheumatology/keaa459.

  PMID: 33099648 BACKGROUND

MeSH Terms

Conditions

Myositis; Dermatomyositis; Antisynthetase syndrome; Polymyositis

Interventions

Immunoglobulins, Intravenous; Sodium Chloride

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Raaphorst, MD, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Home-care nurse preparing study medication will be unblinded. Home-care nurse is not involved in outcome assessment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: April 27, 2023
• Study Start: September 13, 2021
• Primary Completion: September 25, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)