Evaluation of Intravenous Human Normal Immunoglobulin and Prednisone Versus Prednisone Alone in Newly Diagnosed Idiopathic Inflammatory Myopathy
- Trial ID
- 2024-516057-42-00
- Sponsor
- Amsterdam UMC Stichting
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate whether the addition of early administered **intravenous immunoglobulin (IVIg)** to standard therapy with prednisone in patients with newly diagnosed **idiopathic inflammatory myopathy** results in an improved clinical response after 12 weeks, compared with prednisone and placebo. This is clinically relevant as it may enhance treatment efficacy and patient outcomes in managing this condition.
Secondary objectives include examining whether the intervention leads to:
- A shorter time to clinical improvement.
- Sustained positive effects on health-related quality of life (HR-QoL).
- Sustained positive effects on physical activity and fatigue.
- Sustained positive effects on muscle MRI and blood biomarkers.
Participants
The clinical trial involves participants diagnosed with **idiopathic inflammatory myopathy**, specifically targeting adult patients aged 18 years and older. Both male and female subjects are included, with no vulnerable populations selected. The study population comprises individuals with a disease duration of less than 12 months, who exhibit minimal disability as defined by at least a 10% loss on Manual Muscle Testing and abnormal scores on two other Core Set Measures of the international Myositis Assessment and Clinical Studies group. Participants are required to have a confirmed diagnosis of dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myopathy, or overlap/non-specific myositis, including polymyositis. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on these criteria, and all participants have provided signed informed consent. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of early administered intravenous immunoglobulin (IVIg) in combination with prednisone compared to prednisone and placebo in patients with newly diagnosed **idiopathic inflammatory myopathy**. This is a phase 4, double-blind, randomized, placebo-controlled trial. The trial aims to determine if the addition of IVIg leads to an improved clinical response after 12 weeks. The study is expected to run from September 13, 2021, to September 13, 2025.
Participants will be randomly assigned to receive either the test product, **human normal immunoglobulin**, or a placebo, both administered via intravenous infusion. The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and collect data, and a final end-of-study visit to assess the primary and secondary endpoints. The primary endpoint is the treatment response at 12 weeks, measured by the 'total improvement score'. Secondary endpoints include health-related quality of life, physical functioning, and various biomarkers.
Participants are expected to be involved in the study for a maximum treatment period of 3 months. Inclusion criteria require participants to be adults aged 18 years or older, with a diagnosis of idiopathic inflammatory myopathy according to specific diagnostic criteria, and a disease duration of less than 12 months. Participants must also demonstrate minimal disability and provide signed informed consent. Conditions that may lead to early termination from the study include non-compliance with the study protocol or the occurrence of adverse events that compromise participant safety.
Treatment
The clinical trial involves the administration of two primary treatments. The first treatment is **Nanogam**, a **human normal immunoglobulin** solution for infusion, produced by Prothya Biosolutions Netherlands B.V. This experimental medication is administered via **intravenous administration**. The pharmaceutical form is a solution for infusion with a concentration of 100 mg/ml. The maximum daily dose is 80 grams, with a total maximum dose of 180 grams over a treatment period of up to 3 weeks. The active substance is derived from blood, classified as a structurally diverse substance. This treatment is being evaluated for its efficacy in combination with standard therapy in patients with newly diagnosed myositis.
The second treatment used in the trial is **Natriumchloride 0.9% m/v**, a **sodium chloride** solution for infusion, manufactured by Baxter B.V. This solution serves as a placebo in the study. It is also administered intravenously, with a pharmaceutical form of a solution for infusion. The maximum daily dose is 800 ml, and the total maximum dose is 1800 ml over a treatment period of up to 3 weeks. Sodium chloride is a chemically derived substance, and its role in the trial is to provide a control for evaluating the efficacy of the experimental treatment.
Both treatments are administered under controlled conditions, with participant compliance monitored throughout the trial. The trial aims to assess the clinical response of patients receiving the experimental treatment in combination with standard therapy compared to those receiving standard therapy and placebo. The study is conducted in a double-blind, randomized manner to ensure the reliability and validity of the results.
Efficacy
Efficacy in this clinical trial will be assessed through a combination of primary and secondary endpoints. The primary endpoint is the treatment response at 12 weeks, which will be measured by the 'total improvement score'. This score is designed to evaluate the overall clinical response in patients with newly diagnosed **myositis**. Secondary endpoints include several measures to provide a comprehensive assessment of efficacy. Health-related quality of life (HR-QoL) will be evaluated using the EQ-5D instrument, while physical functioning will be assessed through accelerometry. Biomarkers will also play a crucial role in efficacy assessment. Imaging biomarkers will involve the use of whole-body muscle MRI to detect muscle edema, serving as a marker of disease activity. Blood biomarkers will include the measurement of interferon biomarkers such as CXCL-10, galectin-9, and Siglec-1, as well as IgG blood levels.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Adult patients (≥ 18 years)
- IIM diagnosis accordiging to diagnostic criteria: - dermatomyositis, - antisynthetase syndrome, - Immune mediated necrotizing myopathy, - overlap/non-specific myositis, including polymyositis.
- 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
- Signed informed consent
Exclusion Criteria
- 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.
- A known malignancy, which is likely to interfere with outcome assessment.
- 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
- 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)
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Not Recruiting | 13 Sept 2021 | — |
| Netherlands | — | — | 48 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Natriumchloride 0,9 % m/v, oplossing voor infusie | Placebo | OPLOSSING VOOR INFUSIE | INTRAVENOUS ADMINISTRATION | 800 | 3 | PRD374180 |
Nanogam 100 mg/ml oplossing voor infusie | Test | OPLOSSING VOOR INFUSIE | INTRAVENOUS ADMINISTRATION | 80 | 3 | PRD4800147 |