Treatment With add-on IVIg in Myositis Early In the diSease Course May be sUperior to Steroids Alone for Reaching CLinical improvemEnt
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Change in Total Improvement Score (TIS)
研究概览
简要总结
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.
详细描述
Considering the known effects of IVIg in idiopathic inflammatory myopathies (IIM), both as add-on therapy in refractory patients, as well as monotherapy in newly diagnosed IIM, we conducted a phase-2 double-blind placebo-controlled randomized trial to investigate the effect of add-on IVIg in patients with newly diagnosed IIM, who are treated with monotherapy prednisone.
Objective:
The primary aim 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 to prednisone and placebo. Clinical response will be measured as the difference of the mean TIS after 12 weeks between intervention and control groups.
The secondary aims are to examine whether the intervention leads to a shorter time to improvement, and sustained positive effects on health-related quality of life, physical activity and fatigue, and a sustained reduction of muscle MRI abnormalities, as assessed up to 52 weeks.
Following a screening visit at the outpatient clinic, patients will be admitted to the neurology ward of the Amsterdam University Medical Center (AUMC) for the first infusion of study treatment. The remaining study medication will be administered at home, according to routine clinical practice for IVIg treatment in neuromuscular disorders in the Netherlands. A second and third study treatment will be administered at home after 4 and 8 weeks. At baseline and after 4, 8, 12, 26 and 52 weeks outcome assessments will be performed at the outpatient clinic. The outpatient study clinic visits at baseline and after 4, 12, 26 and 52 weeks will be combined with regular outpatient clinic visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Home-care nurse preparing study medication will be unblinded. Home-care nurse is not involved in outcome assessment.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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').
- •Patients are eligible for inclusion if they are treatment-naive, or 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 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) and is not known for its use in idiopathic inflammatory myopathy
- •The biological or other immunosuppressive or immunomodulatory treatment is not known to induce inflammatory myopathy
- •Signed informed consent
排除标准
- •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 loop diuretics
- •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).
研究组 & 干预措施
Add-on IVIg
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.
干预措施: Immune Globulin Intravenous (Human) (Drug)
Placebo
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
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Total Improvement Score (TIS)
时间窗: Baseline and week 12
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.
次要结局
- Core set measures (CSM) - Serum muscle enzyme activities(CSMs will be assessed at baseline, week 4, 8, 12, 26 and 52.)
- Time to response (TIS>40 points)(Will be examined at week 4, 8, 12, 26 and 52 weeks.)
- Total Improvement Score (IMACS).(TIS will be assessed at t = 0, and after 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.)
- Core set measures (CSM) - Manual Muscle Testing (MMT)(CSMs will be assessed at baseline, week 4, 8, 12, 26 and 52.)
- Core set measures (CSM) - Health Assessment Questionnaire (HAQ)(CSMs will be assessed at baseline, week 4, 8, 12, 26 and 52.)
- Patient-Reported Outcome Measures (PROMs) questionnaire - Physical function(At baseline, and after 4, 8, 12, 26 and 52 weeks.)
- Fatigue(At baseline, and after 4, 8, 12, 26 and 52 weeks.)
- Health related quality of life (HR-QoL)(At baseline, and after 4, 8, 12, 26 and 52 weeks.)
- Physical activity(Two consecutive weeks, at baseline, week 4, week 8 and week 26.)
- Mean daily prednisone dosage(Calculated at week 4, 8, 12, 26 and 52.)
- Muscle hyperintensities.(At baseline, and after 12 and 26 weeks.)
- IgG blood levels.(Obtained immediately before, and two weeks after the administration of study medication)
- Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI).(At baseline, and after 4, 8, 12, 26 and 52 weeks.)
- Composite questionnaire on health care use and productivity loss.(At baseline and week 12)
- Core set measures (CSM) - Extramuscular disease activity(CSMs will be assessed at baseline, week 4, 8, 12, 26 and 52.)
- Patient-Reported Outcome Measures (PROMs) questionnaire - Fatigue(At baseline, and after 4, 8, 12, 26 and 52 weeks.)
- Patient-Reported Outcome Measures (PROMs) questionnaire - Pain interference(At baseline, and after 4, 8, 12, 26 and 52 weeks.)
研究者
Joost Raaphorst
Principal Investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)